Viruses

20 pages, 4997 KiB

Open AccessReview

How Antibodies Recognize Pathogenic Viruses: Structural Correlates of Antibody Neutralization of HIV-1, SARS-CoV-2, and Zika

by Morgan E. Abernathy, Kim-Marie A. Dam, Shannon R. Esswein, Claudia A. Jette and Pamela J. Bjorkman

Viruses 2021, 13(10), 2106; https://doi.org/10.3390/v13102106 - 19 Oct 2021

Cited by 8 | Viewed by 6151

Abstract

The H1N1 pandemic of 2009-2010, MERS epidemic of 2012, Ebola epidemics of 2013-2016 and 2018-2020, Zika epidemic of 2015-2016, and COVID-19 pandemic of 2019-2021, are recent examples in the long history of epidemics that demonstrate the enormous global impact of viral infection. The [...] Read more.

The H1N1 pandemic of 2009-2010, MERS epidemic of 2012, Ebola epidemics of 2013-2016 and 2018-2020, Zika epidemic of 2015-2016, and COVID-19 pandemic of 2019-2021, are recent examples in the long history of epidemics that demonstrate the enormous global impact of viral infection. The rapid development of safe and effective vaccines and therapeutics has proven vital to reducing morbidity and mortality from newly emerging viruses. Structural biology methods can be used to determine how antibodies elicited during infection or vaccination target viral proteins and identify viral epitopes that correlate with potent neutralization. Here we review how structural and molecular biology approaches have contributed to our understanding of antibody recognition of pathogenic viruses, specifically HIV-1, SARS-CoV-2, and Zika. Determining structural correlates of neutralization of viruses has guided the design of vaccines, monoclonal antibodies, and small molecule inhibitors in response to the global threat of viral epidemics. Full article

(This article belongs to the Special Issue Rosalind Franklin's 100th Birthday)

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12 pages, 769 KiB

Open AccessArticle

Sero-Epidemiological Survey of Orthopoxvirus in Stray Cats and in Different Domestic, Wild and Exotic Animal Species of Central Italy

by Francesca Rosone, Marcello Giovanni Sala, Giusy Cardeti, Pasquale Rombolà, Marina Cittadini, Azzurra Carnio, Roberta Giordani and Maria Teresa Scicluna

Viruses 2021, 13(10), 2105; https://doi.org/10.3390/v13102105 - 19 Oct 2021

Cited by 2 | Viewed by 2267

Abstract

Orthpoxvirus infection can spread more easily in a population with a waning immunity with the subsequent emergence/re-emergence of the viruses pertaining to this genus. In the last two decades, several cases of Orthopoxvirus, and in particular Cowpoxvirus infections in humans were reported in [...] Read more.

Orthpoxvirus infection can spread more easily in a population with a waning immunity with the subsequent emergence/re-emergence of the viruses pertaining to this genus. In the last two decades, several cases of Orthopoxvirus, and in particular Cowpoxvirus infections in humans were reported in different parts of the world, possibly due to the suspension of smallpox vaccinations. To date, in Italy, few investigations were conducted on the presence of these infections, and because of this a serosurvey was carried out to evaluate Cowpoxvirus infection in feline colonies situated in the province of Rome, since these are also susceptible to other zoonotic viruses belonging to Orthopoxvirus, and from which humans may contract the infection. The sample design was set at an expected minimum seroprevalence of 7.5%, a 5% standard error and 95% confidence level. In parallel, a serological investigation was conducted using convenience sampling in domestic, exotic and wild susceptible animals of the Latium and Tuscany Regions, which are areas in the jurisdiction of the Istituto Zooprofilattico Sperimentale del Lazio e della Toscana, coordinating this study. The serological methods employed were indirect immunofluorescence for 36 sera of nonhuman primate and virus neutralization for 1198 sera of different species. All the 1234 sera examined were negative for the presence of antibodies against Cowpoxvirus, indicating its limited circulation in the areas of investigation. The methodology applied for the serosurveillance could be adopted in the case of outbreaks of this infection and for the evaluation of the spread of this infection in the area of interest, to obtain essential information crucial for animal and public health policies according to the One Health concept. Full article

(This article belongs to the Special Issue Ecology of Virus Emergence from Wildlife)

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9 pages, 11859 KiB

Open AccessArticle

Near-Complete Genome of SARS-CoV-2 Delta (AY.3) Variant Identified in a Dog in Kansas, USA

by Tyler Doerksen, Andrea Lu, Lance Noll, Kelli Almes, Jianfa Bai, David Upchurch and Rachel Palinski

Viruses 2021, 13(10), 2104; https://doi.org/10.3390/v13102104 - 19 Oct 2021

Cited by 15 | Viewed by 4888

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) descriptions of infection and transmission have been increasing in companion animals in the past year. Although canine susceptibility is generally considered low, their role in the COVID-19 disease cycle remains unknown. In this study, we detected [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) descriptions of infection and transmission have been increasing in companion animals in the past year. Although canine susceptibility is generally considered low, their role in the COVID-19 disease cycle remains unknown. In this study, we detected and sequenced a delta variant (AY.3) from a 12-year-old Collie living with owners that previously tested positive for SARS-CoV-2. It is unclear if the dogs’ symptoms were related to SARS-CoV-2 infection or underlying conditions. The whole genome sequence obtained from the dog sample had several unique consensus level changes not previously identified in a SARS-CoV-2 genome that may play a role in the rapid adaptation from humans to dogs. Within the spike coding region, 5/7 of the subconsensus variants identified in the dog sequence were also identified in the closest in-house human reference case. Taken together, the whole genome sequence, and phylogenetic and subconsensus variant analyses indicate the virus infecting the animal originated from a local outbreak cluster. The results of these analyses emphasize the importance of rapid detection and characterization of SARS-CoV-2 variants of concern in companion animals. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 2141 KiB

Open AccessArticle

Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKV^BR in Mice Bearing Embryonal CNS Tumors

by Raiane Oliveira Ferreira, Isabela Granha, Rodolfo Sanches Ferreira, Heloisa de Siqueira Bueno, Oswaldo Keith Okamoto, Carolini Kaid and Mayana Zatz

Viruses 2021, 13(10), 2103; https://doi.org/10.3390/v13102103 - 19 Oct 2021

Cited by 10 | Viewed by 8399

Abstract

The Zika virus (ZIKV) has shown a promising oncolytic effect against embryonal CNS tumors. However, studies on the effect of different administration routes and the ideal viral load in preclinical models are highly relevant aiming for treatment safety and efficiency. Here, we investigated [...] Read more.

The Zika virus (ZIKV) has shown a promising oncolytic effect against embryonal CNS tumors. However, studies on the effect of different administration routes and the ideal viral load in preclinical models are highly relevant aiming for treatment safety and efficiency. Here, we investigated the effect and effectiveness of different routes of administration, and the number of ZIKV^BR injections on tumor tropism, destruction, and side effects. Furthermore, we designed an early-stage human brain organoid co-cultured with embryonal CNS tumors to analyze the ZIKV^BR oncolytic effect. We showed that in the mice bearing subcutaneous tumors, the ZIKV^BR systemically presented a tropism to the brain. When the tumor was located in the mice’s brain, serial systemic injections presented efficient tumor destruction, with no neurological or other organ injury and increased mice survival. In the human cerebral organoid model co-cultured with embryonal CNS tumor cells, ZIKV^BR impaired tumor progression. The gene expression of cytokines and chemokines in both models suggested an enhancement of immune cells recruitment and tumor inflammation after the treatment. These results open new perspectives for virotherapy using the ZIKV^BR systemic administration route and multiple doses of low virus load for safe and effective treatment of embryonal CNS tumors, an orphan disease that urges new effective therapies. Full article

(This article belongs to the Special Issue Viral Infection of Neural Stem Cells)

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14 pages, 1830 KiB

Open AccessArticle

Assessment of Cidofovir for Treatment of Ocular Bovine Herpesvirus-1 Infection in Cattle Using an Ex-Vivo Model

by Christopher R. Alling, Chin-Chi Liu, Ingeborg M. Langohr, Muzammel Haque, Renee T. Carter, Rose E. Baker and Andrew C. Lewin

Viruses 2021, 13(10), 2102; https://doi.org/10.3390/v13102102 - 18 Oct 2021

Cited by 2 | Viewed by 3082

Abstract

Bovine herpesvirus-1 (BoHV-1) infection contributes to keratoconjunctivitis, respiratory disease, and reproductive losses in cattle. The objective of this study was to determine the most appropriate ophthalmic antiviral agent for BoHV-1 inhibition using in-vitro culture and novel ex-vivo bovine corneal modeling. Half-maximal inhibitory concentrations [...] Read more.

Bovine herpesvirus-1 (BoHV-1) infection contributes to keratoconjunctivitis, respiratory disease, and reproductive losses in cattle. The objective of this study was to determine the most appropriate ophthalmic antiviral agent for BoHV-1 inhibition using in-vitro culture and novel ex-vivo bovine corneal modeling. Half-maximal inhibitory concentrations of BoHV-1 were determined for cidofovir, ganciclovir, idoxuridine, and trifluridine via in-vitro plaque reduction assays. In-vitro cytotoxicity was compared amongst these compounds via luciferase assays. Trifluridine and cidofovir were the most potent BoHV-1 inhibitors in vitro, while trifluridine and idoxuridine were the most cytotoxic agents. Therefore, cidofovir was the most potent non-cytotoxic agent and was employed in the ex-vivo corneal assay. Corneoscleral rings (n = 36) from fresh cadaver bovine globes were harvested and equally divided into an uninfected, untreated control group; a BoHV-1-infected, untreated group; and a BoHV-1-infected, cidofovir-treated group. Virus isolation for BoHV-1 titers was performed from corneal tissue and liquid media. Histologic measurements of corneal thickness, epithelial cell density, and tissue organization were compared between groups. Substantial BoHV-1 replication was observed in infected, untreated corneas, but BoHV-1 titer was significantly reduced in cidofovir-treated (1.69 ± 0.08 × 10³ PFU/mL) versus untreated (8.25 ± 0.25 × 10⁵ PFU/mL, p < 0.0001) tissues by day 2 of culture. No significant differences in histologic criteria were observed between groups. In conclusion, cidofovir warrants further investigation as treatment for BoHV-1 keratoconjunctivitis, with future studies needed to assess in-vivo tolerability and efficacy. Full article

(This article belongs to the Special Issue Enteric and Respiratory Viruses in Animals)

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13 pages, 1784 KiB

Open AccessArticle

Prolonged Gut Dysbiosis and Fecal Excretion of Hepatitis A Virus in Patients Infected with Human Immunodeficiency Virus

by Aya Ishizaka, Michiko Koga, Taketoshi Mizutani, Lay Ahyoung Lim, Eisuke Adachi, Kazuhiko Ikeuchi, Ryuta Ueda, Haruyo Aoyagi, Satoshi Tanaka, Hiroshi Kiyono, Tetsuro Matano, Hideki Aizaki, Sachiyo Yoshio, Eiji Mita, Masamichi Muramatsu, Tatsuya Kanto, Takeya Tsutsumi and Hiroshi Yotsuyanagi

Viruses 2021, 13(10), 2101; https://doi.org/10.3390/v13102101 - 18 Oct 2021

Cited by 12 | Viewed by 3272

Abstract

Hepatitis A virus (HAV) causes transient acute infection, and little is known of viral shedding via the duodenum and into the intestinal environment, including the gut microbiome, from the period of infection until after the recovery of symptoms. Therefore, in this study, we [...] Read more.

Hepatitis A virus (HAV) causes transient acute infection, and little is known of viral shedding via the duodenum and into the intestinal environment, including the gut microbiome, from the period of infection until after the recovery of symptoms. Therefore, in this study, we aimed to comprehensively observe the amount of virus excreted into the intestinal tract, the changes in the intestinal microbiome, and the level of inflammation during the healing process. We used blood and stool specimens from patients with human immunodeficiency virus who were infected with HAV during the HAV outbreak in Japan in 2018. Moreover, we observed changes in fecal HAV RNA and quantified the plasma cytokine level and gut microbiome by 16S rRNA analysis from clinical onset to at least 6 months after healing. HAV was detected from clinical onset up to a period of more than 150 days. Immediately after infection, many pro-inflammatory cytokines were elicited, and some cytokines showed different behaviors. The intestinal microbiome changed significantly after infection (dysbiosis), and the dysbiosis continued for a long time after healing. These observations suggest that the immunocompromised state is associated with prolonged viral shedding into the intestinal tract and delayed recovery of the intestinal environment. Full article

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

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11 pages, 2330 KiB

Open AccessArticle

Genome Editing of Rice eIF4G Loci Confers Partial Resistance to Rice Black-Streaked Dwarf Virus

by Wei Wang, Shuhui Ma, Peng Hu, Yinghua Ji and Feng Sun

Viruses 2021, 13(10), 2100; https://doi.org/10.3390/v13102100 - 18 Oct 2021

Cited by 20 | Viewed by 3716

Abstract

Rice black-streaked dwarf disease, caused by rice black-streaked dwarf virus (RBSDV), is a serious constraint in Chinese rice production. Breeding disease-resistant varieties through multigene aggregation is considered an effective way to control diseases, but few disease-resistant resources have been characterized thus far. To [...] Read more.

Rice black-streaked dwarf disease, caused by rice black-streaked dwarf virus (RBSDV), is a serious constraint in Chinese rice production. Breeding disease-resistant varieties through multigene aggregation is considered an effective way to control diseases, but few disease-resistant resources have been characterized thus far. To develop novel resources for resistance to RBSDV through CRISPR/Cas9-mediated genome editing, a guide RNA sequence targeting exon 1 of eIF4G was designed and cloned into a binary vector, pHUE401. This recombinant vector was used to generate mutations in the rice cultivar Nipponbare via Agrobacterium-mediated transformation. This approach produced heritable homozygous mutations in the transgene-free T1 generation. Sequence analysis of the eIF4G target region from T1 transgenic plants identified 3 bp deletion mutants, and analysis of the predicted amino acid sequence identified one amino acid deletion in mutants that possess near full-length eIF4G. Furthermore, our data suggest that eIF4G may plays an important role in rice normal development, as there were no eIF4G knock-out homozygous mutants in T1 generation plants. When homozygous mutant lines were inoculated with RBSDV, they exhibited enhanced tolerance to virus infection, without visibly affecting plant growth and development. However, the eif4g mutant plants showed the same sensitivity to rice stripe virus (RSV) infection as wild-type plants. Notably, the wild-type and mutant N-termini of eIF4G interacted directly with RBSDV P8 in yeast and in planta. Additionally, compared to wild-type plants, the eIF4G transcript level was reduced twofold in the mutant plants. These results indicate that site-specific mutation of rice eIF4G successfully conferred partial resistance specific to RBSDV associated with less transcription of eIF4G in mutants. Therefore, this study demonstrates that the novel eIF4G alleles generated by CRISPR/Cas9 represent valuable disease-resistant resources that can be used to develop RBSDV-resistant varieties. Full article

(This article belongs to the Special Issue State-of-the-Art Plant Virus Research in China)

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29 pages, 1278 KiB

Open AccessReview

Flavivirus Persistence in Wildlife Populations

by Maria Raisa Blahove and James Richard Carter

Viruses 2021, 13(10), 2099; https://doi.org/10.3390/v13102099 - 18 Oct 2021

Cited by 8 | Viewed by 5275

Abstract

A substantial number of humans are at risk for infection by vector-borne flaviviruses, resulting in considerable morbidity and mortality worldwide. These viruses also infect wildlife at a considerable rate, persistently cycling between ticks/mosquitoes and small mammals and reptiles and non-human primates and humans. [...] Read more.

A substantial number of humans are at risk for infection by vector-borne flaviviruses, resulting in considerable morbidity and mortality worldwide. These viruses also infect wildlife at a considerable rate, persistently cycling between ticks/mosquitoes and small mammals and reptiles and non-human primates and humans. Substantially increasing evidence of viral persistence in wildlife continues to be reported. In addition to in humans, viral persistence has been shown to establish in mammalian, reptile, arachnid, and mosquito systems, as well as insect cell lines. Although a considerable amount of research has centered on the potential roles of defective virus particles, autophagy and/or apoptosis-induced evasion of the immune response, and the precise mechanism of these features in flavivirus persistence have yet to be elucidated. In this review, we present findings that aid in understanding how vector-borne flavivirus persistence is established in wildlife. Research studies to be discussed include determining the critical roles universal flavivirus non-structural proteins played in flaviviral persistence, the advancement of animal models of viral persistence, and studying host factors that allow vector-borne flavivirus replication without destructive effects on infected cells. These findings underscore the viral–host relationships in wildlife animals and could be used to elucidate the underlying mechanisms responsible for the establishment of viral persistence in these animals. Full article

(This article belongs to the Special Issue Emerging Wildlife Viral Diseases)

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5 pages, 205 KiB

Open AccessEditorial

COVID-19 in 2021

by Kenneth Lundstrom and Alaa A. A. Aljabali

Viruses 2021, 13(10), 2098; https://doi.org/10.3390/v13102098 - 18 Oct 2021

Cited by 4 | Viewed by 3033

Abstract

The Special Issue on Vaccines and Therapeutics against Coronaviruses, which was launched in early 2021, has attracted the scientific community at large, and more than 20 manuscripts have been accepted for publication.[...] Full article

(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)

10 pages, 2022 KiB

Open AccessArticle

Analysis of SARS-CoV-2 Genomes from West Java, Indonesia

by Azzania Fibriani, Rebecca Stephanie, Afifah Alifia Alfiantie, Agust Leo Fany Siregar, Gusti Ayu Prani Pradani, Nicholas Yamahoki, William Steflandel Purba, Cut Nur Cinthia Alamanda, Ema Rahmawati, Rifky Waluyajati Rachman, Rini Robiani and Ryan Bayusantika Ristandi

Viruses 2021, 13(10), 2097; https://doi.org/10.3390/v13102097 - 18 Oct 2021

Cited by 16 | Viewed by 4955

Abstract

West Java Health Laboratory (WJHL) is one of the many institutions in Indonesia that have sequenced SARS-CoV-2 genome. Although having submitted a large number of sequences since September 2020, however, these submitted data lack advanced analyses. Therefore, in this study, we analyze the [...] Read more.

West Java Health Laboratory (WJHL) is one of the many institutions in Indonesia that have sequenced SARS-CoV-2 genome. Although having submitted a large number of sequences since September 2020, however, these submitted data lack advanced analyses. Therefore, in this study, we analyze the variant distribution, hotspot mutation, and its impact on protein structure and function of SARS-CoV-2 from the collected samples from WJHL. As many as one hundred sixty-three SARS-CoV-2 genome sequences submitted by West Java Health Laboratory (WJHL), with collection dates between September 2020 and June 2021, were retrieved from GISAID. Subsequently, the frequency and distribution of non-synonymous mutations across different cities and regencies from these samples were analyzed. The effect of the most prevalent mutations from dominant variants on the stability of their corresponding proteins was examined. The samples mostly consisted of people of working-age, and were distributed between female and male equally. All of the sample sequences showed varying levels of diversity, especially samples from West Bandung which carried the highest diversity. Dominant variants are the VOC B.1.617.2 (Delta) variant, B.1.466.2 variant, and B.1.470 variant. The genomic regions with the highest number of mutations are the spike, NSP3, nucleocapsid, NSP12, and ORF3a protein. Mutation analysis showed that mutations in structural protein might increase the stability of the protein. Oppositely, mutations in non-structural protein might lead to a decrease in protein stability. However, further research to study the impact of mutations on the function of SARS-CoV-2 proteins are required. Full article

(This article belongs to the Topic Burden of COVID-19 in Different Countries)

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16 pages, 2509 KiB

Open AccessReview

The Role of RASs /RVs in the Current Management of HCV

by Konstantinos Malandris, Georgios Kalopitas, Eleni Theocharidou and Georgios Germanidis

Viruses 2021, 13(10), 2096; https://doi.org/10.3390/v13102096 - 18 Oct 2021

Cited by 20 | Viewed by 2658

Abstract

The approval of combination therapies with direct-acting antiviral (DAA) regimens has led to significant progress in the field of hepatitis C virus (HCV) treatment. Although most patients treated with these agents achieve a virological cure, resistance to DAAs is a major issue. The [...] Read more.

The approval of combination therapies with direct-acting antiviral (DAA) regimens has led to significant progress in the field of hepatitis C virus (HCV) treatment. Although most patients treated with these agents achieve a virological cure, resistance to DAAs is a major issue. The rapid emergence of resistance-associated substitutions (RASs), in particular in the context of incomplete drug pressure, has an impact on sustained virological response (SVR) rates. Several RASs in NS3, NS5A and NS5B have been linked with reduced susceptibility to DAAs. RAS vary based on HCV characteristics and the different drug classes. DAA-resistant HCV variant haplotypes (RVs) are dominant in cases of virological failure. Viruses with resistance to NS3-4A protease inhibitors are only detected in the peripheral blood in a time frame ranging from weeks to months following completion of treatment, whereas NS5A inhibitor-resistant viruses may persist for years. Novel agents have been developed that demonstrate promising results in DAA-experienced patients. The recent approval of broad-spectrum drug combinations with a high genetic barrier to resistance and antiviral potency may overcome the problem of resistance. Full article

(This article belongs to the Special Issue Viral Resistance in HCV Infection)

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7 pages, 212 KiB

Open AccessPerspective

A Perspective on Nanotechnology and COVID-19 Vaccine Research and Production in South Africa

by Admire Dube, Samuel Egieyeh and Mohammed Balogun

Viruses 2021, 13(10), 2095; https://doi.org/10.3390/v13102095 - 18 Oct 2021

Cited by 6 | Viewed by 3207

Abstract

Advances in nanotechnology have enabled the development of a new generation of vaccines, which are playing a critical role in the global control of the COVID-19 pandemic and the return to normalcy. Vaccine development has been conducted, by and large, by countries in [...] Read more.

Advances in nanotechnology have enabled the development of a new generation of vaccines, which are playing a critical role in the global control of the COVID-19 pandemic and the return to normalcy. Vaccine development has been conducted, by and large, by countries in the global north. South Africa, as a major emerging economy, has made extensive investments in nanotechnology and bioinformatics and has the expertise and resources in vaccine development and manufacturing. This has been built at a national level through decades of investment. In this perspective article, we provide a synopsis of the investments made in nanotechnology and highlight how these could support innovation, research, and development for vaccines for this disease. We also discuss the application of bioinformatics tools to support rapid and cost-effective vaccine development and make recommendations for future research and development in this area to support future health challenges. Full article

(This article belongs to the Special Issue Coronaviruses Research in BRICS Countries)

17 pages, 4365 KiB

Open AccessArticle

Structural Studies of the Phage G Tail Demonstrate an Atypical Tail Contraction

by Brenda González, Daoyi Li, Kunpeng Li, Elena T. Wright, Stephen C. Hardies, Julie A. Thomas, Philip Serwer and Wen Jiang

Viruses 2021, 13(10), 2094; https://doi.org/10.3390/v13102094 - 18 Oct 2021

Cited by 5 | Viewed by 3067

Abstract

Phage G is recognized as having a remarkably large genome and capsid size among isolated, propagated phages. Negative stain electron microscopy of the host–phage G interaction reveals tail sheaths that are contracted towards the distal tip and decoupled from the head–neck region. This [...] Read more.

Phage G is recognized as having a remarkably large genome and capsid size among isolated, propagated phages. Negative stain electron microscopy of the host–phage G interaction reveals tail sheaths that are contracted towards the distal tip and decoupled from the head–neck region. This is different from the typical myophage tail contraction, where the sheath contracts upward, while being linked to the head–neck region. Our cryo-EM structures of the non-contracted and contracted tail sheath show that: (1) The protein fold of the sheath protein is very similar to its counterpart in smaller, contractile phages such as T4 and phi812; (2) Phage G’s sheath structure in the non-contracted and contracted states are similar to phage T4’s sheath structure. Similarity to other myophages is confirmed by a comparison-based study of the tail sheath’s helical symmetry, the sheath protein’s evolutionary timetree, and the organization of genes involved in tail morphogenesis. Atypical phase G tail contraction could be due to a missing anchor point at the upper end of the tail sheath that allows the decoupling of the sheath from the head–neck region. Explaining the atypical tail contraction requires further investigation of the phage G sheath anchor points. Full article

(This article belongs to the Special Issue Phage Assembly Pathways - to the Memory of Lindsay Black)

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19 pages, 2690 KiB

Open AccessArticle

Comparison of PCR versus PCR-Free DNA Library Preparation for Characterising the Human Faecal Virome

by Shen-Yuan Hsieh, Mohammad A. Tariq, Andrea Telatin, Rebecca Ansorge, Evelien M. Adriaenssens, George M. Savva, Catherine Booth, Tom Wileman, Lesley Hoyles and Simon R. Carding

Viruses 2021, 13(10), 2093; https://doi.org/10.3390/v13102093 - 18 Oct 2021

Cited by 8 | Viewed by 4620

Abstract

The human intestinal microbiota is abundant in viruses, comprising mainly bacteriophages, occasionally outnumbering bacteria 10:1 and is termed the virome. Due to their high genetic diversity and the lack of suitable tools and reference databases, the virome remains poorly characterised and is often [...] Read more.

The human intestinal microbiota is abundant in viruses, comprising mainly bacteriophages, occasionally outnumbering bacteria 10:1 and is termed the virome. Due to their high genetic diversity and the lack of suitable tools and reference databases, the virome remains poorly characterised and is often referred to as “viral dark matter”. However, the choice of sequencing platforms, read lengths and library preparation make study design challenging with respect to the virome. Here we have compared the use of PCR and PCR-free methods for sequence-library construction on the Illumina sequencing platform for characterising the human faecal virome. Viral DNA was extracted from faecal samples of three healthy donors and sequenced. Our analysis shows that most variation was reflecting the individually specific faecal virome. However, we observed differences between PCR and PCR-free library preparation that affected the recovery of low-abundance viral genomes. Using three faecal samples in this study, the PCR library preparation samples led to a loss of lower-abundance vOTUs evident in their PCR-free pairs (vOTUs 128, 6202 and 8364) and decreased the alpha-diversity indices (Chao1 p-value = 0.045 and Simpson p-value = 0.044). Thus, differences between PCR and PCR-free methods are important to consider when investigating “rare” members of the gut virome, with these biases likely negligible when investigating moderately and highly abundant viruses. Full article

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

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19 pages, 5996 KiB

Open AccessArticle

The Biogenesis of Dengue Virus Replication Organelles Requires the ATPase Activity of Valosin-Containing Protein

by Clément Mazeaud, Anaïs Anton, Felix Pahmeier, Aïssatou Aïcha Sow, Berati Cerikan, Wesley Freppel, Mirko Cortese, Ralf Bartenschlager and Laurent Chatel-Chaix

Viruses 2021, 13(10), 2092; https://doi.org/10.3390/v13102092 - 18 Oct 2021

Cited by 11 | Viewed by 4111

Abstract

The dengue virus (DENV) causes the most prevalent arthropod-borne viral disease worldwide. While its incidence is increasing in many countries, there is no approved antiviral therapy currently available. In infected cells, the DENV induces extensive morphological alterations of the endoplasmic reticulum (ER) to [...] Read more.

The dengue virus (DENV) causes the most prevalent arthropod-borne viral disease worldwide. While its incidence is increasing in many countries, there is no approved antiviral therapy currently available. In infected cells, the DENV induces extensive morphological alterations of the endoplasmic reticulum (ER) to generate viral replication organelles (vRO), which include convoluted membranes (CM) and vesicle packets (VP) hosting viral RNA replication. The viral non-structural protein NS4B localizes to vROs and is absolutely required for viral replication through poorly defined mechanisms, which might involve cellular protein partners. Previous interactomic studies identified the ATPase valosin-containing protein (VCP) as a DENV NS4B-interacting host factor in infected cells. Using both pharmacological and dominant-negative inhibition approaches, we show, in this study, that VCP ATPase activity is required for efficient DENV replication. VCP associates with NS4B when expressed in the absence of other viral proteins while in infected cells, both proteins colocalize within large DENV-induced cytoplasmic structures previously demonstrated to be CMs. Consistently, VCP inhibition dramatically reduces the abundance of DENV CMs in infected cells. Most importantly, using a recently reported replication-independent plasmid-based vRO induction system, we show that de novo VP biogenesis is dependent on VCP ATPase activity. Overall, our data demonstrate that VCP ATPase activity is required for vRO morphogenesis and/or stability. Considering that VCP was shown to be required for the replication of other flaviviruses, our results argue that VCP is a pan-flaviviral host dependency factor. Given that new generation VCP-targeting drugs are currently evaluated in clinical trials for cancer treatment, VCP may constitute an attractive broad-spectrum antiviral target in drug repurposing approaches. Full article

(This article belongs to the Special Issue Chaperones and Viral-Host Interactions)

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15 pages, 1251 KiB

Open AccessReview

The Potential Role of COVID-19 in the Pathogenesis of Multiple Sclerosis—A Preliminary Report

by Noothan J. Satheesh, Salam Salloum-Asfar and Sara A. Abdulla

Viruses 2021, 13(10), 2091; https://doi.org/10.3390/v13102091 - 17 Oct 2021

Cited by 16 | Viewed by 4877

Abstract

Coronavirus 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the lungs. COVID-19 symptoms include the presence of fevers, dry coughs, fatigue, sore throat, headaches, diarrhea, and a loss of taste or smell. [...] Read more.

Coronavirus 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the lungs. COVID-19 symptoms include the presence of fevers, dry coughs, fatigue, sore throat, headaches, diarrhea, and a loss of taste or smell. However, it is understood that SARS-CoV-2 is neurotoxic and neuro-invasive and could enter the central nervous system (CNS) via the hematogenous route or via the peripheral nerve route and causes encephalitis, encephalopathy, and acute disseminated encephalomyelitis (ADEM) in COVID-19 patients. This review discusses the possibility of SARS-CoV-2-mediated Multiple Sclerosis (MS) development in the future, comparable to the surge in Parkinson’s disease cases following the Spanish Flu in 1918. Moreover, the SARS-CoV-2 infection is associated with a cytokine storm. This review highlights the impact of these modulated cytokines on glial cell interactions within the CNS and their role in potentially prompting MS development as a secondary disease by SARS-CoV-2. SARS-CoV-2 is neurotropic and could interfere with various functions of neurons leading to MS development. The influence of neuroinflammation, microglia phagocytotic capabilities, as well as hypoxia-mediated mitochondrial dysfunction and neurodegeneration, are mechanisms that may ultimately trigger MS development. Full article

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

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13 pages, 874 KiB

Open AccessReview

Innate Immune Responses to Influenza Virus Infections in the Upper Respiratory Tract

by Edin J. Mifsud, Miku Kuba and Ian G. Barr

Viruses 2021, 13(10), 2090; https://doi.org/10.3390/v13102090 - 17 Oct 2021

Cited by 45 | Viewed by 11480

Abstract

The innate immune system is the host’s first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must replicate in epithelial cells of the upper respiratory tract. However, there are several innate immune [...] Read more.

The innate immune system is the host’s first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must replicate in epithelial cells of the upper respiratory tract. However, there are several innate immune mechanisms in place to stop the virus from reaching epithelial cells. In addition to limiting viral replication and dissemination, the innate immune system also activates the adaptive immune system leading to viral clearance, enabling the respiratory system to return to normal homeostasis. However, an overzealous innate immune system or adaptive immune response can be associated with immunopathology and aid secondary bacterial infections of the lower respiratory tract leading to pneumonia. In this review, we discuss the mechanisms utilised by the innate immune system to limit influenza virus replication and the damage caused by influenza viruses on the respiratory tissues and how these very same protective immune responses can cause immunopathology. Full article

(This article belongs to the Special Issue Immunity to Influenza Viruses)

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7 pages, 506 KiB

Open AccessCommunication

Viral Shedding among Re-Positive Severe Acute Respiratory Syndrome Coronavirus-2 Positive Individuals in Republic of Korea

by Jeong-Min Kim, Boyeong Ryu, Young June Choe, Hye-Jun Jo, Hyeokjin Lee, Heui Man Kim, Nam-Joo Lee, Jee Eun Rhee, Yoon-Seok Chung, Myung-Guk Han, Eun-Jin Kim, Youngjoon Park, Jin Gwack, Yeowon Jin, Jeongsuk Song, Seunghee Seo, Byoungchul Gill, Hyunyeong Kim, Yeeun Park, Cheon Kwon Yoo and Eun Kyeong Jeong Show full author list Hide full author list

Viruses 2021, 13(10), 2089; https://doi.org/10.3390/v13102089 - 17 Oct 2021

Cited by 4 | Viewed by 4934

Abstract

This study investigated the infectivity of severe acute respiratory syndrome (SARS-CoV-2) in individuals who re-tested positive for SARS-CoV-2 RNA after recovering from their primary illness. We investigated 295 individuals with re-positive SARS-CoV-2 polymerase chain reaction (PCR) test results and 836 of their close [...] Read more.

This study investigated the infectivity of severe acute respiratory syndrome (SARS-CoV-2) in individuals who re-tested positive for SARS-CoV-2 RNA after recovering from their primary illness. We investigated 295 individuals with re-positive SARS-CoV-2 polymerase chain reaction (PCR) test results and 836 of their close contacts. We attempted virus isolation in individuals with re-positive SARS-CoV-2 PCR test results using cell culture and confirmed the presence of neutralizing antibodies using serological tests. Viral culture was negative in all 108 individuals with re-positive SARS-CoV-2 PCR test results in whom viral culture was performed. Three new cases of SARS-CoV-2 infection were identified among household contacts using PCR. Two of the three new cases had had contact with the index patient during their primary illness, and all three had antibody evidence of past infection. Thus, there was no laboratory evidence of viral shedding and no epidemiological evidence of transmission among individuals with re-positive SARS-CoV-2 PCR test results. Full article

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

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11 pages, 4515 KiB

Open AccessReview

Nonhuman Primate Models of Zika Virus Infection and Disease during Pregnancy

by Nicole N. Haese, Victoria H. J. Roberts, Athena Chen, Daniel N. Streblow, Terry K. Morgan and Alec J. Hirsch

Viruses 2021, 13(10), 2088; https://doi.org/10.3390/v13102088 - 16 Oct 2021

Cited by 17 | Viewed by 3328

Abstract

Since the explosive outbreak of Zika virus in Brazil and South/Central America in 2015–2016, the frequency of infections has subsided, but Zika virus remains present in this region as well as other tropical and sub-tropical areas of the globe. The most alarming aspect [...] Read more.

Since the explosive outbreak of Zika virus in Brazil and South/Central America in 2015–2016, the frequency of infections has subsided, but Zika virus remains present in this region as well as other tropical and sub-tropical areas of the globe. The most alarming aspect of Zika virus infection is its association with severe birth defects when infection occurs in pregnant women. Understanding the mechanism of Zika virus pathogenesis, which comprises features unique to Zika virus as well as shared with other teratogenic pathogens, is key to future prophylactic or therapeutic interventions. Nonhuman primate-based research has played a significant role in advancing our knowledge of Zika virus pathogenesis, especially with regard to fetal infection. This review summarizes what we have learned from these models and potential future research directions. Full article

(This article belongs to the Special Issue Cell, Organoid and Animal Models to Study Pathogenic Human RNA Viruses)

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18 pages, 3112 KiB

Open AccessArticle

Identification and Characterization of Swine Influenza Virus H1N1 Variants Generated in Vaccinated and Nonvaccinated, Challenged Pigs

by Álvaro López-Valiñas, Marta Sisteré-Oró, Sergi López-Serrano, Laura Baioni, Ayub Darji, Chiara Chiapponi, Joaquim Segalés, Llilianne Ganges and José I. Núñez

Viruses 2021, 13(10), 2087; https://doi.org/10.3390/v13102087 - 16 Oct 2021

Cited by 9 | Viewed by 3723

Abstract

Influenza viruses represent a continuous threat to both animal and human health. The 2009 H1N1 A influenza pandemic highlighted the importance of a swine host in the adaptation of influenza viruses to humans. Nowadays, one of the most extended strategies used to control [...] Read more.

Influenza viruses represent a continuous threat to both animal and human health. The 2009 H1N1 A influenza pandemic highlighted the importance of a swine host in the adaptation of influenza viruses to humans. Nowadays, one of the most extended strategies used to control swine influenza viruses (SIVs) is the trivalent vaccine application, whose formulation contains the most frequently circulating SIV subtypes H1N1, H1N2, and H3N2. These vaccines do not provide full protection against the virus, allowing its replication, evolution, and adaptation. To better understand the main mechanisms that shape viral evolution, here, the SIV intra-host diversity was analyzed in samples collected from both vaccinated and nonvaccinated animals challenged with the H1N1 influenza A virus. Twenty-eight whole SIV genomes were obtained by next-generation sequencing, and differences in nucleotide variants between groups were established. Substitutions were allocated along all influenza genetic segments, while the most relevant nonsynonymous substitutions were allocated in the NS1 protein on samples collected from vaccinated animals, suggesting that SIV is continuously evolving despite vaccine application. Moreover, new viral variants were found in both vaccinated and nonvaccinated pigs, showing relevant substitutions in the HA, NA, and NP proteins, which may increase viral fitness under field conditions. Full article

(This article belongs to the Special Issue Endemic and Emerging Swine Viruses 2021)

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11 pages, 1409 KiB

Open AccessArticle

Evolutionary Dynamics of H5 Highly Pathogenic Avian Influenza Viruses (Clade 2.3.4.4B) Circulating in Bulgaria in 2019–2021

by Bianca Zecchin, Gabriela Goujgoulova, Isabella Monne, Annalisa Salviato, Alessia Schivo, Iskra Slavcheva, Ambra Pastori, Ian H. Brown, Nicola S. Lewis, Calogero Terregino and Alice Fusaro

Viruses 2021, 13(10), 2086; https://doi.org/10.3390/v13102086 - 16 Oct 2021

Cited by 11 | Viewed by 3372

Abstract

The first detection of a Highly Pathogenic Avian Influenza (HPAI) H5N8 virus in Bulgaria dates back to December 2016. Since then, many outbreaks caused by HPAI H5 viruses from clade 2.3.4.4B have been reported in both domestic and wild birds in different regions [...] Read more.

The first detection of a Highly Pathogenic Avian Influenza (HPAI) H5N8 virus in Bulgaria dates back to December 2016. Since then, many outbreaks caused by HPAI H5 viruses from clade 2.3.4.4B have been reported in both domestic and wild birds in different regions of the country. In this study, we characterized the complete genome of sixteen H5 viruses collected in Bulgaria between 2019 and 2021. Phylogenetic analyses revealed a persistent circulation of the H5N8 strain for four consecutive years (December 2016–June 2020) and the emergence in 2020 of a novel reassortant H5N2 subtype, likely in a duck farm. Estimation of the time to the most recent common ancestor indicates that this reassortment event may have occurred between May 2019 and January 2020. At the beginning of 2021, Bulgaria experienced a new virus introduction in the poultry sector, namely a HPAI H5N8 that had been circulating in Europe since October 2020. The periodical identification in domestic birds of H5 viruses related to the 2016 epidemic as well as a reassortant strain might indicate undetected circulation of the virus in resident wild birds or in the poultry sector. To avoid the concealed circulation and evolution of viruses, and the risk of emergence of strains with pandemic potential, the implementation of control measures is of utmost importance, particularly in duck farms where birds display no clinical signs. Full article

(This article belongs to the Special Issue Drivers of Evolution of Animal RNA Viruses)

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22 pages, 7086 KiB

Open AccessArticle

Towards a Precision Medicine Approach and In Situ Vaccination against Prostate Cancer by PSMA-Retargeted oHSV

by Andrea Vannini, Federico Parenti, Daniela Bressanin, Catia Barboni, Anna Zaghini, Gabriella Campadelli-Fiume and Tatiana Gianni

Viruses 2021, 13(10), 2085; https://doi.org/10.3390/v13102085 - 16 Oct 2021

Cited by 3 | Viewed by 2643

Abstract

Prostate specific membrane antigen (PSMA) is a specific high frequency cell surface marker of prostate cancers. Theranostic approaches targeting PSMA show no major adverse effects and rule out off-tumor toxicity. A PSMA-retargeted oHSV (R-405) was generated which both infected and was cytotoxic exclusively [...] Read more.

Prostate specific membrane antigen (PSMA) is a specific high frequency cell surface marker of prostate cancers. Theranostic approaches targeting PSMA show no major adverse effects and rule out off-tumor toxicity. A PSMA-retargeted oHSV (R-405) was generated which both infected and was cytotoxic exclusively for PSMA-positive cells, including human prostate cancer LNCaP and 22Rv1 cells, and spared PSMA-negative cells. R-405 in vivo efficacy against LLC1-PSMA and Renca-PSMA tumors consisted of inhibiting primary tumor growth, establishing long-term T immune response, immune heating of the microenvironment, de-repression of the anti-tumor immune phenotype, and sensitization to checkpoint blockade. The in situ vaccination protected from distant challenge tumors, both PSMA-positive and PSMA-negative, implying that it was addressed also to LLC1 tumor antigens. PSMA-retargeted oHSVs are a precision medicine tool worth being additionally investigated in the immunotherapeutic and in situ vaccination landscape against prostate cancers. Full article

(This article belongs to the Special Issue Oncolytic HSVs)

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18 pages, 35740 KiB

Open AccessArticle

Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARS-CoV-2- Positive Patients

by Valeria Inés Segatori, Juan Garona, Lorena Grisel Caligiuri, Juan Bizzotto, Rosario Lavignolle, Ayelén Toro, Pablo Sanchis, Eduardo Spitzer, Alejandro Krolewiecki, Geraldine Gueron and Daniel Fernando Alonso

Viruses 2021, 13(10), 2084; https://doi.org/10.3390/v13102084 - 15 Oct 2021

Cited by 8 | Viewed by 7444

Abstract

Nuclear transport and vesicle trafficking are key cellular functions involved in the pathogenesis of RNA viruses. Among other pleiotropic effects on virus-infected host cells, ivermectin (IVM) inhibits nuclear transport mechanisms mediated by importins and atorvastatin (ATV) affects actin cytoskeleton-dependent trafficking controlled by Rho [...] Read more.

Nuclear transport and vesicle trafficking are key cellular functions involved in the pathogenesis of RNA viruses. Among other pleiotropic effects on virus-infected host cells, ivermectin (IVM) inhibits nuclear transport mechanisms mediated by importins and atorvastatin (ATV) affects actin cytoskeleton-dependent trafficking controlled by Rho GTPases signaling. In this work, we first analyzed the response to infection in nasopharyngeal swabs from SARS-CoV-2-positive and -negative patients by assessing the gene expression of the respective host cell drug targets importins and Rho GTPases. COVID-19 patients showed alterations in KPNA3, KPNA5, KPNA7, KPNB1, RHOA, and CDC42 expression compared with non-COVID-19 patients. An in vitro model of infection with Poly(I:C), a synthetic analog of viral double-stranded RNA, triggered NF-κB activation, an effect that was halted by IVM and ATV treatment. Importin and Rho GTPases gene expression was also impaired by these drugs. Furthermore, through confocal microscopy, we analyzed the effects of IVM and ATV on nuclear to cytoplasmic importin α distribution, alone or in combination. Results showed a significant inhibition of importin α nuclear accumulation under IVM and ATV treatments. These findings confirm transcriptional alterations in importins and Rho GTPases upon SARS-CoV-2 infection and point to IVM and ATV as valid drugs to impair nuclear localization of importin α when used at clinically-relevant concentrations. Full article

(This article belongs to the Special Issue Towards Host-Centric Antivirals)

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Graphical abstract

25 pages, 3694 KiB

Open AccessArticle

Molecular Characterization and Taxonomic Assignment of Three Phage Isolates from a Collection Infecting Pseudomonas syringae pv. actinidiae and P. syringae pv. phaseolicola from Northern Italy

by Gabriele Martino, Dominique Holtappels, Marta Vallino, Marco Chiapello, Massimo Turina, Rob Lavigne, Jeroen Wagemans and Marina Ciuffo

Viruses 2021, 13(10), 2083; https://doi.org/10.3390/v13102083 - 15 Oct 2021

Cited by 12 | Viewed by 3733

Abstract

Bacterial kiwifruit vine disease (Pseudomonas syringae pv. actinidiae, Psa) and halo blight of bean (P. syringae pv. phaseolicola, Pph) are routinely treated with copper, leading to environmental pollution and bacterial copper resistance. An alternative sustainable control method could [...] Read more.

Bacterial kiwifruit vine disease (Pseudomonas syringae pv. actinidiae, Psa) and halo blight of bean (P. syringae pv. phaseolicola, Pph) are routinely treated with copper, leading to environmental pollution and bacterial copper resistance. An alternative sustainable control method could be based on bacteriophages, as phage biocontrol offers high specificity and does not result in the spread of toxic residues into the environment or the food chain. In this research, specific phages suitable for phage-based biocontrol strategies effective against Psa and Pph were isolated and characterized. In total, sixteen lytic Pph phage isolates and seven lytic Psa phage isolates were isolated from soil in Piedmont and Veneto in northern Italy. Genome characterization of fifteen selected phages revealed that the isolated Pph phages were highly similar and could be considered as isolates of a novel species, whereas the isolated Psa phages grouped into four distinct clades, two of which represent putative novel species. No lysogeny-, virulence- or toxin-related genes were found in four phages, making them suitable for potential biocontrol purposes. A partial biological characterization including a host range analysis was performed on a representative subset of these isolates. This analysis was a prerequisite to assess their efficacy in greenhouse and in field trials, using different delivery strategies. Full article

(This article belongs to the Special Issue Bacteriophage-Based Biocontrol in Agriculture)

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11 pages, 16352 KiB

Open AccessBrief Report

Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro

by Yuyong Zhou, Karen A. Gammeltoft, Andrea Galli, Anna Offersgaard, Ulrik Fahnøe, Santseharay Ramirez, Jens Bukh and Judith M. Gottwein

Viruses 2021, 13(10), 2082; https://doi.org/10.3390/v13102082 - 15 Oct 2021

Cited by 23 | Viewed by 4026

Abstract

We report the in vitro efficacy of ion-channel inhibitors amantadine, memantine and rimantadine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In VeroE6 cells, rimantadine was most potent followed by memantine and amantadine (50% effective concentrations: 36, 80 and 116 µM, respectively). Rimantadine [...] Read more.

We report the in vitro efficacy of ion-channel inhibitors amantadine, memantine and rimantadine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In VeroE6 cells, rimantadine was most potent followed by memantine and amantadine (50% effective concentrations: 36, 80 and 116 µM, respectively). Rimantadine also showed the highest selectivity index, followed by amantadine and memantine (17.3, 12.2 and 7.6, respectively). Similar results were observed in human hepatoma Huh7.5 and lung carcinoma A549-hACE2 cells. Inhibitors interacted in a similar antagonistic manner with remdesivir and had a similar barrier to viral escape. Rimantadine acted mainly at the viral post-entry level and partially at the viral entry level. Based on these results, rimantadine showed the most promise for treatment of SARS-CoV-2. Full article

(This article belongs to the Collection Coronaviruses)

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9 pages, 1467 KiB

Open AccessCommunication

Transmission of Grapevine leafroll-associated virus-1 (Ampelovirus) and Grapevine virus A (Vitivirus) by the Cottony Grape Scale, Pulvinaria vitis (Hemiptera: Coccidae)

by Gérard Hommay, Antoine Alliaume, Catherine Reinbold and Etienne Herrbach

Viruses 2021, 13(10), 2081; https://doi.org/10.3390/v13102081 - 15 Oct 2021

Cited by 5 | Viewed by 2393

Abstract

The cottony grape scale Pulvinaria vitis is a scale insect colonizing grapevine; however, its capacity as a vector of grapevine viruses is poorly known in comparison to other scale species that are vectors of viral species in the genera Ampelovirus and Vitivirus. [...] Read more.

The cottony grape scale Pulvinaria vitis is a scale insect colonizing grapevine; however, its capacity as a vector of grapevine viruses is poorly known in comparison to other scale species that are vectors of viral species in the genera Ampelovirus and Vitivirus. The ability of P. vitis to transmit the ampeloviruses Grapevine leafroll-associated viruses [GLRaV]−1, −3, and −4, and the vitivirus Grapevine virus A (GVA), to healthy vine cuttings was assessed. The scale insects used originated from commercial vine plots located in Alsace, Eastern France. When nymphs sampled from leafroll-infected vineyard plants were transferred onto healthy cuttings, only one event of transmission was obtained. However, when laboratory-reared, non-viruliferous nymphs were allowed to acquire viruses under controlled conditions, both first and second instar nymphs derived from two vineyards were able to transmit GLRaV−1 and GVA. This is the first report of GLRaV−1 and GVA transmission from grapevine to grapevine by this species. Full article

(This article belongs to the Special Issue Closteroviridae)

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13 pages, 1046 KiB

Open AccessArticle

Comparison of Eight Commercially Available Faecal Point-of-Care Tests for Detection of Canine Parvovirus Antigen

by Julia Walter-Weingärtner, Michèle Bergmann, Karin Weber, Uwe Truyen, Cosmin Muresan and Katrin Hartmann

Viruses 2021, 13(10), 2080; https://doi.org/10.3390/v13102080 - 15 Oct 2021

Cited by 7 | Viewed by 4271

Abstract

A real-time polymerase chain reaction (qPCR) is considered the gold standard for the laboratory diagnosis of canine parvovirus (CPV) infection but can only be performed in specialized laboratories. Several point-of-care tests (POCT), detecting CPV antigens in faeces within minutes, are commercially available. The [...] Read more.

A real-time polymerase chain reaction (qPCR) is considered the gold standard for the laboratory diagnosis of canine parvovirus (CPV) infection but can only be performed in specialized laboratories. Several point-of-care tests (POCT), detecting CPV antigens in faeces within minutes, are commercially available. The aim of this study was to evaluate eight POCT in comparison with qPCR. Faecal samples of 150 dogs from three groups (H: 50 client-owned, healthy dogs, not vaccinated within the last four weeks; S: 50 shelter dogs, healthy, not vaccinated within the last four weeks; p = 50 dogs with clinical signs of CPV infection) were tested with eight POCT and qPCR. Practicability, sensitivity, specificity, positive (PPV) and negative predictive values (NPV), as well as overall accuracy were determined. To assess the differences between and agreement among POCT, McNemar’s test and Cohen’s Kappa statistic were performed. Specificity and PPV were 100.0% in all POCT. Sensitivity varied from 22.9–34.3% overall and from 32.7–49.0% in group P. VetexpertRapidTestCPVAg^® had the highest sensitivity (34.3% overall, 49.0% group P) and differed significantly from the 3 POCT with the lowest sensitivities (Fassisi^®Parvo (27.7% overall, 36.7% group P), Primagnost^®ParvoH+K (24.3% overall, 34.7% group P), FASTest^®PARVOCard (22.9% overall, 32.7% group P)). The agreement among all POCT was at least substantial (kappa >0.80). A positive POCT result confirmed the infection with CPV in unvaccinated dogs, whereas a negative POCT result did not definitely exclude CPV infection due to the low sensitivity of all POCT. Full article

(This article belongs to the Special Issue Enteric and Respiratory Viruses in Animals)

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21 pages, 3052 KiB

Open AccessArticle

The Expression Level of HIV-1 Vif Is Optimized by Nucleotide Changes in the Genomic SA1D2prox Region during the Viral Adaptation Process

by Takaaki Koma, Naoya Doi, Mai Takemoto, Kyosuke Watanabe, Hideki Yamamoto, Satoshi Nakashima, Akio Adachi and Masako Nomaguchi

Viruses 2021, 13(10), 2079; https://doi.org/10.3390/v13102079 - 15 Oct 2021

Cited by 2 | Viewed by 2369

Abstract

HIV-1 Vif plays an essential role in viral replication by antagonizing anti-viral cellular restriction factors, a family of APOBEC3 proteins. We have previously shown that naturally-occurring single-nucleotide mutations in the SA1D2prox region, which surrounds the splicing acceptor 1 and splicing donor 2 sites [...] Read more.

HIV-1 Vif plays an essential role in viral replication by antagonizing anti-viral cellular restriction factors, a family of APOBEC3 proteins. We have previously shown that naturally-occurring single-nucleotide mutations in the SA1D2prox region, which surrounds the splicing acceptor 1 and splicing donor 2 sites of the HIV-1 genome, dramatically alter the Vif expression level, resulting in variants with low or excessive Vif expression. In this study, we investigated how these HIV-1 variants with poor replication ability adapt and evolve under the pressure of APOBEC3 proteins. Adapted clones obtained through adaptation experiments exhibited an altered replication ability and Vif expression level compared to each parental clone. While various mutations were present throughout the viral genome, all replication-competent adapted clones with altered Vif expression levels were found to bear them within SA1D2prox, without exception. Indeed, the mutations identified within SA1D2prox were responsible for changes in the Vif expression levels and altered the splicing pattern. Moreover, for samples collected from HIV-1-infected patients, we showed that the nucleotide sequences of SA1D2prox can be chronologically changed and concomitantly affect the Vif expression levels. Taken together, these results demonstrated the importance of the SA1D2prox nucleotide sequence for modulating the Vif expression level during HIV-1 replication and adaptation. Full article

(This article belongs to the Special Issue RNA Viruses: Structure, Adaptation, and Evolution)

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24 pages, 5556 KiB

Open AccessReview

Clonal Expansion of Infected CD4+ T Cells in People Living with HIV

by John M. Coffin and Stephen H. Hughes

Viruses 2021, 13(10), 2078; https://doi.org/10.3390/v13102078 - 15 Oct 2021

Cited by 12 | Viewed by 3821

Abstract

HIV infection is not curable with current antiretroviral therapy (ART) because a small fraction of CD4+ T cells infected prior to ART initiation persists. Understanding the nature of this latent reservoir and how it is created is essential to development of potentially curative [...] Read more.

HIV infection is not curable with current antiretroviral therapy (ART) because a small fraction of CD4+ T cells infected prior to ART initiation persists. Understanding the nature of this latent reservoir and how it is created is essential to development of potentially curative strategies. The discovery that a large fraction of the persistently infected cells in individuals on suppressive ART are members of large clones greatly changed our view of the reservoir and how it arises. Rather than being the products of infection of resting cells, as was once thought, HIV persistence is largely or entirely a consequence of infection of cells that are either expanding or are destined to expand, primarily due to antigen-driven activation. Although most of the clones carry defective proviruses, some carry intact infectious proviruses; these clones comprise the majority of the reservoir. A large majority of both the defective and the intact infectious proviruses in clones of infected cells are transcriptionally silent; however, a small fraction expresses a few copies of unspliced HIV RNA. A much smaller fraction is responsible for production of low levels of infectious virus, which can rekindle infection when ART is stopped. Further understanding of the reservoir will be needed to clarify the mechanism(s) by which provirus expression is controlled in the clones of cells that constitute the reservoir. Full article

(This article belongs to the Special Issue Mechanisms of Viral Persistence)

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19 pages, 1776 KiB

Open AccessReview

Roles of Non-Structural Protein 4A in Flavivirus Infection

by Paeka Klaitong and Duncan R. Smith

Viruses 2021, 13(10), 2077; https://doi.org/10.3390/v13102077 - 15 Oct 2021

Cited by 27 | Viewed by 3777

Abstract

Infections with viruses in the genus Flavivirus are a worldwide public health problem. These enveloped, positive sense single stranded RNA viruses use a small complement of only 10 encoded proteins and the RNA genome itself to remodel host cells to achieve conditions favoring [...] Read more.

Infections with viruses in the genus Flavivirus are a worldwide public health problem. These enveloped, positive sense single stranded RNA viruses use a small complement of only 10 encoded proteins and the RNA genome itself to remodel host cells to achieve conditions favoring viral replication. A consequence of the limited viral armamentarium is that each protein exerts multiple cellular effects, in addition to any direct role in viral replication. The viruses encode four non-structural (NS) small transmembrane proteins (NS2A, NS2B, NS4A and NS4B) which collectively remain rather poorly characterized. NS4A is a 16kDa membrane associated protein and recent studies have shown that this protein plays multiple roles, including in membrane remodeling, antagonism of the host cell interferon response, and in the induction of autophagy, in addition to playing a role in viral replication. Perhaps most importantly, NS4A has been implicated as playing a critical role in fetal developmental defects seen as a consequence of Zika virus infection during pregnancy. This review provides a comprehensive overview of the multiple roles of this small but pivotal protein in mediating the pathobiology of flaviviral infections. Full article

(This article belongs to the Section Animal Viruses)

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