Viruses

17 pages, 1050 KiB

Open AccessArticle

Association of Increased Programmed Death Ligand 1 Expression and Regulatory T Cells Infiltration with Higher Hepatocellular Carcinoma Recurrence in Patients with Hepatitis B Virus Pre-S2 Mutant after Curative Surgical Resection

by Long-Bin Jeng, Tsai-Chung Li, Shih-Chao Hsu and Chiao-Fang Teng

Viruses 2022, 14(6), 1346; https://doi.org/10.3390/v14061346 - 20 Jun 2022

Cited by 2 | Viewed by 2653

Abstract

Although surgical resection is available as a potentially curative therapy for hepatocellular carcinoma (HCC), high recurrence of HCC after surgery remains a serious obstacle for long-term patient survival. Therefore, the discovery of valuable prognostic biomarkers for HCC recurrence is urgently needed. Pre-S2 mutant [...] Read more.

Although surgical resection is available as a potentially curative therapy for hepatocellular carcinoma (HCC), high recurrence of HCC after surgery remains a serious obstacle for long-term patient survival. Therefore, the discovery of valuable prognostic biomarkers for HCC recurrence is urgently needed. Pre-S2 mutant is a mutant form of hepatitis B virus (HBV) large surface protein which is expressed from the HBV surface gene harboring deletion mutations spanning the pre-S2 gene segment. Pre-S2 mutant-positive HCC patients have been regarded as a high-risk population of HCC recurrence after resection surgery and display increased immune checkpoint programmed death ligand 1 (PD-L1) expression and pro-tumor regulatory T cells (Tregs) infiltration in tumor tissues. In this study, the association of higher levels of PD-L1 expression and Tregs infiltration in tumor tissues with post-operative HCC recurrence in pre-S2 mutant-positive HCC patients was evaluated. We found that patients with pre-S2 mutant in combination with higher levels of PD-L1 expression and Tregs infiltration in tumor tissues were independently associated with a higher risk of HCC recurrence (hazard ratio, 4.109; p value = 0.0011) and poorer recurrence-free survival (median, 8.2 versus 18.0 months; p value = 0.0004) than those of patients with either one or two of these three biomarkers. Furthermore, a combination of pre-S2 mutant, intra-tumoral PD-L1 expression, and tumor-infiltrating Tregs exhibited superior performance in identifying patients at a higher risk of HCC recurrence (area under the receiver operating characteristic curve, 0.8400). Collectively, this study suggests that higher levels of PD-L1 expression and Tregs infiltration in tumor tissues predicted a higher risk of HCC recurrence in pre-S2 mutant-positive HCC patients after curative surgical resection. Full article

(This article belongs to the Special Issue New Frontiers in Small DNA Virus Research)

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13 pages, 1021 KiB

Open AccessReview

Repurposing Molnupiravir for COVID-19: The Mechanisms of Antiviral Activity

by Ashley Jia Wen Yip, Zheng Yao Low, Vincent T. K. Chow and Sunil K. Lal

Viruses 2022, 14(6), 1345; https://doi.org/10.3390/v14061345 - 20 Jun 2022

Cited by 29 | Viewed by 4046

Abstract

Molnupiravir is a β-d-N4-hydroxycytidine-5′-isopropyl ester (NHC) compound that exerts antiviral activity against various RNA viruses such as influenza, SARS, and Ebola viruses. Thus, the repurposing of Molnupiravir has gained significant attention for combatting infection with SARS-CoV-2, the etiological agent of COVID-19. Recently, Molnupiravir [...] Read more.

Molnupiravir is a β-d-N4-hydroxycytidine-5′-isopropyl ester (NHC) compound that exerts antiviral activity against various RNA viruses such as influenza, SARS, and Ebola viruses. Thus, the repurposing of Molnupiravir has gained significant attention for combatting infection with SARS-CoV-2, the etiological agent of COVID-19. Recently, Molnupiravir was granted authorization for the treatment of mild-to-moderate COVID-19 in adults. Findings from in vitro experiments, in vivo studies and clinical trials reveal that Molnupiravir is effective against SARS-CoV-2 by inducing viral RNA mutagenesis, thereby giving rise to mutated complementary RNA strands that generate non-functional viruses. To date, the data collectively suggest that Molnupiravir possesses promising antiviral activity as well as favorable prophylactic efficacy, attributed to its effective mutagenic property of disrupting viral replication. This review discusses the mechanisms of action of Molnupiravir and highlights its clinical utility by disabling SARS-CoV-2 replication, thereby ameliorating COVID-19 severity. Despite relatively few short-term adverse effects thus far, further detailed clinical studies and long-term pharmacovigilance are needed in view of its mutagenic effects. Full article

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

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15 pages, 2496 KiB

Open AccessArticle

The Viral Susceptibility of the Haloferax Species

by Zaloa Aguirre Sourrouille, Sabine Schwarzer, Sebastian Lequime, Hanna M. Oksanen and Tessa E. F. Quax

Viruses 2022, 14(6), 1344; https://doi.org/10.3390/v14061344 - 20 Jun 2022

Cited by 5 | Viewed by 3249

Abstract

Viruses can infect members of all three domains of life. However, little is known about viruses infecting archaea and the mechanisms that determine their host interactions are poorly understood. Investigations of molecular mechanisms of viral infection rely on genetically accessible virus–host model systems. [...] Read more.

Viruses can infect members of all three domains of life. However, little is known about viruses infecting archaea and the mechanisms that determine their host interactions are poorly understood. Investigations of molecular mechanisms of viral infection rely on genetically accessible virus–host model systems. Euryarchaea belonging to the genus Haloferax are interesting models, as a reliable genetic system and versatile microscopy methods are available. However, only one virus infecting the Haloferax species is currently available. In this study, we tested ~100 haloarchaeal virus isolates for their infectivity on 14 Haloferax strains. From this, we identified 10 virus isolates in total capable of infecting Haloferax strains, which represented myovirus or siphovirus morphotypes. Surprisingly, the only susceptible strain of all 14 tested was Haloferax gibbonsii LR2-5, which serves as an auspicious host for all of these 10 viruses. By applying comparative genomics, we shed light on factors determining the host range of haloarchaeal viruses on Haloferax. We anticipate our study to be a starting point in the study of haloarchaeal virus–host interactions. Full article

(This article belongs to the Special Issue Archaeal Virology)

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15 pages, 2426 KiB

Open AccessArticle

Development of a Monoclonal Antibody to Pig CD69 Reveals Early Activation of T Cells in Pig after PRRSV and ASFV Infection

by Yunfei Tian, Yuxin Hao, Maoli Dong, Shuai Li, Dongyue Wang, Fei Jiang, Qingqing Wang, Xiaoli Hao, Yi Yang, Nanhua Chen, Jianzhong Zhu, Junqing Guo, Jiajun Wu, Shaobin Shang and Jiyong Zhou

Viruses 2022, 14(6), 1343; https://doi.org/10.3390/v14061343 - 20 Jun 2022

Cited by 6 | Viewed by 2939

Abstract

The CD69 molecule, as an early activation marker of lymphocytes, is often used to assess the activation of cellular immunity. However, for pigs, an anti-pig CD69 antibody is not yet available for this purpose after infection or vaccination. In this study, a monoclonal [...] Read more.

The CD69 molecule, as an early activation marker of lymphocytes, is often used to assess the activation of cellular immunity. However, for pigs, an anti-pig CD69 antibody is not yet available for this purpose after infection or vaccination. In this study, a monoclonal antibody (mAb) against pig CD69 was produced by peptide immunization and hybridoma technique. One mAb (5F12) showed good reactivity with pig CD69 that was expressed in transfected-HEK-293T cells and on mitogen-activated porcine peripheral blood mononuclear cells (PBMCs) by indirect immunofluorescence assay and flow cytometry. This mAb did not cross-react with activated lymphocytes from mouse, bovine, and chicken. Epitope mapping showed that the epitope recognized by this mAb was located at amino acid residues 147–161 of pig CD69. By conjugating with fluorochrome, this mAb was used to detect the early activation of lymphocytes in PRRSV- and ASFV-infected pigs by flow cytometry. The results showed that PRRSV infection induced the dominant activation of CD4 T cells in mediastinal lymph nodes and CD8 T cells in the spleen at 14 days post-infection, in terms of CD69 expression. In an experiment on ASFV infection, we found that ASFV infection resulted in the early activation of NK cells, B cells, and distinct T cell subsets with variable magnitude in PBMCs, spleen, and submandibular lymph nodes. Our study revealed an early event of lymphocyte and T cell activation after PRRSV and ASFV infections and provides an important immunological tool for the in-depth analysis of cellular immune response in pigs after infection or vaccination. Full article

(This article belongs to the Topic Veterinary Infectious Diseases)

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14 pages, 1485 KiB

Open AccessArticle

Nucleic Acid Preservation Card Surveillance Is Effective for Monitoring Arbovirus Transmission on Crocodile Farms and Provides a One Health Benefit to Northern Australia

by Nina Kurucz, Jamie Lee McMahon, Allan Warchot, Glen Hewitson, Jean Barcelon, Frederick Moore, Jasmin Moran, Jessica J. Harrison, Agathe M. G. Colmant, Kyran M. Staunton, Scott A. Ritchie, Michael Townsend, Dagmar Meyer Steiger, Roy A. Hall, Sally R. Isberg and Sonja Hall-Mendelin

Viruses 2022, 14(6), 1342; https://doi.org/10.3390/v14061342 - 20 Jun 2022

Cited by 4 | Viewed by 2082

Abstract

The Kunjin strain of West Nile virus (WNV_KUN) is a mosquito-transmitted flavivirus that can infect farmed saltwater crocodiles in Australia and cause skin lesions that devalue the hides of harvested animals. We implemented a surveillance system using honey-baited nucleic acid preservation [...] Read more.

The Kunjin strain of West Nile virus (WNV_KUN) is a mosquito-transmitted flavivirus that can infect farmed saltwater crocodiles in Australia and cause skin lesions that devalue the hides of harvested animals. We implemented a surveillance system using honey-baited nucleic acid preservation cards to monitor WNV_KUN and another endemic flavivirus pathogen, Murray Valley encephalitis virus (MVEV), on crocodile farms in northern Australia. The traps were set between February 2018 and July 2020 on three crocodile farms in Darwin (Northern Territory) and one in Cairns (North Queensland) at fortnightly intervals with reduced trapping during the winter months. WNV_KUN RNA was detected on all three crocodile farms near Darwin, predominantly between March and May of each year. Two of the NT crocodile farms also yielded the detection of MVE viral RNA sporadically spread between April and November in 2018 and 2020. In contrast, no viral RNA was detected on crocodile farms in Cairns during the entire trapping period. The detection of WNV_KUN and MVEV transmission by FTA^TM cards on farms in the Northern Territory generally correlated with the detection of their transmission to sentinel chicken flocks in nearby localities around Darwin as part of a separate public health surveillance program. While no isolates of WNV_KUN or MVEV were obtained from mosquitoes collected on Darwin crocodile farms immediately following the FTA^TM card detections, we did isolate another flavivirus, Kokobera virus (KOKV), from Culex annulirostris mosquitoes. Our studies support the use of the FTA^TM card system as a sensitive and accurate method to monitor the transmission of WNV_KUN and other arboviruses on crocodile farms to enable the timely implementation of mosquito control measures. Our detection of MVEV transmission and isolation of KOKV from mosquitoes also warrants further investigation of their potential role in causing diseases in crocodiles and highlights a “One Health” issue concerning arbovirus transmission to crocodile farm workers. In this context, the introduction of FTA^TM cards onto crocodile farms appears to provide an additional surveillance tool to detect arbovirus transmission in the Darwin region, allowing for a more timely intervention of vector control by relevant authorities. Full article

(This article belongs to the Section Invertebrate Viruses)

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16 pages, 3042 KiB

Open AccessArticle

The Potyviral Protein 6K1 Reduces Plant Proteases Activity during Turnip mosaic virus Infection

by Sayanta Bera, Gabriella D. Arena, Swayamjit Ray, Sydney Flannigan and Clare L. Casteel

Viruses 2022, 14(6), 1341; https://doi.org/10.3390/v14061341 - 20 Jun 2022

Cited by 13 | Viewed by 3194

Abstract

Potyviral genomes encode just 11 major proteins and multifunctionality is associated with most of these proteins at different stages of the virus infection cycle. Some potyviral proteins modulate phytohormones and protein degradation pathways and have either pro- or anti-viral/insect vector functions. Our previous [...] Read more.

Potyviral genomes encode just 11 major proteins and multifunctionality is associated with most of these proteins at different stages of the virus infection cycle. Some potyviral proteins modulate phytohormones and protein degradation pathways and have either pro- or anti-viral/insect vector functions. Our previous work demonstrated that the potyviral protein 6K1 has an antagonistic effect on vectors when expressed transiently in host plants, suggesting plant defenses are regulated. However, to our knowledge the mechanisms of how 6K1 alters plant defenses and how 6K1 functions are regulated are still limited. Here we show that the 6K1 from Turnip mosaic virus (TuMV) reduces the abundance of transcripts related to jasmonic acid biosynthesis and cysteine protease inhibitors when expressed in Nicotiana benthamiana relative to controls. 6K1 stability increased when cysteine protease activity was inhibited chemically, showing a mechanism to the rapid turnover of 6K1 when expressed in trans. Using RNAseq, qRT-PCR, and enzymatic assays, we demonstrate TuMV reprograms plant protein degradation pathways on the transcriptional level and increases 6K1 stability at later stages in the infection process. Moreover, we show 6K1 decreases plant protease activity in infected plants and increases TuMV accumulation in systemic leaves compared to controls. These results suggest 6K1 has a pro-viral function in addition to the anti-insect vector function we observed previously. Although the host targets of 6K1 and the impacts of 6K1-induced changes in protease activity on insect vectors are still unknown, this study enhances our understanding of the complex interactions occurring between plants, potyviruses, and vectors. Full article

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

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11 pages, 2439 KiB

Open AccessArticle

Novel Bacteriophage Specific against Staphylococcus epidermidis and with Antibiofilm Activity

by Rima Fanaei Pirlar, Jeroen Wagemans, Luis Ponce Benavente, Rob Lavigne, Andrej Trampuz and Mercedes Gonzalez Moreno

Viruses 2022, 14(6), 1340; https://doi.org/10.3390/v14061340 - 20 Jun 2022

Cited by 14 | Viewed by 3224

Abstract

Staphylococcus epidermidis has emerged as the most important pathogen in infections related to indwelling medical devices, and although these infections are not life-threatening, their frequency and the fact that they are extremely difficult to treat represent a serious burden on the public health [...] Read more.

Staphylococcus epidermidis has emerged as the most important pathogen in infections related to indwelling medical devices, and although these infections are not life-threatening, their frequency and the fact that they are extremely difficult to treat represent a serious burden on the public health system. Treatment is complicated by specific antibiotic resistance genes and the formation of biofilms. Hence, novel therapeutic strategies are needed to fight these infections. A novel bacteriophage CUB-EPI_14 specific to the bacterial species S. epidermidis was isolated from sewage and characterized genomically and phenotypically. Its genome contains a total of 46,098 bp and 63 predicted genes, among which some have been associated with packaging and lysis-associated proteins, structural proteins, or DNA- and metabolism-associated proteins. No lysogeny-associated proteins or known virulence proteins were identified in the phage genome. CUB-EPI_14 showed stability over a wide range of temperatures (from −20 °C to 50 °C) and pH values (pH 3–pH 12) and a narrow host range against S. epidermidis. Potent antimicrobial and antibiofilm activities were observed when the phage was tested against a highly susceptible bacterial isolate. These encouraging results open the door to new therapeutic opportunities in the fight against resilient biofilm-associated infections caused by S. epidermidis. Full article

(This article belongs to the Section Bacterial Viruses)

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8 pages, 257 KiB

Open AccessArticle

Weight of Clinical and Social Determinants of Metabolic Syndrome in People Living with HIV

by Maria Mazzitelli, Paolo Fusco, Michele Brogna, Alfredo Vallone, Laura D’Argenio, Giuseppina Beradelli, Giuseppe Foti, Carmelo Mangano, Maria Stella Carpentieri, Lucio Cosco, Paolo Scerbo, Armando Priamo, Nicola Serrao, Antonio Mastroianni, Chiara Costa, Maria Teresa Tassone, Vincenzo Scaglione, Francesca Serapide, Enrico Maria Trecarichi and Carlo Torti

Viruses 2022, 14(6), 1339; https://doi.org/10.3390/v14061339 - 20 Jun 2022

Cited by 10 | Viewed by 2165

Abstract

Background. Comorbidities in people living with HIV (PLWH) represent a major clinical challenge today, and metabolic syndrome (MTBS) is one of the most important. Objective. Our objective was to assess the prevalence of MTBS and the role of both clinical/socio-behavioral risk factors for [...] Read more.

Background. Comorbidities in people living with HIV (PLWH) represent a major clinical challenge today, and metabolic syndrome (MTBS) is one of the most important. Objective. Our objective was to assess the prevalence of MTBS and the role of both clinical/socio-behavioral risk factors for MTBS in a cohort of PLWH. Methods. All PLWH, over 18 years of age, attending all Infectious Disease Units in Calabria Region (Southern Italy) for their routine checks from October 2019–January 2020 were enrolled. MTBS was defined by NCEP-ATP III criteria. Logistic regression analysis was performed to assess factors significantly associated with the main outcome (MTBS). Results. We enrolled 356 PLWH, mostly males (68.5%), with a mean age of 49 years (standard deviation: 12), including 98 subjects with and 258 without MTBS. At logistic regression analysis, a statistically significant association was found between MTBS and alcohol use, osteoporosis, polypharmacy, and a history of AIDS. Conclusions. Identifying and addressing risk factors, including those that are socio-behavioral or lifestyle-related, is crucial to prevent and treat MTBS. Our results suggest the importance of implementing educational/multidimensional interventions to prevent MTBS in PLWH, especially for those with particular risk factors (alcohol abuse, osteoporosis, previous AIDS events, and polypharmacy). Moreover, alcohol consumption or abuse should be routinely investigated in clinical practice. Full article

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

16 pages, 1003 KiB

Open AccessReview

Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection

by William Rodriguez and Mandy Muller

Viruses 2022, 14(6), 1338; https://doi.org/10.3390/v14061338 - 20 Jun 2022

Cited by 13 | Viewed by 3505

Abstract

Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity [...] Read more.

Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity of mechanisms that differ from one virus to the next. These inhibitory strategies include the negative regulation of viral RNA stability, translation, and even the manipulation of RNA granule formation during viral infection. Even more surprisingly, SHFL is the first human protein found to directly inhibit the activity of the -1 programmed ribosomal frameshift, a translation recoding strategy utilized across nearly all domains of life and several human viruses. Recent literature has shown that SHFL expression also significantly impacts viral pathogenesis in mouse models, highlighting its in vivo efficacy. To help reconcile the many mechanisms by which SHFL restricts viral replication, we provide here a comprehensive review of this complex ISG, its influence over viral RNA fate, and the implications of its functions on the virus-host arms race for control of the cell. Full article

(This article belongs to the Special Issue Signaling Pathways in Viral Infection and Antiviral Immunity)

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17 pages, 1228 KiB

Open AccessReview

Extracellular Polymeric Substances: Still Promising Antivirals

by Raquel Bello-Morales, Sabina Andreu, Vicente Ruiz-Carpio, Inés Ripa and José Antonio López-Guerrero

Viruses 2022, 14(6), 1337; https://doi.org/10.3390/v14061337 - 19 Jun 2022

Cited by 13 | Viewed by 3352

Abstract

Sulfated polysaccharides and other polyanions have been promising candidates in antiviral research for decades. These substances gained attention as antivirals when they demonstrated a high inhibitory effect in vitro against human immunodeficiency virus (HIV) and other enveloped viruses. However, that initial interest was [...] Read more.

Sulfated polysaccharides and other polyanions have been promising candidates in antiviral research for decades. These substances gained attention as antivirals when they demonstrated a high inhibitory effect in vitro against human immunodeficiency virus (HIV) and other enveloped viruses. However, that initial interest was followed by wide skepticism when in vivo assays refuted the initial results. In this paper we review the use of sulfated polysaccharides, and other polyanions, in antiviral therapy, focusing on extracellular polymeric substances (EPSs). We maintain that, in spite of those early difficulties, the use of polyanions and, specifically, the use of EPSs, in antiviral therapy should be reconsidered. We base our claim in several points. First, early studies showed that the main disadvantage of sulfated polysaccharides and polyanions is their low bioavailability, but this difficulty can be overcome by the use of adequate administration strategies, such as nebulization of aerosols to gain access to respiratory airways. Second, several sulfated polysaccharides and EPSs have demonstrated to be non-toxic in animals. Finally, these macromolecules are non-specific and therefore they might be used against different variants or even different viruses. Full article

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

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24 pages, 1250 KiB

Open AccessReview

Detection of Ancient Viruses and Long-Term Viral Evolution

by Luca Nishimura, Naoko Fujito, Ryota Sugimoto and Ituro Inoue

Viruses 2022, 14(6), 1336; https://doi.org/10.3390/v14061336 - 18 Jun 2022

Cited by 9 | Viewed by 6278

Abstract

The COVID-19 outbreak has reminded us of the importance of viral evolutionary studies as regards comprehending complex viral evolution and preventing future pandemics. A unique approach to understanding viral evolution is the use of ancient viral genomes. Ancient viruses are detectable in various [...] Read more.

The COVID-19 outbreak has reminded us of the importance of viral evolutionary studies as regards comprehending complex viral evolution and preventing future pandemics. A unique approach to understanding viral evolution is the use of ancient viral genomes. Ancient viruses are detectable in various archaeological remains, including ancient people’s skeletons and mummified tissues. Those specimens have preserved ancient viral DNA and RNA, which have been vigorously analyzed in the last few decades thanks to the development of sequencing technologies. Reconstructed ancient pathogenic viral genomes have been utilized to estimate the past pandemics of pathogenic viruses within the ancient human population and long-term evolutionary events. Recent studies revealed the existence of non-pathogenic viral genomes in ancient people’s bodies. These ancient non-pathogenic viruses might be informative for inferring their relationships with ancient people’s diets and lifestyles. Here, we reviewed the past and ongoing studies on ancient pathogenic and non-pathogenic viruses and the usage of ancient viral genomes to understand their long-term viral evolution. Full article

(This article belongs to the Special Issue Virus Bioinformatics 2022)

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15 pages, 1170 KiB

Open AccessReview

Exploring the Mumps Virus Glycoproteins: A Review

by Jasmine Rae Frost, Saba Shaikh and Alberto Severini

Viruses 2022, 14(6), 1335; https://doi.org/10.3390/v14061335 - 18 Jun 2022

Cited by 6 | Viewed by 2750

Abstract

The resurgence of mumps in vaccinated adult populations has raised concerns about possible waning vaccine immunity or a potential lack of protection to the circulating strain. A number of individual studies have investigated if there are amino acid variations between the circulating wild-type [...] Read more.

The resurgence of mumps in vaccinated adult populations has raised concerns about possible waning vaccine immunity or a potential lack of protection to the circulating strain. A number of individual studies have investigated if there are amino acid variations between the circulating wild-type strains and vaccine strains. In these studies, the HN and F mumps surface glycoproteins have been of interest, because of their role in viral infection, and because the HN protein is the target of neutralizing antibodies. Here, we summarize the single nucleotide variants and their potential effect that have been identified between mumps genotypes in the HN and F proteins. Full article

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

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10 pages, 2907 KiB

Open AccessArticle

Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies

by Hao Zhou, Belinda M. Dcosta, Nathaniel R. Landau and Takuya Tada

Viruses 2022, 14(6), 1334; https://doi.org/10.3390/v14061334 - 18 Jun 2022

Cited by 57 | Viewed by 4297

Abstract

The recent emergence of the Omicron BA.1 and BA.2 variants with heavily mutated spike proteins has posed a challenge to the effectiveness of current vaccines and to monoclonal antibody therapy for severe COVID-19. After two immunizations of individuals with no history of previous [...] Read more.

The recent emergence of the Omicron BA.1 and BA.2 variants with heavily mutated spike proteins has posed a challenge to the effectiveness of current vaccines and to monoclonal antibody therapy for severe COVID-19. After two immunizations of individuals with no history of previous SARS-CoV-2 infection with BNT162b2 vaccine, neutralizing titer against BA.1 and BA.2 were 20-fold decreased compared to titers against the parental D614G virus. A third immunization boosted overall neutralizing titers by about 5-fold but titers against BA.1 and BA.2 remained about 10-fold below that of D614G. Both Omicron variants were highly resistant to several of the emergency use authorized therapeutic monoclonal antibodies. The variants were highly resistant to Regeneron REGN10933 and REGN10987 and Lilly LY-CoV555 and LY-CoV016 while Vir-7831 and the mixture of AstraZeneca monoclonal antibodies AZD8895 and AZD1061 were significantly decreased in neutralizing titer. Strikingly, a single monoclonal antibody LY-CoV1404 potently neutralized both Omicron variants. Full article

(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)

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17 pages, 6084 KiB

Open AccessArticle

Nuances of Responses to Two Sources of Grapevine Leafroll Disease on Pinot Noir Grown in the Field for 17 Years

by Jean-Sébastien Reynard, Justine Brodard, Vivian Zufferey, Markus Rienth, Paul Gugerli, Olivier Schumpp and Arnaud G. Blouin

Viruses 2022, 14(6), 1333; https://doi.org/10.3390/v14061333 - 18 Jun 2022

Cited by 4 | Viewed by 2691

Abstract

Grapevine leafroll disease (GLD) is one of the most economically damaging virus diseases in grapevine, with grapevine leafroll-associated virus 1 (GLRaV-1) and grapevine leafroll-associated virus 3 (GLRaV-3) as the main contributors. This study complements a previously published transcriptomic analysis and compared the impact [...] Read more.

Grapevine leafroll disease (GLD) is one of the most economically damaging virus diseases in grapevine, with grapevine leafroll-associated virus 1 (GLRaV-1) and grapevine leafroll-associated virus 3 (GLRaV-3) as the main contributors. This study complements a previously published transcriptomic analysis and compared the impact of two different forms of GLD to a symptomless control treatment: a mildly symptomatic form infected with GLRaV-1 and a severe form with exceptionally early leafroll symptoms (up to six weeks before veraison) infected with GLRaV-1 and GLRaV-3. Vine physiology and fruit composition in 17-year-old Pinot noir vines were measured and a gradient of vigor, yield, and berry quality (sugar content and berry weight) was observed between treatments. Virome composition, confirmed by individual RT-PCR, was compared with biological indexing. Three divergent viromes were recovered, containing between four to seven viruses and two viroids. They included the first detection of grapevine asteroid mosaic-associated virus in Switzerland. This virus did not cause obvious symptoms on the indicators used in biological indexing. Moreover, the presence of grapevine virus B (GVB) did not cause the expected corky bark symptoms on the indicators, thus underlining the important limitations of the biological indexing. Transmission of GLRaV-3 alone or in combination with GVB by Planococcus comstocki mealybug did not reproduce the strong symptoms observed on the donor plant infected with a severe form of GLD. This result raises questions about the contribution of each virus to the symptomatology of the plant. Full article

(This article belongs to the Special Issue Closteroviridae)

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10 pages, 1688 KiB

Open AccessArticle

Developing Pseudovirus-Based Neutralization Assay against Omicron-Included SARS-CoV-2 Variants

by Hancong Sun, Jinghan Xu, Guanying Zhang, Jin Han, Meng Hao, Zhengshan Chen, Ting Fang, Xiangyang Chi and Changming Yu

Viruses 2022, 14(6), 1332; https://doi.org/10.3390/v14061332 - 18 Jun 2022

Cited by 16 | Viewed by 4213

Abstract

The global spread of SARS-CoV-2 and its variants poses a serious threat to human health worldwide. Recently, the emergence of Omicron has presented a new challenge to the prevention and control of the COVID-19 pandemic. A convenient and reliable in vitro neutralization assay [...] Read more.

The global spread of SARS-CoV-2 and its variants poses a serious threat to human health worldwide. Recently, the emergence of Omicron has presented a new challenge to the prevention and control of the COVID-19 pandemic. A convenient and reliable in vitro neutralization assay is an important method for validating the efficiency of antibodies, vaccines, and other potential drugs. Here, we established an effective assay based on a pseudovirus carrying a full-length spike (S) protein of SARS-CoV-2 variants in the HIV-1 backbone, with a luciferase reporter gene inserted into the non-replicate pseudovirus genome. The key parameters for packaging the pseudovirus were optimized, including the ratio of the S protein expression plasmids to the HIV backbone plasmids and the collection time for the Alpha, Beta, Gamma, Kappa, and Omicron pseudovirus particles. The pseudovirus neutralization assay was validated using several approved or developed monoclonal antibodies, underscoring that Omicron can escape some neutralizing antibodies, such as REGN10987 and REGN10933, while S309 and ADG-2 still function with reduced neutralization capability. The neutralizing capacity of convalescent plasma from COVID-19 convalescent patients in Wuhan was tested against these pseudoviruses, revealing the immune evasion of Omicron. Our work established a practical pseudovirus-based neutralization assay for SARS-CoV-2 variants, which can be conducted safely under biosafety level-2 (BSL-2) conditions, and this assay will be a promising tool for studying and characterizing vaccines and therapeutic candidates against Omicron-included SARS-CoV-2 variants. 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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15 pages, 2111 KiB

Open AccessArticle

Evaluation of New Polyclonal Antibody Developed for Serological Diagnostics of Tomato Mosaic Virus

by Michaela Mrkvová, Richard Hančinský, Simona Grešíková, Šarlota Kaňuková, Ján Barilla, Miroslav Glasa, Pavol Hauptvogel, Ján Kraic and Daniel Mihálik

Viruses 2022, 14(6), 1331; https://doi.org/10.3390/v14061331 - 18 Jun 2022

Cited by 13 | Viewed by 2913

Abstract

Plant viruses threaten agricultural production by reducing the yield, quality, and economical benefits. Tomato mosaic virus (ToMV) from the genus Tobamovirus causes serious losses in the quantity and quality of tomato production. The management of plant protection is very difficult, mainly due to [...] Read more.

Plant viruses threaten agricultural production by reducing the yield, quality, and economical benefits. Tomato mosaic virus (ToMV) from the genus Tobamovirus causes serious losses in the quantity and quality of tomato production. The management of plant protection is very difficult, mainly due to the vector-less transmission of ToMV. Resistant breeding generally has low effectiveness. The most practical approach is the use of a rapid diagnostic assay of the virus’ presence before the symptoms occur in plants, followed by the eradication of virus-infected plants. Such approaches also include serological detection methods (ELISA and Western immunoblotting), where antibodies need to be developed for an immunochemical reaction. The development and characterization of polyclonal antibodies for the detection of ToMV with appropriate parameters (sensitivity, specificity, and cross-reactivity) were the subjects of this study. A new polyclonal antibody, AB-1, was developed in immunized rabbits using the modified oligopeptides with antigenic potential (sequences are revealed) derived from the coat protein of ToMV SL-1. the developed polyclonal antibody. AB-1, showed higher sensitivity when compared with commercially available analogs. It also detected ToMV in infected pepper and eggplant plants, and detected another two tobamoviruses (TMV and PMMoV) and ToMV in soil rhizosphere samples and root residues, even two years after the cultivation of the infected tomato plant. Full article

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

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13 pages, 6507 KiB

Open AccessArticle

SARS-CoV-2, Placental Histopathology, Gravity of Infection and Immunopathology: Is There an Association?

by Leonardo Resta, Antonella Vimercati, Gerardo Cazzato, Margherita Fanelli, Sara Vincenza Scarcella, Giuseppe Ingravallo, Anna Colagrande, Sara Sablone, Mary Stolfa, Francesca Arezzo, Teresa Lettini and Roberta Rossi

Viruses 2022, 14(6), 1330; https://doi.org/10.3390/v14061330 - 18 Jun 2022

Cited by 14 | Viewed by 2553

Abstract

(1) Background: As the pandemic months progress, more and more evidence shows that the placenta acts as a “barrier” to SARS-CoV-2, although rare cases of vertical transmission have been described. (2) Methods: In an attempt to investigate whether the symptoms’ severity was related [...] Read more.

(1) Background: As the pandemic months progress, more and more evidence shows that the placenta acts as a “barrier” to SARS-CoV-2, although rare cases of vertical transmission have been described. (2) Methods: In an attempt to investigate whether the symptoms’ severity was related to different placental histological characteristics and the immune microenvironment, we subdivided 29 placentas from 29 mothers positive for SARS-CoV-2 into two groups, depending on the symptomatology (moderate/severe vs. asymptomatic/mild), performing immunohistochemical investigations for CD4 + and CD8 + T lymphocytes, as well as for CD68 + macrophage. We also evaluated the immuno-expression of the ACE2 receptor at the placental level. These two groups were compared to a control group of 28 placentas from 28 SARS-CoV-2-negative healthy mothers. (3) Results: The symptoms (likely to be related to viremia) were statistically significantly correlated (p < 0.05) with histopathological changes, such as maternal malperfusion, decidual arteriopathy, blood vessel thrombus of fetal relevance. Furthermore, the immuno-expression of ACE2 was significantly lower in SARS-CoV-2-positive groups vs. control group (p = 0.001). (4) Conclusions: There is still much to study and discover regarding the relationship between SARS-CoV-2 and histological changes in placentas and how the latter might contribute to various neonatal clinical outcomes, such as prematurity. Full article

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

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13 pages, 1816 KiB

Open AccessArticle

Identification of Phage Receptor-Binding Protein Sequences with Hidden Markov Models and an Extreme Gradient Boosting Classifier

by Dimitri Boeckaerts, Michiel Stock, Bernard De Baets and Yves Briers

Viruses 2022, 14(6), 1329; https://doi.org/10.3390/v14061329 - 17 Jun 2022

Cited by 14 | Viewed by 5094

Abstract

Receptor-binding proteins (RBPs) of bacteriophages initiate the infection of their corresponding bacterial host and act as the primary determinant for host specificity. The ever-increasing amount of sequence data enables the development of predictive models for the automated identification of RBP sequences. However, the [...] Read more.

Receptor-binding proteins (RBPs) of bacteriophages initiate the infection of their corresponding bacterial host and act as the primary determinant for host specificity. The ever-increasing amount of sequence data enables the development of predictive models for the automated identification of RBP sequences. However, the development of such models is challenged by the inconsistent or missing annotation of many phage proteins. Recently developed tools have started to bridge this gap but are not specifically focused on RBP sequences, for which many different annotations are available. We have developed two parallel approaches to alleviate the complex identification of RBP sequences in phage genomic data. The first combines known RBP-related hidden Markov models (HMMs) from the Pfam database with custom-built HMMs to identify phage RBPs based on protein domains. The second approach consists of training an extreme gradient boosting classifier that can accurately discriminate between RBPs and other phage proteins. We explained how these complementary approaches can reinforce each other in identifying RBP sequences. In addition, we benchmarked our methods against the recently developed PhANNs tool. Our best performing model reached a precision-recall area-under-the-curve of 93.8% and outperformed PhANNs on an independent test set, reaching an F1-score of 84.0% compared to 69.8%. Full article

(This article belongs to the Special Issue Virus Bioinformatics 2022)

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11 pages, 1443 KiB

Open AccessArticle

Human Intramuscular Hyperimmune Gamma Globulin (hIHGG) Anti-SARS-CoV-2—Characteristics of Intermediates and Final Product

by Elzbieta Lachert, Joanna Lasocka, Artur Bielawski, Ewa Sulkowska, Katarzyna Guz, Krzysztof Pyrc, Agnieszka Dabrowska, Agata Wawryniuk-Malmon, Magdalena Letowska, Krzysztof Tomasiewicz and Piotr Grabarczyk

Viruses 2022, 14(6), 1328; https://doi.org/10.3390/v14061328 - 17 Jun 2022

Cited by 2 | Viewed by 2739

Abstract

This study aims to characterize the intermediates, and the final product (FP) obtained during the production of human intramuscular hyperimmune gamma globulin anti-SARS-CoV-2 (hIHGG anti-SARS-CoV-2) and to determine its stability. Material and methods: hIHGG anti-SARS-CoV-2 was fractionated from 270 convalescent plasma donations [...] Read more.

This study aims to characterize the intermediates, and the final product (FP) obtained during the production of human intramuscular hyperimmune gamma globulin anti-SARS-CoV-2 (hIHGG anti-SARS-CoV-2) and to determine its stability. Material and methods: hIHGG anti-SARS-CoV-2 was fractionated from 270 convalescent plasma donations with the Cohn method. Prior to fractionation, the plasma was inactivated (Theraflex MB Plasma). Samples were defined using enzyme immunoassays (EIA) for anti-S1, anti-RBD S1, and anti-N antibodies, and neutralization assays with SARS-CoV-2 (VN) and pseudoviruses (PVN, decorated with SARS-CoV-2 S protein). Results were expressed as a titer (EIA) or 50% of the neutralization titer (IC₅₀) estimated in a four-parameter nonlinear regression model. Results: Concentration of anti-S1 antibodies in plasma was similar before and after inactivation. Following fractionation, the anti-S1, anti-RBD, and anti-N (total tests) titers in FP were concentrated approximately 15-fold from 1:4 to 1:63 (1800 BAU/mL), 7-fold from 1:111 to 1:802 and from 1:13 to 1:88, respectively. During production, the IgA (anti-S1) antibody titer was reduced to an undetectable level and the IgM (anti-RBD) titer from 1:115 to 1:24. The neutralizing antibodies (nAb) titer increased in both VN (from 1:40 to 1:160) and PVN (IC₅₀ from 63 to 313). The concentration of specific IgG in the FP did not change significantly for 14 months. Conclusions: The hIHGG anti-SARS-CoV-2 was stable, with concentration up to approximately 15-fold nAb compared to the source plasma pool. Full article

(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)

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20 pages, 3353 KiB

Open AccessArticle

Expression of Alphavirus Nonstructural Protein 2 (nsP2) in Mosquito Cells Inhibits Viral RNA Replication in Both a Protease Activity-Dependent and -Independent Manner

by Liubov Cherkashchenko, Kai Rausalu, Sanjay Basu, Luke Alphey and Andres Merits

Viruses 2022, 14(6), 1327; https://doi.org/10.3390/v14061327 - 17 Jun 2022

Cited by 8 | Viewed by 3099

Abstract

Alphaviruses are positive-strand RNA viruses, mostly being mosquito-transmitted. Cells infected by an alphavirus become resistant to superinfection due to a block that occurs at the level of RNA replication. Alphavirus replication proteins, called nsP1-4, are produced from nonstructural polyprotein precursors, processed by the [...] Read more.

Alphaviruses are positive-strand RNA viruses, mostly being mosquito-transmitted. Cells infected by an alphavirus become resistant to superinfection due to a block that occurs at the level of RNA replication. Alphavirus replication proteins, called nsP1-4, are produced from nonstructural polyprotein precursors, processed by the protease activity of nsP2. Trans-replicase systems and replicon vectors were used to study effects of nsP2 of chikungunya virus and Sindbis virus on alphavirus RNA replication in mosquito cells. Co-expressed wild-type nsP2 reduced RNA replicase activity of homologous virus; this effect was reduced but typically not abolished by mutation in the protease active site of nsP2. Mutations in the replicase polyprotein that blocked its cleavage by nsP2 reduced the negative effect of nsP2 co-expression, confirming that nsP2-mediated inhibition of RNA replicase activity is largely due to nsP2-mediated processing of the nonstructural polyprotein. Co-expression of nsP2 also suppressed the activity of replicases of heterologous alphaviruses. Thus, the presence of nsP2 inhibits formation and activity of alphavirus RNA replicase in protease activity-dependent and -independent manners. This knowledge improves our understanding about mechanisms of superinfection exclusion for alphaviruses and may aid the development of anti-alphavirus approaches. Full article

(This article belongs to the Section Animal Viruses)

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13 pages, 2437 KiB

Open AccessArticle

ORFeome Phage Display Reveals a Major Immunogenic Epitope on the S2 Subdomain of SARS-CoV-2 Spike Protein

by Rico Ballmann, Sven-Kevin Hotop, Federico Bertoglio, Stephan Steinke, Philip Alexander Heine, M. Zeeshan Chaudhry, Dieter Jahn, Boas Pucker, Fausto Baldanti, Antonio Piralla, Maren Schubert, Luka Čičin-Šain, Mark Brönstrup, Michael Hust and Stefan Dübel

Viruses 2022, 14(6), 1326; https://doi.org/10.3390/v14061326 - 17 Jun 2022

Cited by 7 | Viewed by 3196

Abstract

The development of antibody therapies against SARS-CoV-2 remains a challenging task during the ongoing COVID-19 pandemic. All approved therapeutic antibodies are directed against the receptor binding domain (RBD) of the spike, and therefore lose neutralization efficacy against emerging SARS-CoV-2 variants, which frequently mutate [...] Read more.

The development of antibody therapies against SARS-CoV-2 remains a challenging task during the ongoing COVID-19 pandemic. All approved therapeutic antibodies are directed against the receptor binding domain (RBD) of the spike, and therefore lose neutralization efficacy against emerging SARS-CoV-2 variants, which frequently mutate in the RBD region. Previously, phage display has been used to identify epitopes of antibody responses against several diseases. Such epitopes have been applied to design vaccines or neutralize antibodies. Here, we constructed an ORFeome phage display library for the SARS-CoV-2 genome. Open reading frames (ORFs) representing the SARS-CoV-2 genome were displayed on the surface of phage particles in order to identify enriched immunogenic epitopes from COVID-19 patients. Library quality was assessed by both NGS and epitope mapping of a monoclonal antibody with a known binding site. The most prominent epitope captured represented parts of the fusion peptide (FP) of the spike. It is associated with the cell entry mechanism of SARS-CoV-2 into the host cell; the serine protease TMPRSS2 cleaves the spike within this sequence. Blocking this mechanism could be a potential target for non-RBD binding therapeutic anti-SARS-CoV-2 antibodies. As mutations within the FP amino acid sequence have been rather rare among SARS-CoV-2 variants so far, this may provide an advantage in the fight against future virus variants. Full article

(This article belongs to the Section Bacterial Viruses)

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12 pages, 1284 KiB

Open AccessReview

Direct-Acting Antiviral Agents for Hepatitis C Virus Infection—From Drug Discovery to Successful Implementation in Clinical Practice

by Christopher Dietz and Benjamin Maasoumy

Viruses 2022, 14(6), 1325; https://doi.org/10.3390/v14061325 - 17 Jun 2022

Cited by 20 | Viewed by 3832

Abstract

Today, hepatitis C virus infection affects up to 1.5 million people per year and is responsible for 29 thousand deaths per year. In the 1970s, the clinical observation of unclear, transfusion-related cases of hepatitis ignited scientific curiosity, and after years of intensive, basic [...] Read more.

Today, hepatitis C virus infection affects up to 1.5 million people per year and is responsible for 29 thousand deaths per year. In the 1970s, the clinical observation of unclear, transfusion-related cases of hepatitis ignited scientific curiosity, and after years of intensive, basic research, the hepatitis C virus was discovered and described as the causative agent for these cases of unclear hepatitis in 1989. Even before the description of the hepatitis C virus, clinicians had started treating infected individuals with interferon. However, intense side effects and limited antiviral efficacy have been major challenges, shaping the aim for the development of more suitable and specific treatments. Before direct-acting antiviral agents could be developed, a detailed understanding of viral properties was necessary. In the years after the discovery of the new virus, several research groups had been working on the hepatitis C virus biology and finally revealed the replication cycle. This knowledge was the basis for the later development of specific antiviral drugs referred to as direct-acting antiviral agents. In 2011, roughly 22 years after the discovery of the hepatitis C virus, the first two drugs became available and paved the way for a revolution in hepatitis C therapy. Today, the treatment of chronic hepatitis C virus infection does not rely on interferon anymore, and the treatment response rate is above 90% in most cases, including those with unsuccessful pretreatments. Regardless of the clinical and scientific success story, some challenges remain until the HCV elimination goals announced by the World Health Organization are met. Full article

(This article belongs to the Special Issue Antiviral Molecular Mechanisms)

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15 pages, 2944 KiB

Open AccessArticle

Palmitoylation Is Indispensable for Remorin to Restrict Tobacco Mosaic Virus Cell-to-Cell Movement in Nicotiana benthamiana

by Tingting Ma, Shuai Fu, Kun Wang, Yaqin Wang, Jianxiang Wu and Xueping Zhou

Viruses 2022, 14(6), 1324; https://doi.org/10.3390/v14061324 - 17 Jun 2022

Cited by 4 | Viewed by 2385

Abstract

Remorin (REM) is a plant-specific plasma membrane-associated protein regulating plasmodesmata plasticity and restricting viral cell-to-cell movement. Here, we show that palmitoylation is broadly present in group 1 remorin proteins in Nicotiana benthamiana and is crucial for plasma membrane localization and accumulation. By screening [...] Read more.

Remorin (REM) is a plant-specific plasma membrane-associated protein regulating plasmodesmata plasticity and restricting viral cell-to-cell movement. Here, we show that palmitoylation is broadly present in group 1 remorin proteins in Nicotiana benthamiana and is crucial for plasma membrane localization and accumulation. By screening the four members of N. benthamiana group 1 remorin proteins, we found that only NbREM1.5 could significantly hamper tobacco mosaic virus (TMV) cell-to-cell movement. We further showed that NbREM1.5 interacts with the movement protein of TMV in vivo and interferes with its function of expanding the plasmodesmata size exclusion limit. We also demonstrated that palmitoylation is indispensable for NbREM1.5 to hamper plasmodesmata permeability and inhibit TMV cell-to-cell movement. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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23 pages, 982 KiB

Open AccessReview

Influenza B: Prospects for the Development of Cross-Protective Vaccines

by Liudmila M. Tsybalova, Liudmila A. Stepanova, Edward S. Ramsay and Andrey V. Vasin

Viruses 2022, 14(6), 1323; https://doi.org/10.3390/v14061323 - 17 Jun 2022

Cited by 13 | Viewed by 3537

Abstract

In this review, we analyze the epidemiological and ecological features of influenza B, one of the most common and severe respiratory infections. The review presents various strategies for cross-protective influenza B vaccine development, including recombinant viruses, virus-like particles, and recombinant proteins. We provide [...] Read more.

In this review, we analyze the epidemiological and ecological features of influenza B, one of the most common and severe respiratory infections. The review presents various strategies for cross-protective influenza B vaccine development, including recombinant viruses, virus-like particles, and recombinant proteins. We provide an overview of viral proteins as cross-protective vaccine targets, along with other updated broadly protective vaccine strategies. The importance of developing such vaccines lies not only in influenza B prevention, but also in the very attractive prospect of eradicating the influenza B virus in the human population. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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12 pages, 575 KiB

Open AccessReview

Cardiac Complications of COVID-19 in Low-Risk Patients

by Akash Srinivasan, Felyx Wong, Liam S. Couch and Brian X. Wang

Viruses 2022, 14(6), 1322; https://doi.org/10.3390/v14061322 - 17 Jun 2022

Cited by 11 | Viewed by 5369

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has resulted in over 6 million deaths and significant morbidity across the globe. Alongside common respiratory symptoms, COVID-19 is associated with a variety of cardiovascular complications in the acute and post-acute phases of infection. The suggested pathophysiological [...] Read more.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in over 6 million deaths and significant morbidity across the globe. Alongside common respiratory symptoms, COVID-19 is associated with a variety of cardiovascular complications in the acute and post-acute phases of infection. The suggested pathophysiological mechanisms that underlie these complications include direct viral infection of the myocardium via the angiotensin-converting enzyme 2 (ACE2) protein and a cytokine release syndrome that results in indirect inflammatory damage to the heart. Patients with pre-existing cardiovascular disease and co-morbidities are generally more susceptible to the cardiac manifestations of COVID-19. However, studies have identified a variety of complications in low-risk individuals, including young adults and children. Myocarditis and paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS) are among the adverse events reported in the acute phase of infection. Furthermore, patients have reported cardiac symptoms persisting beyond the acute phase in post-COVID syndrome. This review summarises the acute and chronic cardiac consequences of COVID-19 in low-risk patients, explores the pathophysiology behind them, and discusses new predictive factors for poor outcomes. Full article

(This article belongs to the Special Issue Post-COVID Syndrome)

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16 pages, 1799 KiB

Open AccessArticle

A Novel Class of HIV-1 Inhibitors Targeting the Vpr-Induced G2-Arrest in Macrophages by New Yeast- and Cell-Based High-Throughput Screening

by Hirotaka Sato, Tomoyuki Murakami, Ryosuke Matsuura, Masako Abe, Seiji Matsuoka, Yoko Yashiroda, Minoru Yoshida, Hirofumi Akari, Yosuke Nagasawa, Masami Takei and Yoko Aida

Viruses 2022, 14(6), 1321; https://doi.org/10.3390/v14061321 - 16 Jun 2022

Cited by 2 | Viewed by 3070

Abstract

The human immunodeficiency virus type 1 (HIV-1) accessory protein, Vpr, arrests the cell cycle of the G2 phase, and this Vpr-mediated G2 arrest is implicated in an efficient HIV-1 spread in monocyte-derived macrophages. Here, we screened new candidates for Vpr-targeting HIV-1 inhibitors by [...] Read more.

The human immunodeficiency virus type 1 (HIV-1) accessory protein, Vpr, arrests the cell cycle of the G2 phase, and this Vpr-mediated G2 arrest is implicated in an efficient HIV-1 spread in monocyte-derived macrophages. Here, we screened new candidates for Vpr-targeting HIV-1 inhibitors by using fission yeast- and mammalian cell-based high-throughput screening. First, fission yeast strains expressing the HIV-1 Vpr protein were generated and then treated for 48 h with 20 μM of a synthetic library, including 140,000 chemical compounds. We identified 268 compounds that recovered the growth of Vpr-overexpressing yeast. The selected compounds were then tested in mammalian cells, and those displaying high cytotoxicity were excluded from further cell cycle analysis and imaging-based screening. A flow cytometry analysis confirmed that seven compounds recovered from the Vpr-induced G2 arrest. The cell toxicity and inhibitory effect of HIV-1 replication in human monocyte-derived macrophages (MDM) were examined, and three independent structural compounds, VTD227, VTD232, and VTD263, were able to inhibit HIV-1 replication in MDM. Furthermore, we showed that VTD227, but not VTD232 and VTD263, can directly bind to Vpr. Our results indicate that three new compounds and their derivatives represent new drugs targeting HIV-1 replication and can be potentially used in clinics to improve the current antiretroviral therapy. Full article

(This article belongs to the Special Issue Viral Accessory Proteins)

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16 pages, 1688 KiB

Open AccessArticle

A Novel Flavi-like Virus in Alfalfa (Medicago sativa L.) Crops along the Snake River Valley

by Jennifer Dahan, Yuri I. Wolf, Gardenia E. Orellana, Erik J. Wenninger, Eugene V. Koonin and Alexander V. Karasev

Viruses 2022, 14(6), 1320; https://doi.org/10.3390/v14061320 - 16 Jun 2022

Cited by 8 | Viewed by 3693

Abstract

Alfalfa is an important perennial forage crop in Idaho supporting dairy and cattle industries that is typically grown in the same field for as many as 4 years. Alfalfa stands of different ages were subjected to screening for viruses using high-throughput sequencing and [...] Read more.

Alfalfa is an important perennial forage crop in Idaho supporting dairy and cattle industries that is typically grown in the same field for as many as 4 years. Alfalfa stands of different ages were subjected to screening for viruses using high-throughput sequencing and RT-PCR. The two most common viruses found were alfalfa mosaic virus and bean leafroll virus, along with Medicago sativa amalgavirus, two alphapartitiviruses, and one deltapartitivirus. Additionally, a new flavi-like virus with an unusual genome organization was discovered, dubbed Snake River alfalfa virus (SRAV). The 11,745 nt, positive-sense (+) RNA genome of SRAV encodes a single 3835 aa polyprotein with only two identifiable conserved domains, an RNA-dependent RNA polymerase (RdRP) and a predicted serine protease. Notably, unlike all +RNA virus genomes in the similar size range, the SRAV polyprotein contained no predicted helicase domain. In the RdRP phylogeny, SRAV was placed inside the flavi-like lineage as a sister clade to a branch consisting of hepaci-, and pegiviruses. To the best of our knowledge, SRAV is the first flavi-like virus identified in a plant host. Although commonly detected in alfalfa crops in southern Idaho, SRAV sequences were also amplified from thrips feeding in alfalfa stands in the area, suggesting a possible role of Frankliniella occidentalis in virus transmission. Full article

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

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20 pages, 4540 KiB

Open AccessArticle

Pathogenesis of West Nile Virus Lineage 2 in Domestic Geese after Experimental Infection

by Hannah Reemtsma, Cora M. Holicki, Christine Fast, Felicitas Bergmann, Martin Eiden, Martin H. Groschup and Ute Ziegler

Viruses 2022, 14(6), 1319; https://doi.org/10.3390/v14061319 - 16 Jun 2022

Cited by 6 | Viewed by 2755

Abstract

West Nile virus (WNV) is an emerging infectious pathogen circulating between mosquitoes and birds but also infecting mammals. WNV has become autochthonous in Germany, causing striking mortality rates in avifauna and occasional diseases in humans and horses. We therefore wanted to assess the [...] Read more.

West Nile virus (WNV) is an emerging infectious pathogen circulating between mosquitoes and birds but also infecting mammals. WNV has become autochthonous in Germany, causing striking mortality rates in avifauna and occasional diseases in humans and horses. We therefore wanted to assess the possible role of free-ranging poultry in the WNV transmission cycle and infected 15 goslings with WNV lineage 2 (German isolate). The geese were monitored daily and sampled regularly to determine viremia, viral shedding, and antibody development by molecular and serological methods. Geese were euthanized at various time points post-infection (pi). All infected geese developed variable degrees of viremia from day 1 to day 10 (maximum) and actively shed virus from days 2 to 7 post-infection. Depending on the time of death, the WN viral genome was detected in all examined tissue samples in at least one individual by RT-qPCR and viable virus was even re-isolated, except for in the liver. Pathomorphological lesions as well as immunohistochemically detectable viral antigens were found mainly in the brain. Furthermore, all of the geese seroconverted 6 days pi at the latest. In conclusion, geese are presumably not functioning as important amplifying hosts but are suitable sentinel animals for WNV surveillance. Full article

(This article belongs to the Special Issue Flaviviruses and Flavivirus Vaccines)

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15 pages, 1264 KiB

Open AccessArticle

Genomic Epidemiology of SARS-CoV-2 in Seychelles, 2020–2021

by John Mwita Morobe, Brigitte Pool, Lina Marie, Dwayne Didon, Arnold W. Lambisia, Timothy Makori, Khadija Said Mohammed, Zaydah R. de Laurent, Leonard Ndwiga, Maureen W. Mburu, Edidah Moraa, Nickson Murunga, Jennifer Musyoki, Jedida Mwacharo, Lydia Nyamako, Debra Riako, Pariken Ephnatus, Faith Gambo, Josephine Naimani, Joyce Namulondo, Susan Zimba Tembo, Edwin Ogendi, Thierno Balde, Fred Athanasius Dratibi, Ali Ahmed Yahaya, Nicksy Gumede, Rachel A. Achilla, Peter K. Borus, Dorcas W. Wanjohi, Sofonias K. Tessema, Joseph Mwangangi, Philip Bejon, David J. Nokes, Lynette Isabella Ochola-Oyier, George Githinji, Leon Biscornet and Charles N. Agoti Show full author list Hide full author list

Viruses 2022, 14(6), 1318; https://doi.org/10.3390/v14061318 - 16 Jun 2022

Cited by 4 | Viewed by 3223

Abstract

Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st of December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but [...] Read more.

Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st of December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but cases remained low until January 2021, when a surge was observed. Here, we investigated the potential drivers of the surge by genomic analysis of 1056 SARS-CoV-2 positive samples collected in Seychelles between 14 March 2020 and 31 December 2021. The Seychelles genomes were classified into 32 Pango lineages, 1042 of which fell within four variants of concern, i.e., Alpha, Beta, Delta and Omicron. Sporadic cases of SARS-CoV-2 detected in Seychelles in 2020 were mainly of lineage B.1 (lineage predominantly observed in Europe) but this lineage was rapidly replaced by Beta variant starting January 2021, and which was also subsequently replaced by the Delta variant in May 2021 that dominated till November 2021 when Omicron cases were identified. Using the ancestral state reconstruction approach, we estimated that at least 78 independent SARS-CoV-2 introduction events occurred in Seychelles during the study period. The majority of viral introductions into Seychelles occurred in 2021, despite substantial COVID-19 restrictions in place during this period. We conclude that the surge of SARS-CoV-2 cases in Seychelles in January 2021 was primarily due to the introduction of more transmissible SARS-CoV-2 variants into the islands. Full article

(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)

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15 pages, 1198 KiB

Open AccessReview

Prevention and Control of Porcine Epidemic Diarrhea: The Development of Recombination-Resistant Live Attenuated Vaccines

by Xiaoyu Niu and Qiuhong Wang

Viruses 2022, 14(6), 1317; https://doi.org/10.3390/v14061317 - 16 Jun 2022

Cited by 19 | Viewed by 3518

Abstract

Porcine epidemic diarrhea (PED), causing up to 100% mortality in neonatal pigs, is a highly contagious enteric disease caused by PED virus (PEDV). The highly virulent genogroup 2 (G2) PEDV emerged in 2010 and has caused huge economic losses to the pork industry [...] Read more.

Porcine epidemic diarrhea (PED), causing up to 100% mortality in neonatal pigs, is a highly contagious enteric disease caused by PED virus (PEDV). The highly virulent genogroup 2 (G2) PEDV emerged in 2010 and has caused huge economic losses to the pork industry globally. It was first reported in the US in 2013, caused country-wide outbreaks, and posed tremendous hardship for many pork producers in 2013–2014. Vaccination of pregnant sows/gilts with live attenuated vaccines (LAVs) is the most effective strategy to induce lactogenic immunity in the sows/gilts and provide a passive protection via the colostrum and milk to suckling piglets against PED. However, there are still no safe and effective vaccines available after about one decade of endeavor. One of the biggest concerns is the potential reversion to virulence of an LAV in the field. In this review, we summarize the status and the major obstacles in PEDV LAV development. We also discuss the function of the transcriptional regulatory sequences in PEDV transcription, contributing to recombination, and possible strategies to prevent the reversion of LAVs. This article provides insights into the rational design of a promising LAV without safety issues. Full article

(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)

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