Viruses

12 pages, 3174 KiB

Open AccessArticle

Impact of Early Pandemic SARS-CoV-2 Lineages Replacement with the Variant of Concern P.1 (Gamma) in Western Bahia, Brazil

by Josilene R. Pinheiro, Esther C. dos Reis, Jéssica P. Farias, Mayanna M. C. Fogaça, Patrícia de S. da Silva, Itana Vivian R. Santana, Ana Luiza S. Rocha, Paloma O. Vidal, Rafael da C. Simões, Wilson B. Luiz, Alexander Birbrair, Renato S. de Aguiar, Renan P. de Souza, Vasco A. de C. Azevedo, Gepoliano Chaves, Aline Belmok, Ricardo Durães-Carvalho, Fernando L. Melo, Bergmann M. Ribeiro and Jaime Henrique Amorim

Viruses 2022, 14(10), 2314; https://doi.org/10.3390/v14102314 - 21 Oct 2022

Cited by 6 | Viewed by 2728

Abstract

Background: The correct understanding of the epidemiological dynamics of COVID-19, caused by the SARS-CoV-2, is essential for formulating public policies of disease containment. Methods: In this study, we constructed a picture of the epidemiological dynamics of COVID-19 in a Brazilian population of almost [...] Read more.

Background: The correct understanding of the epidemiological dynamics of COVID-19, caused by the SARS-CoV-2, is essential for formulating public policies of disease containment. Methods: In this study, we constructed a picture of the epidemiological dynamics of COVID-19 in a Brazilian population of almost 17000 patients in 15 months. We specifically studied the fluctuations of COVID-19 cases and deaths due to COVID-19 over time according to host gender, age, viral load, and genetic variants. Results: As the main results, we observed that the numbers of COVID-19 cases and deaths due to COVID-19 fluctuated over time and that men were the most affected by deaths, as well as those of 60 or more years old. We also observed that individuals between 30- and 44-years old were the most affected by COVID-19 cases. In addition, the viral loads in the patients’ nasopharynx were higher in the early symptomatic period. We found that early pandemic SARS-CoV-2 lineages were replaced by the variant of concern (VOC) P.1 (Gamma) in the second half of the study period, which led to a significant increase in the number of deaths. Conclusions: The results presented in this study are helpful for future formulations of efficient public policies of COVID-19 containment. Full article

(This article belongs to the Special Issue What SARS-CoV-2 Variants Have Taught Us: Evolutionary Challenges of RNA Viruses)

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21 pages, 3776 KiB

Open AccessArticle

Tumor Suppressor p53 Inhibits Hepatitis B Virus Replication by Downregulating HBx via E6AP-Mediated Proteasomal Degradation in Human Hepatocellular Carcinoma Cell Lines

by Ha-Yeon Lim, Jiwoo Han, Hyunyoung Yoon and Kyung Lib Jang

Viruses 2022, 14(10), 2313; https://doi.org/10.3390/v14102313 - 21 Oct 2022

Cited by 8 | Viewed by 2822

Abstract

HBx, a multifunctional regulatory protein, plays an essential role in the replication and pathogenesis of the hepatitis B virus (HBV). In this study, we found that in human hepatoma cells, the tumor suppressor p53 downregulates HBx via ubiquitin-dependent proteasomal degradation. p53 transcriptional activity [...] Read more.

HBx, a multifunctional regulatory protein, plays an essential role in the replication and pathogenesis of the hepatitis B virus (HBV). In this study, we found that in human hepatoma cells, the tumor suppressor p53 downregulates HBx via ubiquitin-dependent proteasomal degradation. p53 transcriptional activity that results from HBV infection was not essential for this effect. This was shown by treatment with a potent p53 inhibitor, pifithrin-α. Instead, we found that p53 facilitated the binding of E6-associated protein (E6AP), which is an E3 ligase, to HBx and induced E6AP-mediated HBx ubiquitination in a ternary complex of p53, E6AP, and HBx. The ability of p53 to induce E6AP-mediated downregulation of HBx and inhibit HBV replication was demonstrated in an in vitro HBV infection system. This study may provide insights into the regulation of HBx and HBV replication, especially with respect to p53 status, which may also help in understanding HBV-associated tumorigenesis in patients. Full article

(This article belongs to the Special Issue Ubiquitin and Ubiquitin-Like Pathways in Viral Infection 2023)

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15 pages, 3708 KiB

Open AccessArticle

Synergistic Immunosuppression of Avian Leukosis Virus Subgroup J and Infectious Bursal Disease Virus Is Responsible for Enhanced Pathogenicity

by Weiguo Chen, Sheng Chen, Yu Nie, Wenxue Li, Hongxin Li, Xinheng Zhang, Feng Chen and Qingmei Xie

Viruses 2022, 14(10), 2312; https://doi.org/10.3390/v14102312 - 21 Oct 2022

Cited by 6 | Viewed by 2090

Abstract

In recent years, superinfections of avian leukosis virus subgroup J (ALV-J) and infectious bursal disease virus (IBDV) have been frequently observed in nature, which has led to the increasing virulence in infected chickens. However, the reason for the enhanced pathogenicity has remained unclear. [...] Read more.

In recent years, superinfections of avian leukosis virus subgroup J (ALV-J) and infectious bursal disease virus (IBDV) have been frequently observed in nature, which has led to the increasing virulence in infected chickens. However, the reason for the enhanced pathogenicity has remained unclear. In this study, we demonstrated an effective candidate model for studying the outcome of superinfections with ALV-J and IBDV in cells and specific-pathogen-free (SPF) chicks. Through in vitro experiments, we found that ALV-J and IBDV can establish the superinfection models and synergistically promote the expression of IL-6, IL-10, IFN-α, and IFN-γ in DF-1 and CEF cells. In vivo, the weight loss, survival rate, and histopathological observations showed that more severe pathogenicity was present in the superinfected chickens. In addition, we found that superinfections of ALV-J and IBDV synergistically increased the viral replication of the two viruses and inflammatory mediator secretions in vitro and in vivo. Moreover, by measuring the immune organ indexes and blood proportions of CD3⁺, CD4⁺, and CD8α⁺ cells, our results showed that the more severe instances of immunosuppression were observed in the superinfected chickens. In the present study, we concluded that the more severe immunosuppression induced by the synergistic viral replication of ALV-J and IBDV is responsible for the enhanced pathogenicity. Full article

(This article belongs to the Special Issue Avian Viral Immunosuppressive Disease)

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11 pages, 729 KiB

Open AccessArticle

Genomic Epidemiology Reveals the Circulation of the Chikungunya Virus East/Central/South African Lineage in Tocantins State, North Brazil

by Ueric José Borges de Souza, Raíssa Nunes dos Santos, Marta Giovanetti, Luiz Carlos Junior Alcantara, Jucimária Dantas Galvão, Franciano Dias Pereira Cardoso, Feliph Cássio Sobrinho Brito, Ana Cláudia Franco, Paulo Michel Roehe, Bergmann Morais Ribeiro, Fernando Rosado Spilki and Fabrício Souza Campos

Viruses 2022, 14(10), 2311; https://doi.org/10.3390/v14102311 - 21 Oct 2022

Cited by 8 | Viewed by 2795

Abstract

The chikungunya virus (CHIKV) is a mosquito-borne virus of the family Togaviridae transmitted to humans by Aedes spp. mosquitoes. In Brazil, imported cases have been reported since June 2014 through two independent introductions, one caused by Asian Lineage in Oiapoque, Amapá state, North [...] Read more.

The chikungunya virus (CHIKV) is a mosquito-borne virus of the family Togaviridae transmitted to humans by Aedes spp. mosquitoes. In Brazil, imported cases have been reported since June 2014 through two independent introductions, one caused by Asian Lineage in Oiapoque, Amapá state, North Region, and another caused by East/Central/South African (ECSA) in Feira de Santana, Bahia state, Northeast Region. Moreover, there is still limited information about the genomic epidemiology of the CHIKV from surveillance studies. The Tocantins state, located in Northern Brazil, reported an increase in the number of CHIKV cases at the end of 2021 and the beginning of 2022. Thus, to better understand the dispersion dynamics of this viral pathogen in the state, we generated 27 near-complete CHIKV genome sequences from four cities, obtained from clinical samples. Our results showed that the newly CHIKV genomes from Tocantins belonged to the ECSA lineage. Phylogenetic reconstruction revealed that Tocantins’ strains formed a single well-supported clade, which appear to be closely related to isolates from the Rio Grande do Norte state (Northeast Brazil) and the Rio de Janeiro state (Southeast Brazil), that experienced an explosive ECSA epidemic between 2016–2019. Mutation analyses showed eleven frequent non-synonymous mutations in the structural and non-structural proteins, indicating the autochthonous transmission of the CHIKV in the state. None of the genomes recovered within the Tocantins samples carry the A226V mutation in the E1 protein associated with increased transmission in A. albopictus. The study presented here highlights the importance of continued genomic surveillance to provide information not only on recording mutations along the viral genome but as a molecular surveillance tool to trace virus spread within the country, to predict events of likely occurrence of new infections, and, as such, contribute to an improved public health service. Full article

(This article belongs to the Special Issue Emerging Viruses 2022: Surveillance, Prevention, Evolution and Control)

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12 pages, 1722 KiB

Open AccessArticle

SARS-CoV-2 from COVID-19 Patients in the Republic of Moldova: Whole-Genome Sequencing Results

by Alexandr Morozov, Vadim Nirca, Anna Victorova, Sven Poppert, Hagen Frickmann, Chiaki Yamada, Melissa A. Kacena, Sergiu Rata and Alexandru Movila

Viruses 2022, 14(10), 2310; https://doi.org/10.3390/v14102310 - 21 Oct 2022

Cited by 1 | Viewed by 2080

Abstract

Since the onset of the COVID-19 pandemic, no viral genome sequences of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been documented from the Republic of Moldova, a developing country geographically located in Eastern Europe between Romania and Ukraine. Here, we report the [...] Read more.

Since the onset of the COVID-19 pandemic, no viral genome sequences of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been documented from the Republic of Moldova, a developing country geographically located in Eastern Europe between Romania and Ukraine. Here, we report the analysis of 96 SARS-CoV-2 sequences from Delta and Omicron variants of the SARS-CoV-2 cases in the Republic of Moldova obtained between August and November 2021 and between January and May 2022. Comparison to global viral sequences showed that among the Delta variant of the SARS-CoV-2, AY.122 (n = 25), followed by AY.4.2.3 (n = 6), AY.4 (n = 5), AY.43 (n = 3), AY.98.1 (n = 3), B.1.617.2 (n = 1), AY.125 (n = 1), AY.54 (n = 1), AY.9 (n = 1), AY.126 (n = 1), and AY.33 (n = 1) were the most frequently found lineages. Furthermore, 10 lineages of the Omicron variant, namely, BA.2 (n = 14), followed by BA.2.9 (n = 10), BA.1 (n = 5), BA.1.1 (n = 5), BA.1.18 (n = 4), BA.1.15.1 (n = 3), BA.1.17.2 (n = 2), BA.1.17 (n = 2), BA.1.15 (n = 1), and BA.2.1 (n = 1) were detected. In addition, we also identified the impact of the military crisis between Russia and Ukraine, when the COVID-19 epidemiological rules collapsed, on the distribution of Delta and Omicron variants in the Republic of Moldova. Additional studies are warranted to characterize further the impact of the war between Russia and Ukraine on the genomic epidemiology of the SARS-CoV-2 in the Republic of Moldova and Eastern Europe. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2)

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18 pages, 1150 KiB

Open AccessReview

Host Combats IBDV Infection at Both Protein and RNA Levels

by Shujun Zhang and Shijun Zheng

Viruses 2022, 14(10), 2309; https://doi.org/10.3390/v14102309 - 21 Oct 2022

Cited by 5 | Viewed by 2371

Abstract

Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by infectious bursal disease virus (IBDV). In recent years, with the emergence of IBDV variants and recombinant strains, IBDV still threatens the poultry industry worldwide. It seems that the [...] Read more.

Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by infectious bursal disease virus (IBDV). In recent years, with the emergence of IBDV variants and recombinant strains, IBDV still threatens the poultry industry worldwide. It seems that the battle between host and IBDV will never end. Thus, it is urgent to develop a more comprehensive and effective strategy for the control of this disease. A better understanding of the mechanisms underlying virus–host interactions would be of help in the development of novel vaccines. Recently, much progress has been made in the understanding of the host response against IBDV infection. If the battle between host and IBDV at the protein level is considered the front line, at the RNA level, it can be taken as a hidden line. The host combats IBDV infection at both the front and hidden lines. Therefore, this review focuses on our current understanding of the host response to IBDV infection at both the protein and RNA levels. Full article

(This article belongs to the Special Issue Avian Viral Immunosuppressive Disease)

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9 pages, 1093 KiB

Open AccessReview

Revisiting Papillomavirus Taxonomy: A Proposal for Updating the Current Classification in Line with Evolutionary Evidence

by Koenraad Van Doorslaer

Viruses 2022, 14(10), 2308; https://doi.org/10.3390/v14102308 - 21 Oct 2022

Cited by 12 | Viewed by 2782

Abstract

Papillomaviruses infect a wide array of animal hosts and are responsible for roughly 5% of all human cancers. Comparative genomics between different virus types belonging to specific taxonomic groupings (e.g., species, and genera) has the potential to illuminate physiological differences between viruses with [...] Read more.

Papillomaviruses infect a wide array of animal hosts and are responsible for roughly 5% of all human cancers. Comparative genomics between different virus types belonging to specific taxonomic groupings (e.g., species, and genera) has the potential to illuminate physiological differences between viruses with different biological outcomes. Likewise, extrapolation of features between related viruses can be very powerful but requires a solid foundation supporting the evolutionary relationships between viruses. The current papillomavirus classification system is based on pairwise sequence identity. However, with the advent of metagenomics as facilitated by high-throughput sequencing and molecular tools of enriching circular DNA molecules using rolling circle amplification, there has been a dramatic increase in the described diversity of this viral family. Not surprisingly, this resulted in a dramatic increase in absolute number of viral types (i.e., sequences sharing <90% L1 gene pairwise identity). Many of these novel viruses are the sole member of a novel species within a novel genus (i.e., singletons), highlighting that we have only scratched the surface of papillomavirus diversity. I will discuss how this increase in observed sequence diversity complicates papillomavirus classification. I will propose a potential solution to these issues by explicitly basing the species and genera classification on the evolutionary history of these viruses based on the core viral proteins (E1, E2, and L1) of papillomaviruses. This strategy means that it is possible that a virus identified as the closest neighbor based on the E1, E2, L1 phylogenetic tree, is not the closest neighbor based on L1 nucleotide identity. In this case, I propose that a virus would be considered a novel type if it shares less than 90% identity with its closest neighbors in the E1, E2, L1 phylogenetic tree. Full article

(This article belongs to the Special Issue Models and Approaches for Studying Papillomavirus Infection, Pathogenesis, and Disease)

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16 pages, 4514 KiB

Open AccessArticle

Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan

by Uroosa Tariq, Jamirah Nazziwa, Sviataslau Sasinovich, Sharaf Ali Shah, Sadaf Naeem, Syed Hani Abidi and Joakim Esbjörnsson

Viruses 2022, 14(10), 2307; https://doi.org/10.3390/v14102307 - 20 Oct 2022

Cited by 2 | Viewed by 2252

Abstract

(1) Background: HIV-1 sub-subtype A1 is common in parts of Africa, Russia, former Soviet Union countries, and Eastern Europe. In Pakistan, sub-subtype A1 is the predominant HIV-1 subtype. Preliminary evidence suggests that distinct strains of HIV-1 sub-subtype A1 are circulating in Pakistan; however, [...] Read more.

(1) Background: HIV-1 sub-subtype A1 is common in parts of Africa, Russia, former Soviet Union countries, and Eastern Europe. In Pakistan, sub-subtype A1 is the predominant HIV-1 subtype. Preliminary evidence suggests that distinct strains of HIV-1 sub-subtype A1 are circulating in Pakistan; however, an in-depth molecular phylogenetic characterization of HIV-1 sub-subtype A1 strains in Pakistan have not been presented. We performed a detailed characterization of the HIV-1 sub-subtype A1 epidemic in Pakistan using state-of-the-art molecular epidemiology and phylodynamics. (2) Methods: A total of 143 HIV-1 sub-subtype A1 gag sequences, including 61 sequences generated specifically for this study from PLHIVs part of our cohort, representing all sub-subtype A1 gag sequences from Pakistan, were analyzed. Maximum-likelihood phylogenetic cluster analysis was used to determine the relationship between Pakistani sub-subtype A1 strains and pandemic sub-subtype A1 strains. Furthermore, we used signature variation, charge distribution, selection pressures, and epitope prediction analyses to characterize variations unique to Pakistani HIV-1 strains and establish the association between signature variations and Gag epitope profile. (3) Results: The HIV-1 sub-subtype A1 sequences from Pakistan formed three main clusters: two that clustered with Kenyan sequences (7 and 10 sequences, respectively) and one that formed a Pakistan-specific cluster of 123 sequences that were much less related to other sub-subtype A1 sequences available in the database. The sequences in the Pakistan-specific cluster and the Kenyan reference strains exhibited several signature variations, especially at amino acid positions 312, 319, 331, 372, 373, 383, and 402. Structural protein modeling suggested that amino acid changes in these positions result in alterations of the Gag protein structure as well as in Gag-specific T-cell epitopes. (4) Conclusions: Our results suggest that the majority of the Pakistan HIV-1 sub-subtype A1 strains were unique to Pakistan and with a specific mutation pattern in Gag. Full article

(This article belongs to the Special Issue Population Genomics of Human Viruses)

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19 pages, 3171 KiB

Open AccessArticle

Genetic and Cross Neutralization Analyses of Coxsackievirus A16 Circulating in Taiwan from 1998 to 2021 Suggest Dominant Genotype B1 can Serve as Vaccine Candidate

by Dayna Cheng, Yo-Wei Chiu, Sheng-Wen Huang, Yun-Yin Lien, Chia-Lun Chang, Huey-Pin Tsai, Ya-Fang Wang and Jen-Ren Wang

Viruses 2022, 14(10), 2306; https://doi.org/10.3390/v14102306 - 20 Oct 2022

Cited by 3 | Viewed by 2224

Abstract

Coxsackievirus A16 (CVA16) is well known for causing hand-foot-and-mouth disease (HFMD) and outbreaks were frequently reported in Taiwan in the past twenty years. The epidemiology and genetic variations of CVA16 in Taiwan from 1998 to 2021 were analyzed in this study. CVA16 infections [...] Read more.

Coxsackievirus A16 (CVA16) is well known for causing hand-foot-and-mouth disease (HFMD) and outbreaks were frequently reported in Taiwan in the past twenty years. The epidemiology and genetic variations of CVA16 in Taiwan from 1998 to 2021 were analyzed in this study. CVA16 infections usually occurred in early summer and early winter, and showed increased incidence in 1998, 2000–2003, 2005, 2007–2008, and 2010 in Taiwan. Little or no CVA16 was detected from 2017 to 2021. CVA16 infection was prevalent in patients between 1 to 3 years old. A total of 69 isolates were sequenced. Phylogenetic analysis based on the VP1 region showed that CVA16 subgenotype B1 was dominantly isolated in Taiwan from 1998 to 2019, and B2 was identified only from isolates collected in 1999 and 2000. There was a high frequency of synonymous mutations in the amino acid sequences of the VP1 region among CVA16 isolates, with the exception of position 145 which showed positive selection. The recombination analysis of the whole genome of CVA16 isolates indicated that the 5′-untranslated region and the non-structural protein region of CVA16 subgenotype B1 were recombined with Coxsackievirus A4 (CVA4) and enterovirus A71 (EVA71) genotype A, respectively. The recombination pattern of subgenotype B2 was similar to B1, however, the 3D region was similar to EVA71 genotype B. Cross-neutralization among CVA16 showed that mouse antisera from various subgenotypes viruses can cross-neutralize different genotype with high neutralizing antibody titers. These results suggest that the dominant CVA16 genotype B1 can serve as a vaccine candidate for CVA16. Full article

(This article belongs to the Special Issue Antivirals and Vaccines for Enterovirus)

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21 pages, 1478 KiB

Open AccessArticle

Diversity and Ecology of Caudoviricetes Phages with Genome Terminal Repeats in Fecal Metagenomes from Four Dutch Cohorts

by Anastasia Gulyaeva, Sanzhima Garmaeva, Alexander Kurilshikov, Arnau Vich Vila, Niels P. Riksen, Mihai G. Netea, Rinse K. Weersma, Jingyuan Fu and Alexandra Zhernakova

Viruses 2022, 14(10), 2305; https://doi.org/10.3390/v14102305 - 20 Oct 2022

Cited by 5 | Viewed by 4003

Abstract

The human gut harbors numerous viruses infecting the human host, microbes, and other inhabitants of the gastrointestinal tract. Most of these viruses remain undiscovered, and their influence on human health is unknown. Here, we characterize viral genomes in gut metagenomic data from 1950 [...] Read more.

The human gut harbors numerous viruses infecting the human host, microbes, and other inhabitants of the gastrointestinal tract. Most of these viruses remain undiscovered, and their influence on human health is unknown. Here, we characterize viral genomes in gut metagenomic data from 1950 individuals from four population and patient cohorts. We focus on a subset of viruses that is highly abundant in the gut, remains largely uncharacterized, and allows confident complete genome identification—phages that belong to the class Caudoviricetes and possess genome terminal repeats. We detect 1899 species-level units belonging to this subset, 19% of which do not have complete representative genomes in major public gut virome databases. These units display diverse genomic features, are predicted to infect a wide range of microbial hosts, and on average account for <1% of metagenomic reads. Analysis of longitudinal data from 338 individuals shows that the composition of this fraction of the virome remained relatively stable over a period of 4 years. We also demonstrate that 54 species-level units are highly prevalent (detected in >5% of individuals in a cohort). Finally, we find 34 associations between highly prevalent phages and human phenotypes, 24 of which can be explained by the relative abundance of potential hosts. Full article

(This article belongs to the Section Bacterial Viruses)

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12 pages, 1999 KiB

Open AccessArticle

Cloning, Exogenous Expression and Function Analysis of Interferon–γ from Gadus macrocephalus

by Jielan Jiang, Jie Gu, Aijun Zhan, Mingguang Mao, Yumeng Liu, Haishan Wang and Yunxiang Mao

Viruses 2022, 14(10), 2304; https://doi.org/10.3390/v14102304 - 20 Oct 2022

Cited by 2 | Viewed by 2128

Abstract

Interferon γ (IFN–γ) is now considered to be one of the key molecules in the regulation of innate and adaptive immunity. The function of IFN–γ is best described in humans, but less of IFN–γ in fish species has been described at protein level. [...] Read more.

Interferon γ (IFN–γ) is now considered to be one of the key molecules in the regulation of innate and adaptive immunity. The function of IFN–γ is best described in humans, but less of IFN–γ in fish species has been described at protein level. In the present study, IFN–γ from Gadus macrocephalus (GmIFN–γ) has been examined in terms of bioinformatics, prokaryotic expression, yeast expression, antiviral activity and immune regulatory function. The cDNA of GmIFN–γ contains an open reading frame of 570 nucleotides, coding 189 amino acids. The mature protein contains a nuclear localization signal motif and an obvious IFN–γ signature sequence at the C-terminal. GmIFN–γ is very similar to that of Atlantic cod, with homology up to 89.89%, but less than 32% to other species. GmIFN–γ can be detected in the gills, spleen, intestine, brain and kidney. Interestingly, during early development, a strong signal of GmIFN–γ was not detected until 40 days post hatching. Prokaryotic expression plasmid pET–32a–GmIFN–γ was constructed, and the expression products in BL21 were confirmed by Mass Spectrometry. Meanwhile, the plasmid pGAPZA–GmIFN–γ with Myc tag was constructed and transmitted into Pichia pastoris yeast GS115, and the products were tested using Western blot. The purified GmIFN–γ from either BL21 or yeast has a strong antivirus (Spring viremia of carp virus) effect. The vector of pcDNA3.1–GmIFN–γ was expressed in EPC cell lines; high transcript levels of MHC class I chain-related protein A (MICA) gene were detected; and the exogenous GmIFN–γ protein could also induce MICA expression, indicating that GmIFN–γ could stimulate immune response. The yeast GS115 with GmIFN–γ protein, which is an inclusion body, was given to zebrafish orally, and the transcript of zebrafish IFN–γ was upregulated significantly; however, genes of the interferon type–I signal pathway were not well stimulated. Full article

(This article belongs to the Special Issue Fish Antiviral Immunity)

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21 pages, 2349 KiB

Open AccessArticle

Characterization of Grapevine Fanleaf Virus Isolates in ‘Chardonnay’ Vines Exhibiting Severe and Mild Symptoms in Two Vineyards

by Julie Kubina, Jean-Michel Hily, Pierre Mustin, Véronique Komar, Shahinez Garcia, Isabelle Rachel Martin, Nils Poulicard, Amandine Velt, Véronique Bonnet, Laurence Mercier, Olivier Lemaire and Emmanuelle Vigne

Viruses 2022, 14(10), 2303; https://doi.org/10.3390/v14102303 - 20 Oct 2022

Cited by 4 | Viewed by 2781

Abstract

Fanleaf degeneration is a complex viral disease of Vitis spp. that detrimentally impacts fruit yield and reduces the productive lifespan of most vineyards worldwide. In France, its main causal agent is grapevine fanleaf virus (GFLV). In the past, field experiments were conducted to [...] Read more.

Fanleaf degeneration is a complex viral disease of Vitis spp. that detrimentally impacts fruit yield and reduces the productive lifespan of most vineyards worldwide. In France, its main causal agent is grapevine fanleaf virus (GFLV). In the past, field experiments were conducted to explore cross-protection as a management strategy of fanleaf degeneration, but results were unsatisfactory because the mild virus strain negatively impacted fruit yield. In order to select new mild GFLV isolates, we examined two old ‘Chardonnay’ parcels harbouring vines with distinct phenotypes. Symptoms and agronomic performances were monitored over the four-year study on 21 individual vines that were classified into three categories: asymptomatic GFLV-free vines, GFLV-infected vines severely diseased and GFLV-infected vines displaying mild symptoms. The complete coding genomic sequences of GFLV isolates in infected vines was determined by high-throughput sequencing. Most grapevines were infected with multiple genetically divergent variants. While no specific molecular features were apparent for GFLV isolates from vines displaying mild symptoms, a genetic differentiation of GFLV populations depending on the vineyard parcel was observed. The mild symptomatic grapevines identified during this study were established in a greenhouse to recover GFLV variants of potential interest for cross-protection studies. Full article

(This article belongs to the Special Issue A Tribute to Giovanni P. Martelli)

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13 pages, 1429 KiB

Open AccessReview

Host Cell Receptors Implicated in the Cellular Tropism of BVDV

by Shuhui Qi, Lijing Wo, Chao Sun, Juan Zhang, Quanhai Pang and Xin Yin

Viruses 2022, 14(10), 2302; https://doi.org/10.3390/v14102302 - 20 Oct 2022

Cited by 3 | Viewed by 4345

Abstract

Bovine viral diarrhea virus (BVDV) is one of the most hazardous viruses, which causes huge economic losses in the cattle industry around the world. In recent years, there has been a continuous increase in the diversity of pestivirus worldwide. As a member of [...] Read more.

Bovine viral diarrhea virus (BVDV) is one of the most hazardous viruses, which causes huge economic losses in the cattle industry around the world. In recent years, there has been a continuous increase in the diversity of pestivirus worldwide. As a member of the genus Pestivirus in the Flaviviridae family, BVDV has a wide range of host animals including cattle, goat, sheep, pig, camel and other cloven-hoofed animals, and it has multi-tissue tropism as well. The recognition of their permissive cells by viruses via interaction with the cellular receptors is a prerequisite for successful infection. So far, little is known about the cellular receptors essential for BVDV entry and their detailed functions during BVDV infection. Thus, discovery of the cellular receptors involved in the entry of BVDV and other pestiviruses is significant for development of the novel intervention. The viral envelope glycoprotein E^rns and E2 are crucial determinants of the cellular tropism of BVDV. The cellular proteins bound with E^rns and E2 potentially participate in BVDV entry, and their abundance might determine the cellular tropism of BVDV. Here, we summarize current knowledge regarding the cellular molecules have been described for BVDV entry, such as, complement regulatory protein 46 (CD46), heparan sulfate (HS), the low-density lipoprotein (LDL) receptor, and a disintegrin and metalloproteinase 17 (ADAM17). Furthermore, we focus on their implications of the recently identified cellular receptors for pestiviruses in BVDV life cycle. This knowledge provides a theoretical basis for BVDV prevention and treatment by targeting the cellular receptors essential for BVDV infection. Full article

(This article belongs to the Special Issue Viral-Host Cell Interactions of Animal Viruses)

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19 pages, 2746 KiB

Open AccessReview

Two Years of Genomic Surveillance in Belgium during the SARS-CoV-2 Pandemic to Attain Country-Wide Coverage and Monitor the Introduction and Spread of Emerging Variants

by Lize Cuypers, Simon Dellicour, Samuel L. Hong, Barney I. Potter, Bruno Verhasselt, Nick Vereecke, Laurens Lambrechts, Keith Durkin, Vincent Bours, Sofieke Klamer, Guillaume Bayon-Vicente, Carl Vael, Kevin K. Ariën, Ricardo De Mendonca, Oriane Soetens, Charlotte Michel, Bertrand Bearzatto, Reinout Naesens, Jeremie Gras, Anne Vankeerberghen, Veerle Matheeussen, Geert Martens, Dagmar Obbels, Ann Lemmens, Bea Van den Poel, Ellen Van Even, Klara De Rauw, Luc Waumans, Marijke Reynders, Jonathan Degosserie, Piet Maes, Emmanuel André and Guy Baele Show full author list Hide full author list

Viruses 2022, 14(10), 2301; https://doi.org/10.3390/v14102301 - 20 Oct 2022

Cited by 10 | Viewed by 3680

Abstract

An adequate SARS-CoV-2 genomic surveillance strategy has proven to be essential for countries to obtain a thorough understanding of the variants and lineages being imported and successfully established within their borders. During 2020, genomic surveillance in Belgium was not structurally implemented but performed [...] Read more.

An adequate SARS-CoV-2 genomic surveillance strategy has proven to be essential for countries to obtain a thorough understanding of the variants and lineages being imported and successfully established within their borders. During 2020, genomic surveillance in Belgium was not structurally implemented but performed by individual research laboratories that had to acquire the necessary funds themselves to perform this important task. At the start of 2021, a nationwide genomic surveillance consortium was established in Belgium to markedly increase the country’s genomic sequencing efforts (both in terms of intensity and representativeness), to perform quality control among participating laboratories, and to enable coordination and collaboration of research projects and publications. We here discuss the genomic surveillance efforts in Belgium before and after the establishment of its genomic sequencing consortium, provide an overview of the specifics of the consortium, and explore more details regarding the scientific studies that have been published as a result of the increased number of Belgian SARS-CoV-2 genomes that have become available. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)

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14 pages, 4423 KiB

Open AccessArticle

Novel Bacillus-Infecting Bacteriophage B13—The Founding Member of the Proposed New Genus Bunatrivirus

by Olesya A. Kazantseva, Emma G. Piligrimova and Andrey M. Shadrin

Viruses 2022, 14(10), 2300; https://doi.org/10.3390/v14102300 - 19 Oct 2022

Cited by 7 | Viewed by 2048

Abstract

In this work, we describe a novel temperate bacteriophage, Bacillus phage B13. Bacillus-infecting phages are widespread and abundant, though often overlooked including because of their temperate lifestyle. B13 was isolated from its bacterial host via mitomycin C induction. Its host range was [...] Read more.

In this work, we describe a novel temperate bacteriophage, Bacillus phage B13. Bacillus-infecting phages are widespread and abundant, though often overlooked including because of their temperate lifestyle. B13 was isolated from its bacterial host via mitomycin C induction. Its host range was determined, and its pH and thermal stability were evaluated. The whole genome of B13 was sequenced and annotated. The genome is 36,864 bp long and contains 53 genes. The tail genes of B13 suggest that the phage has a siphovirus morphotype. It was found both in vitro and in silico that the phage uses the 3′-cos DNA packaging strategy, and the phage genome termini were located. Comparative analyses revealed that B13 has no close relatives and should therefore be assigned to a new viral genus, for which we propose the name Bunatrivirus. Full article

(This article belongs to the Section Bacterial Viruses)

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10 pages, 970 KiB

Open AccessArticle

Immune Response after the Fourth Dose of SARS-CoV-2 mRNA Vaccine Compared to Natural Infection in Three Doses’ Vaccinated Solid Organ Transplant Recipients

by Rosalia Busà, Giovanna Russelli, Monica Miele, Maria Concetta Sorrentino, Mariangela Di Bella, Francesca Timoneri, Giuseppina Di Mento, Alessandra Mularoni, Patrizio Vitulo, Pier Giulio Conaldi and Matteo Bulati

Viruses 2022, 14(10), 2299; https://doi.org/10.3390/v14102299 - 19 Oct 2022

Cited by 9 | Viewed by 2409

Abstract

Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants [...] Read more.

Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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11 pages, 3601 KiB

Open AccessArticle

Investigation of the Association between the Energy Metabolism of the Insect Vector Laodelphax striatellus and Rice Stripe Virus (RSV)

by Lu Zhang, Xinyi Li, Yan Chen, Lin Kang, Jiao Zhang, Yao Li and Fang Liu

Viruses 2022, 14(10), 2298; https://doi.org/10.3390/v14102298 - 19 Oct 2022

Viewed by 1857

Abstract

Viruses, as intracellular parasites, rely on the host organism to complete their life cycle. Although over 70% of plant viruses are transmitted by insect vectors, the role of vector energy metabolism on the infection process of insect-borne plant viruses is unclear. In this [...] Read more.

Viruses, as intracellular parasites, rely on the host organism to complete their life cycle. Although over 70% of plant viruses are transmitted by insect vectors, the role of vector energy metabolism on the infection process of insect-borne plant viruses is unclear. In this study, full-length cDNAs of three energy metabolism-related genes (LsATPase, LsMIT13 and LsNADP-ME) were obtained from the small brown planthopper (SBPH, Laodelphax striatellus), which transmits the Rice stripe virus (RSV). Expression levels of LsATPase, LsMIT13 and LsNADP-ME increased by 105%, 1120% and 259%, respectively, due to RSV infection. The repression of LsATPase, LsMIT13 or LsNADP-ME by RNAi had no effect on RSV nucleocapsid protein (NP) transcripts or protein levels. The repression of LsATPase caused a significant increase in LsMIT13 and LsNADP-ME transcript levels by 230% and 217%, respectively, and the repression of LsMIT13 caused a significant increase in LsNADP-ME mRNA levels. These results suggested that the silencing of LsATPase induced compensatory upregulation of LsMIT13 and LsNADP-ME, and silencing LsMIT13 induced compensatory upregulation of LsNADP-ME. Further study indicated that the co-silencing of LsATPase, LsMIT13 and LsNADP-ME in viruliferous SBPHs increased ATP production and RSV loads by 182% and 117%, respectively, as compared with nonviruliferous SBPHs. These findings indicate that SBPH energy metabolism is involved in RSV infection and provide insight into the association between plant viruses and energy metabolism in the insect vector. Full article

(This article belongs to the Special Issue Virus-Vector Interactions)

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17 pages, 5001 KiB

Open AccessArticle

An Unwanted Association: The Threat to Papaya Crops by a Novel Potexvirus in Northwest Argentina

by Dariel Cabrera Mederos, Humberto Debat, Carolina Torres, Orelvis Portal, Margarita Jaramillo Zapata, Verónica Trucco, Ceferino Flores, Claudio Ortiz, Alejandra Badaracco, Luis Acuña, Claudia Nome, Diego Quito-Avila, Nicolas Bejerman, Onias Castellanos Collazo, Aminael Sánchez-Rodríguez and Fabián Giolitti

Viruses 2022, 14(10), 2297; https://doi.org/10.3390/v14102297 - 19 Oct 2022

Cited by 5 | Viewed by 3040

Abstract

An emerging virus isolated from papaya (Carica papaya) crops in northwestern (NW) Argentina was sequenced and characterized using next-generation sequencing. The resulting genome is 6667-nt long and encodes five open reading frames in an arrangement typical of other potexviruses. This virus [...] Read more.

An emerging virus isolated from papaya (Carica papaya) crops in northwestern (NW) Argentina was sequenced and characterized using next-generation sequencing. The resulting genome is 6667-nt long and encodes five open reading frames in an arrangement typical of other potexviruses. This virus appears to be a novel member within the genus Potexvirus. Blast analysis of RNA-dependent RNA polymerase (RdRp) and coat protein (CP) genes showed the highest amino acid sequence identity (67% and 71%, respectively) with pitaya virus X. Based on nucleotide sequence similarity and phylogenetic analysis, the name papaya virus X is proposed for this newly characterized potexvirus that was mechanically transmitted to papaya plants causing chlorotic patches and severe mosaic symptoms. Papaya virus X (PapVX) was found only in the NW region of Argentina. This prevalence could be associated with a recent emergence or adaptation of this virus to papaya in NW Argentina. Full article

(This article belongs to the Special Issue Emerging Fruit and Vegetable Viruses)

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16 pages, 2404 KiB

Open AccessArticle

Evolutionary Pattern Comparisons of the SARS-CoV-2 Delta Variant in Countries/Regions with High and Low Vaccine Coverage

by Jiahao Zhang, Linqian Fan, Hanli Xu, Yuanhui Fu, Xianglei Peng, Yanpeng Zheng, Jiemei Yu and Jinsheng He

Viruses 2022, 14(10), 2296; https://doi.org/10.3390/v14102296 - 19 Oct 2022

Cited by 4 | Viewed by 2151

Abstract

It has been argued that vaccine-breakthrough infections of SARS-CoV-2 would likely accelerate the emergence of novel variants with immune evasion. This study explored the evolutionary patterns of the Delta variant in countries/regions with relatively high and low vaccine coverage based on large-scale sequences. [...] Read more.

It has been argued that vaccine-breakthrough infections of SARS-CoV-2 would likely accelerate the emergence of novel variants with immune evasion. This study explored the evolutionary patterns of the Delta variant in countries/regions with relatively high and low vaccine coverage based on large-scale sequences. Our results showed that (i) the sequences were grouped into two clusters (L and R); the R cluster was dominant, its proportion increased over time and was higher in the high-vaccine-coverage areas; (ii) genetic diversities in the countries/regions with low vaccine coverage were higher than those in the ones with high vaccine coverage; (iii) unique mutations and co-mutations were detected in different countries/regions; in particular, common co-mutations were exhibited in highly occurring frequencies in the areas with high vaccine coverage and presented in increasing frequencies over time in the areas with low vaccine coverage; (iv) five sites on the S protein were under strong positive selection in different countries/regions, with three in non-C to U sites (I95T, G142D and T950N), and the occurring frequencies of I95T in high vaccine coverage areas were higher, while G142D and T950N were potentially immune-pressure-selected sites; and (v) mutation at the N⁶-methyladenosine site 4 on ORF7a (C27527T, P45L) was detected and might be caused by immune pressure. Our study suggested that certain variation differences existed between countries/regions with high and low vaccine coverage, but they were not likely caused by host immune pressure. We inferred that no extra immune pressures on SARS-CoV-2 were generated with high vaccine coverage, and we suggest promoting and strengthening the uptake of the COVID-19 vaccine worldwide, especially in less developed areas. Full article

(This article belongs to the Collection SARS-CoV-2 and COVID-19)

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13 pages, 2037 KiB

Open AccessArticle

Host-Level Susceptibility and IRF1 Expression Influence the Ability of IFN-γ to Inhibit KSHV Infection in B Lymphocytes

by Nedaa Alomari and Jennifer Totonchy

Viruses 2022, 14(10), 2295; https://doi.org/10.3390/v14102295 - 19 Oct 2022

Viewed by 2102

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi’s sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman’s disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, [...] Read more.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi’s sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman’s disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, little is known about the role of host microenvironment in the regulation of KSHV establishment in B cells. In the present study, we demonstrated that IFN-γ has a strong inhibitory effect on KSHV infection but only in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, and display increased levels of IRF1 and STAT1-pY701. The effect of IFN-γ in responsive samples was associated with increased frequencies of germinal center B cells (GCB) and decreased infection of plasma cells, suggesting that IFN-γ-mediated modulation of viral dynamics in GC can inhibit the establishment of KSHV infection. Full article

(This article belongs to the Section Animal Viruses)

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12 pages, 645 KiB

Open AccessArticle

High Prevalence of Undocumented SARS-CoV-2 Infections in the Pediatric Population of the Tyrolean District of Schwaz

by Teresa Harthaller, Wegene Borena, David Bante, Helena Schäfer, Oliver Strallhofer, Thomas Zöggeler, Eva Hochmuth, Luiza Hoch, Annika Rössler, Dorothee von Laer, Janine Kimpel and Barbara Falkensammer

Viruses 2022, 14(10), 2294; https://doi.org/10.3390/v14102294 - 19 Oct 2022

Cited by 2 | Viewed by 1804

Abstract

Complementing the adult seroprevalence data collected at the time of the rapid SARS-CoV-2 mass vaccination in the district of Schwaz in 2021, we set out to establish the seroprevalence of SARS-CoV-2 among the pediatric population of the district. A total of 369 children, [...] Read more.

Complementing the adult seroprevalence data collected at the time of the rapid SARS-CoV-2 mass vaccination in the district of Schwaz in 2021, we set out to establish the seroprevalence of SARS-CoV-2 among the pediatric population of the district. A total of 369 children, mean age 9.9 (SD 3.4), participated in the study, answering a structured questionnaire on the history of SARS-CoV-2 infection, household contacts, symptoms and history of vaccination. We determined binding and neutralizing antibody levels using plasma samples provided. We estimated the overall prevalence of SARS-CoV-2 infection in the general pediatric population at the time of the study using the census data from Statistik Austria and daily reports of officially confirmed cases. Excluding study participants who reported a history of PCR-confirmed infection, the age-standardized seroprevalence of previously unknown SARS-CoV-2 infection among the general pediatric population of the district was 27% (95% CI: 26.1–27.8). Adding this to the officially documented cases, the true overall prevalence was 32.8% (95% CI: 31.9–33.6) in contrast to the officially documented 8.0% (95% CI: 7.5–8.5) by June 2021. This translated into a proportion of 75.7% (95% CI: 74.4–77.0) of cases being officially undocumented, suggesting a high extent of silent SARS-CoV-2 infections in the pediatric population and possibly silent transmission. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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15 pages, 2485 KiB

Open AccessArticle

Cross-Reactive T Cell Response Exists in Chronic Lymphocytic Choriomeningitis Virus Infection upon Pichinde Virus Challenge

by Jasmin Mischke, Sebastian Klein, Austin Seamann, Immo Prinz, Liisa Selin, Dario Ghersi, Markus Cornberg and Anke R.M. Kraft

Viruses 2022, 14(10), 2293; https://doi.org/10.3390/v14102293 - 18 Oct 2022

Cited by 2 | Viewed by 2466

Abstract

Immunological memory to a previously encountered pathogen can influence the outcome of a sequential infection, which is called heterologous immunity. Lymphocytic choriomeningitis virus (LCMV) immune mice develop a NP205-specific T cell response that is cross-reactive to Pichinde virus infection (PICV). So far, limited [...] Read more.

Immunological memory to a previously encountered pathogen can influence the outcome of a sequential infection, which is called heterologous immunity. Lymphocytic choriomeningitis virus (LCMV) immune mice develop a NP205-specific T cell response that is cross-reactive to Pichinde virus infection (PICV). So far, limited data are available if cross-reactive T cell responses appear also during chronic infections with exhausted T cell responses. Exhaustion in chronic viral infections can be treated with checkpoint inhibitors, which might affect heterologous outcomes unexpectedly. The aim of this study was to investigate the cross-reactive immune response in chronic LCMV clone 13 (LCMVcl13) infection during primary PICV infection at phenotypic, functional, and T cell receptor (TCR) level. Moreover, the influence of checkpoint inhibitor therapy with αPD-L1 was investigated. Cross-reactive NP205-specific responses were present and functional in the chronic environment. Additionally, chronically infected mice were also protected from PICV mediated weight loss compared to naive PICV mice. An altered phenotype of NP205-specific T cells was detectable, but no major differences in the clonality and diversity of their TCR repertoire were observed. Checkpoint inhibitor treatment with αPD-L1 did alter chronic LCMV infection but had no major effect on heterologous immunity to PICV. Our study demonstrated that cross-reactive CD8⁺ T cells also exist in the setting of chronic infection, indicating a clinically relevant role of cross-reactive T cells in chronic infections. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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10 pages, 1491 KiB

Open AccessArticle

Healthcare-Associated COVID-19 across Five Pandemic Waves: Prediction Models and Genomic Analyses

by Thomas Demuyser, Lucie Seyler, Rhea Buttiens, Oriane Soetens, Els Van Nedervelde, Ben Caljon, Jessy Praet, Thomas Seyler, Joost Boeckmans, Jessy Meert, Robin Vanstokstraeten, Helena Martini, Florence Crombé, Denis Piérard, Sabine D. Allard and Ingrid Wybo

Viruses 2022, 14(10), 2292; https://doi.org/10.3390/v14102292 - 18 Oct 2022

Cited by 1 | Viewed by 1822

Abstract

Background: Healthcare-associated SARS-CoV-2 infections need to be explored further. Our study is an analysis of hospital-acquired infections (HAIs) and ambulatory healthcare workers (aHCWs) with SARS-CoV-2 across the pandemic in a Belgian university hospital. Methods: We compared HAIs with community-associated infections (CAIs) to identify [...] Read more.

Background: Healthcare-associated SARS-CoV-2 infections need to be explored further. Our study is an analysis of hospital-acquired infections (HAIs) and ambulatory healthcare workers (aHCWs) with SARS-CoV-2 across the pandemic in a Belgian university hospital. Methods: We compared HAIs with community-associated infections (CAIs) to identify the factors associated with having an HAI. We then performed a genomic cluster analysis of HAIs and aHCWs. We used this alongside the European Centre for Disease Control (ECDC) case source classifications of an HAI. Results: Between March 2020 and March 2022, 269 patients had an HAI. A lower BMI, a worse frailty index, lower C-reactive protein (CRP), and a higher thrombocyte count as well as death and length of stay were significantly associated with having an HAI. Using those variables to predict HAIs versus CAIs, we obtained a positive predictive value (PPV) of 83.6% and a negative predictive value (NPV) of 82.2%; the area under the ROC was 0.89. Genomic cluster analyses and representations on epicurves and minimal spanning trees delivered further insights into HAI dynamics across different pandemic waves. The genomic data were also compared with the clinical ECDC definitions for HAIs; we found that 90.0% of the ‘definite’, 87.8% of the ‘probable’, and 70.3% of the ‘indeterminate’ HAIs belonged to one of the twenty-two COVID-19 genomic clusters we identified. Conclusions: We propose a novel prediction model for HAIs. In addition, we show that the management of nosocomial outbreaks will benefit from genome sequencing analyses. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)

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16 pages, 2289 KiB

Open AccessArticle

Natural History of Marburg Virus Infection to Support Medical Countermeasure Development

by Jason E. Comer, Trevor Brasel, Shane Massey, David W. Beasley, Chris M. Cirimotich, Daniel C. Sanford, Ying-Liang Chou, Nancy A. Niemuth, Joseph Novak, Carol L. Sabourin, Michael Merchlinsky, James P. Long, Eric J. Stavale and Daniel N. Wolfe

Viruses 2022, 14(10), 2291; https://doi.org/10.3390/v14102291 - 18 Oct 2022

Cited by 9 | Viewed by 2596

Abstract

The Biomedical Advanced Research and Development Authority, part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, recognizes that the evaluation of medical countermeasures under the Animal Rule requires well-characterized and reproducible animal models that [...] Read more.

The Biomedical Advanced Research and Development Authority, part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, recognizes that the evaluation of medical countermeasures under the Animal Rule requires well-characterized and reproducible animal models that are likely to be predictive of clinical benefit. Marburg virus (MARV), one of two members of the genus Marburgvirus, is characterized by a hemorrhagic fever and a high case fatality rate for which there are no licensed vaccines or therapeutics available. This natural history study consisted of twelve cynomolgus macaques challenged with 1000 PFU of MARV Angola and observed for body weight, temperature, viremia, hematology, clinical chemistry, and coagulation at multiple time points. All animals succumbed to disease within 8 days and exhibited signs consistent with those observed in human cases, including viremia, fever, systemic inflammation, coagulopathy, and lymphocytolysis, among others. Additionally, this study determined the time from exposure to onset of disease manifestations and the time course, frequency, and magnitude of the manifestations. This study will be instrumental in the design and development of medical countermeasures to Marburg virus disease. Full article

(This article belongs to the Section Animal Viruses)

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7 pages, 839 KiB

Open AccessCommunication

Wild Red Deer (Cervus elaphus) Do Not Play a Role as Vectors or Reservoirs of SARS-CoV-2 in North-Eastern Poland

by Martyna Krupińska, Jakub Borkowski, Aleksander Goll, Joanna Nowicka, Karolina Baranowicz, Vincent Bourret, Tomas Strandin, Sanna Mäki, Ravi Kant, Tarja Sironen and Maciej Grzybek

Viruses 2022, 14(10), 2290; https://doi.org/10.3390/v14102290 - 18 Oct 2022

Cited by 7 | Viewed by 3615

Abstract

Several studies reported a high prevalence of SARS-CoV-2 among white-tailed deer in North America. Monitoring cervids in all regions to better understand SARS-CoV-2 infection and circulation in other deer populations has been urged. To evaluate deer exposure and/or infection to/by SARS-CoV-2 in Poland, [...] Read more.

Several studies reported a high prevalence of SARS-CoV-2 among white-tailed deer in North America. Monitoring cervids in all regions to better understand SARS-CoV-2 infection and circulation in other deer populations has been urged. To evaluate deer exposure and/or infection to/by SARS-CoV-2 in Poland, we sampled 90 red deer shot by hunters in five hunting districts in north-eastern Poland. Serum and nasopharyngeal swabs were collected, and then an immunofluorescent assay (IFA) to detect anti-SARS-CoV-2 antibodies was performed as well as real-time PCR with reverse transcription for direct virus detection. No positive samples were detected. There is no evidence of spillover of SARS-CoV-2 from the human to deer population in Poland. Full article

(This article belongs to the Special Issue Emerging Microbes, Infections and Spillovers)

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14 pages, 3990 KiB

Open AccessArticle

The Parapoynx stagnalis Nucleopolyhedrovirus (PastNPV), a Divergent Member of the Alphabaculovirus Group I Clade, Encodes a Homolog of Ran GTPase

by Robert L. Harrison and Daniel L. Rowley

Viruses 2022, 14(10), 2289; https://doi.org/10.3390/v14102289 - 18 Oct 2022

Cited by 1 | Viewed by 1988

Abstract

We report the analysis of the genome of a novel Alphabaculovirus, Parapoynx stagnalis nucleopolyhedrovirus isolate 473 (PastNPV-473), from cadavers of the rice case bearer, Parapoynx stagnalis Zeller (Lepidoptera: Crambidae), collected in rice fields in Kerala, India. High-throughput sequencing of DNA from PastNPV [...] Read more.

We report the analysis of the genome of a novel Alphabaculovirus, Parapoynx stagnalis nucleopolyhedrovirus isolate 473 (PastNPV-473), from cadavers of the rice case bearer, Parapoynx stagnalis Zeller (Lepidoptera: Crambidae), collected in rice fields in Kerala, India. High-throughput sequencing of DNA from PastNPV occlusion bodies and assembly of the data yielded a circular genome-length contig of 114,833 bp with 126 annotated opening reading frames (ORFs) and six homologous regions (hrs). Phylogenetic inference based on baculovirus core gene amino acid sequence alignments indicated that PastNPV is a member of the group I clade of viruses in genus Alphabaculovirus, but different phylogenetic methods yielded different results with respect to the placement of PastNPV and four similarly divergent alphabaculoviruses in the group I clade. Branch lengths and Kimura-2-parameter pairwise nucleotide distances indicated that PastNPV-473 cannot be classified in any of the currently listed species in genus Alphabaculovirus. A unique feature of the PastNPV genome was the presence of an ORF encoding a homolog of Ran GTPase, a regulator of nucleocytoplasmic trafficking. PastNPV appears to have acquired a homolog of Ran relatively recently from a lepidopteran host via horizontal gene transfer. Full article

(This article belongs to the Special Issue Entomopathogenic Viruses: Molecular, Cellular and Biotechnological Insights That Enhance Their Potential Application as Biopesticides)

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31 pages, 4414 KiB

Open AccessArticle

Host Cell Redox Alterations Promote Latent HIV-1 Reactivation through Atypical Transcription Factor Cooperativity

by Emily Cruz-Lorenzo, Nora-Guadalupe P. Ramirez, Jeon Lee, Sonali Pandhe, Lei Wang, Juan Hernandez-Doria, Adam M. Spivak, Vicente Planelles, Tianna Petersen, Mamta K. Jain, Elisabeth D. Martinez and Iván D’Orso

Viruses 2022, 14(10), 2288; https://doi.org/10.3390/v14102288 - 18 Oct 2022

Cited by 1 | Viewed by 2716

Abstract

Immune cell state alterations rewire HIV-1 gene expression, thereby influencing viral latency and reactivation, but the mechanisms are still unfolding. Here, using a screen approach on CD4⁺ T cell models of HIV-1 latency, we revealed Small Molecule Reactivators (SMOREs) with unique chemistries [...] Read more.

Immune cell state alterations rewire HIV-1 gene expression, thereby influencing viral latency and reactivation, but the mechanisms are still unfolding. Here, using a screen approach on CD4⁺ T cell models of HIV-1 latency, we revealed Small Molecule Reactivators (SMOREs) with unique chemistries altering the CD4⁺ T cell state and consequently promoting latent HIV-1 transcription and reactivation through an unprecedented mechanism of action. SMOREs triggered rapid oxidative stress and activated a redox-responsive program composed of cell-signaling kinases (MEK-ERK axis) and atypical transcription factor (AP-1 and HIF-1α) cooperativity. SMOREs induced an unusual AP-1 phosphorylation signature to promote AP-1/HIF-1α binding to the latent HIV-1 proviral genome for its activation. Consistently, latent HIV-1 reactivation was compromised with pharmacologic inhibition of oxidative stress sensing or of cell-signaling kinases, and transcription factor’s loss of expression, thus functionally linking the host redox-responsive program to viral transcriptional rewiring. Notably, SMOREs induced the redox program in primary CD4⁺ T cells and reactivated latent HIV-1 in aviremic patient samples alone and in combination with known latency-reversing agents, thus providing physiological relevance. Our findings suggest that manipulation of redox-sensitive pathways could be exploited to alter the course of HIV-1 latency, thus rendering host cells responsive to help achieve a sterilizing cure. Full article

(This article belongs to the Section Animal Viruses)

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20 pages, 3442 KiB

Open AccessArticle

Evaluation of Clinical Biomarkers Related to CD4 Recovery in HIV-Infected Patients—5-Year Observation

by Agnieszka Lembas, Andrzej Załęski, Tomasz Mikuła, Tomasz Dyda, Wojciech Stańczak and Alicja Wiercińska-Drapało

Viruses 2022, 14(10), 2287; https://doi.org/10.3390/v14102287 - 18 Oct 2022

Cited by 2 | Viewed by 2072

Abstract

Human Immunodeficiency Virus infection leads to the impairment of immune system function. Even long-term antiretroviral therapy uncommonly leads to the normalization of CD4 count and CD4:CD8 ratio. The aim of this study was to evaluate possible clinical biomarkers which may be related to [...] Read more.

Human Immunodeficiency Virus infection leads to the impairment of immune system function. Even long-term antiretroviral therapy uncommonly leads to the normalization of CD4 count and CD4:CD8 ratio. The aim of this study was to evaluate possible clinical biomarkers which may be related to CD4 and CD4:CD8 ratio recovery among HIV-infected patients with long-term antiretroviral therapy. The study included 68 HIV-infected patients undergoing sustained antiretroviral treatment for a minimum of 5 years. Clinical biomarkers such as age, gender, advancement of HIV infection, coinfections, comorbidities and applied ART regimens were analyzed in relation to the rates of CD4 and CD4:CD8 increase and normalization rates. The results showed that higher rates of CD4 normalization are associated with younger age (p = 0.034), higher CD4 count (p = 0.034) and starting the therapy during acute HIV infection (p = 0.012). Higher rates of CD4:CD8 ratio normalization are correlated with higher CD4 cell count (p = 0.022), high HIV viral load (p = 0.006) and acute HIV infection (p = 0.013). We did not observe statistically significant differences in CD4 recovery depending on gender, HCV/HBV coinfections, comorbidities and opportunistic infections. The obtained results advocate for current recommendations of introducing antiretroviral therapy as soon as possible, preferably during acute HIV infection, since it increases the chances of sufficient immune reconstruction. Full article

(This article belongs to the Special Issue HIV-1 Infection and Immunometabolism: Relevance to HIV Pathogenesis and Persistence 2.0)

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36 pages, 4315 KiB

Open AccessArticle

Comparative HIV-1 Phylogenies Characterized by PR/RT, Pol and Near-Full-Length Genome Sequences

by Cicek Topcu, Vasilis Georgiou, Johana Hezka Rodosthenous and Leondios G. Kostrikis

Viruses 2022, 14(10), 2286; https://doi.org/10.3390/v14102286 - 17 Oct 2022

Cited by 6 | Viewed by 2740

Abstract

In an effort to evaluate the accuracy of HIV-1 phylogenies based on genomes of increasing length, we developed a comprehensive near-full-length HIV-1 genome RT–PCR assay and performed a comparative evaluation via phylogenetic analyses. To this end, we conducted comparative analyses of HIV-1 phylogenies [...] Read more.

In an effort to evaluate the accuracy of HIV-1 phylogenies based on genomes of increasing length, we developed a comprehensive near-full-length HIV-1 genome RT–PCR assay and performed a comparative evaluation via phylogenetic analyses. To this end, we conducted comparative analyses of HIV-1 phylogenies derived based on HIV-1 PR/RT (2253–3359 in the HXB2 genome) and pol region (2253–5250 in the HXB2 genome) sequences isolated from 134 HIV-1-infected patients in Cyprus (2017–2019). The HIV-1 genotypic subtypes determined using six subtyping tools (REGA 3.0, COMET 2.3, jpHMM, SCUEAL, Stanford, and Geno2pheno) were compared to investigate the discrepancies generated among different tools. To evaluate the accuracy of defined HIV-1 phylogenies, the samples exhibiting at least one discrepant subtyping result among different subtyping tools in both PR/RT and pol regions or only in the pol region (n = 38) were selected for near-full-length HIV-1 genome (790–8795 in HXB2 genome) sequencing using a newly developed RT–PCR/sequencing assay. The obtained sequences were employed for HIV-1 genotypic subtype determination and subjected to comparative phylogenetic-based analyses. It was observed that 39.6% of the 134 samples presented discrepancies in the PR/RT region, while 28.4% presented discrepancies in the pol region. REGA 3.0 produced the fewest discrepancies collectively in both regions and was selected for subsequent subtyping and comparative phylogenetic analyses of near-full-length HIV-1 genome sequences. The analyses of near-full-length HIV-1 genome sequences identified 68.4% of the 38 ‘discrepant samples’ (n = 26) as belonging to uncharacterized recombinant HIV-1 strains, while 21.1% were circulating recombinant forms (CRFs) (n = 8) and 10.5% belonged to pure group M subtypes (n = 4). The findings demonstrated a significant reduction of 11.2% in discrepancies when pol region sequences were used compared to PR/RT region sequences, indicating that increased nucleotide sequence lengths are directly correlated with more consistent subtype classification. The results also revealed that if the discrepancy in pol region subtyping results persists, then there is a high likelihood (89.5%) that the query sequence is a recombinant HIV-1 strain, 68.4% of which belong to uncharacterized recombinant HIV-1 strains. The results of this study showed that REGA 3.0 presented the best performance in subtyping recombinant HIV-1 strains, while Stanford performed better in defining phylogenies of pure group M subtypes. The study highlights that, especially in populations with polyphyletic HIV-1 epidemics resulting in a high prevalence of recombinant HIV-1 strains, neither PR/RT nor pol region sequences are reliable for the determination of HIV-1 genotypic subtypes in samples showing discrepancies among different subtyping tools, and only near-full-length or full-length HIV-1 genome sequences are sufficiently accurate. Full article

(This article belongs to the Special Issue HIV Epidemiology and Drug Resistance)

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Open AccessArticle

Recombinant Human Cytomegalovirus Expressing an Analog-Sensitive Kinase pUL97 as Novel Tool for Functional Analyses

by Nadine Krämer, Martin Schütz, Uxía Gestal Mato, Lina Herhaus, Manfred Marschall and Christine Zimmermann

Viruses 2022, 14(10), 2285; https://doi.org/10.3390/v14102285 - 17 Oct 2022

Cited by 1 | Viewed by 2224

Abstract

The human cytomegalovirus (HCMV) is a member of the beta-herpesvirus family and inflicts life-long latent infections in its hosts. HCMV has been shown to manipulate and dysregulate many cellular processes. One major interactor with the cellular host is the viral kinase pUL97. The [...] Read more.

The human cytomegalovirus (HCMV) is a member of the beta-herpesvirus family and inflicts life-long latent infections in its hosts. HCMV has been shown to manipulate and dysregulate many cellular processes. One major interactor with the cellular host is the viral kinase pUL97. The UL97 gene is essential for viral replication, and kinase-deficient mutants of pUL97 display a severe replication defect. Recently, another group established an analog-sensitive version of the pUL97 protein. This mutant kinase can be treated with a non-hydrolysable ATP analog, thereby inhibiting its kinase function. This process is reversible by removing the ATP analog by media change. We introduced this mutant version of the pUL97 protein into the laboratory strain Ad169 of HCMV, BADwt, creating a BAD-UL97-as1 viral mutant. This mutant virus replicated normally in infected cells in the absence of the ATP analog and maintained its ability to phosphorylate its cellular substrates. However, when treated with the ATP analog, BAD-UL97-as1 displayed a defect in the production of intra- and extracellular viral DNA and in the production of viral progeny. Furthermore, in the presence of 3MB-PP1, a well-established substrate of pUL97 was no longer hyperphosphorylated. This effect was detectable as early as 4 h post treatment, which allows for studies on pUL97 without the complication of low viral titers. Nevertheless, we observed off-target effects of 3MB-PP1 on several cellular processes, which should be considered with this approach. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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Viruses, Volume 14, Issue 10 (October 2022) – 233 articles

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