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Viruses, Volume 14, Issue 1 (January 2022) – 165 articles

Cover Story (view full-size image): Omicron, the most recent SARS-CoV-2 variant of concern, harbors multiple mutations in the spike protein. Initial studies suggest that Omicron substantially reduces the neutralizing capability of antibodies induced from COVID-19 vaccination or previous infection. However, its effect on T cells remains to be determined. This work assesses the effect of Omicron mutations on T cell epitopes known to be targeted in COVID-19-infected or -vaccinated individuals. It is shown that 80% of epitopes within the spike protein and 97% of epitopes outside the spike protein are unaffected by Omicron mutations. Moreover, among the small fraction of epitopes comprising Omicron mutations, the majority are still predicted to be presented to T cells. Thus, T cell responses induced by previous infection or vaccination will likely remain intact and continue to provide protection against severe disease. View this paper.
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19 pages, 4938 KiB  
Article
Reduced Replication of Highly Pathogenic Avian Influenza Virus in Duck Endothelial Cells Compared to Chicken Endothelial Cells Is Associated with Stronger Antiviral Responses
by Anja C. M. de Bruin, Monique I. Spronken, Theo M. Bestebroer, Ron A. M. Fouchier and Mathilde Richard
Viruses 2022, 14(1), 165; https://doi.org/10.3390/v14010165 - 17 Jan 2022
Cited by 11 | Viewed by 3315
Abstract
Highly pathogenic avian influenza viruses (HPAIVs) cause fatal systemic infections in chickens, which are associated with endotheliotropism. HPAIV infections in wild birds are generally milder and not endotheliotropic. Here, we aimed to elucidate the species-specific endotheliotropism of HPAIVs using primary chicken and duck [...] Read more.
Highly pathogenic avian influenza viruses (HPAIVs) cause fatal systemic infections in chickens, which are associated with endotheliotropism. HPAIV infections in wild birds are generally milder and not endotheliotropic. Here, we aimed to elucidate the species-specific endotheliotropism of HPAIVs using primary chicken and duck aortic endothelial cells (chAEC and dAEC respectively). Viral replication kinetics and host responses were assessed in chAEC and dAEC upon inoculation with HPAIV H5N1 and compared to embryonic fibroblasts. Although dAEC were susceptible to HPAIV upon inoculation at high multiplicity of infection, HPAIV replicated to lower levels in dAEC than chAEC during multi-cycle replication. The susceptibility of duck embryonic endothelial cells to HPAIV was confirmed in embryos. Innate immune responses upon HPAIV inoculation differed between chAEC, dAEC, and embryonic fibroblasts. Expression of the pro-inflammatory cytokine IL8 increased in chicken cells but decreased in dAEC. Contrastingly, the induction of antiviral responses was stronger in dAEC than in chAEC, and chicken and duck fibroblasts. Taken together, these data demonstrate that although duck endothelial cells are permissive to HPAIV infection, they display markedly different innate immune responses than chAEC and embryonic fibroblasts. These differences may contribute to the species-dependent differences in endotheliotropism and consequently HPAIV pathogenesis. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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29 pages, 955 KiB  
Review
Immune Profiling of COVID-19 in Correlation with SARS and MERS
by Bariaa A. Khalil, Sarra B. Shakartalla, Swati Goel, Bushra Madkhana, Rabih Halwani, Azzam A. Maghazachi, Habiba AlSafar, Basem Al-Omari and Mohammad T. Al Bataineh
Viruses 2022, 14(1), 164; https://doi.org/10.3390/v14010164 - 17 Jan 2022
Cited by 10 | Viewed by 3768
Abstract
Acute respiratory distress syndrome (ARDS) is a major complication of the respiratory illness coronavirus disease 2019, with a death rate reaching up to 40%. The main underlying cause of ARDS is a cytokine storm that results in a dysregulated immune response. This review [...] Read more.
Acute respiratory distress syndrome (ARDS) is a major complication of the respiratory illness coronavirus disease 2019, with a death rate reaching up to 40%. The main underlying cause of ARDS is a cytokine storm that results in a dysregulated immune response. This review discusses the role of cytokines and chemokines in SARS-CoV-2 and its predecessors SARS-CoV and MERS-CoV, with particular emphasis on the elevated levels of inflammatory mediators that are shown to be correlated with disease severity. For this purpose, we reviewed and analyzed clinical studies, research articles, and reviews published on PubMed, EMBASE, and Web of Science. This review illustrates the role of the innate and adaptive immune responses in SARS, MERS, and COVID-19 and identifies the general cytokine and chemokine profile in each of the three infections, focusing on the most prominent inflammatory mediators primarily responsible for the COVID-19 pathogenesis. The current treatment protocols or medications in clinical trials were reviewed while focusing on those targeting cytokines and chemokines. Altogether, the identified cytokines and chemokines profiles in SARS-CoV, MERS-CoV, and SARS-CoV-2 provide important information to better understand SARS-CoV-2 pathogenesis and highlight the importance of using prominent inflammatory mediators as markers for disease diagnosis and management. Our findings recommend that the use of immunosuppression cocktails provided to patients should be closely monitored and continuously assessed to maintain the desirable effects of cytokines and chemokines needed to fight the SARS, MERS, and COVID-19. The current gap in evidence is the lack of large clinical trials to determine the optimal and effective dosage and timing for a therapeutic regimen. Full article
(This article belongs to the Section SARS-CoV-2 and COVID-19)
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6 pages, 216 KiB  
Communication
Real-Life Impact of Drug Toxicity on Dolutegravir Tolerability: Clinical Practice Data from a Multicenter Italian Cohort
by Arturo Ciccullo, Gianmaria Baldin, Vanni Borghi, Filippo Lagi, Alessandra Latini, Gabriella d’Ettorre, Letizia Oreni, Paolo Fusco, Amedeo Capetti, Massimiliano Fabbiani, Andrea Giacomelli, Alessandro Grimaldi, Giordano Madeddu, Gaetana Sterrantino, Cristina Mussini and Simona Di Giambenedetto
Viruses 2022, 14(1), 163; https://doi.org/10.3390/v14010163 - 17 Jan 2022
Cited by 6 | Viewed by 1877
Abstract
Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We [...] Read more.
Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We enrolled 3775 PLWHIV: 2763 (73.2%) were males, with a median age of 50 years. During 9890.7 PYFU, we observed 930 discontinuations (9.4 per 100 PYFU). Estimated probabilities of maintaining DTG at three and five years were 75.1% and 67.2%, respectively. Treatment-naïve pts showed a lower probability of maintaining DTG at three and five years compared to treatment-experienced PLWHIV (log-rank p < 0.001). At a multivariate analysis, a longer time of virological suppression (aHR 0.994, p < 0.001) and having experienced a previous virological failure (aHR 0.788, p = 0.016) resulted protective against DTG discontinuation. Most discontinuations (84.0%) happened within the first 12 months of DTG initiation, in particular, 92.2% of discontinuations due to neuropsychiatric toxicity were observed in the first year. Our data confirm the overall good tolerability of DTG in clinical practice, with a low rate of discontinuations. CNS toxicity resulted the main reason for DTG discontinuation, with most related interruptions happening in the first year from DTG introduction. Full article
(This article belongs to the Special Issue Adverse Effects of Antiretroviral Therapy)
18 pages, 3443 KiB  
Article
Novel Epidemic Metrics to Communicate Outbreak Risk at the Municipality Level: Dengue and Zika in the Dominican Republic
by Rhys Kingston, Isobel Routledge, Samir Bhatt and Leigh R Bowman
Viruses 2022, 14(1), 162; https://doi.org/10.3390/v14010162 - 17 Jan 2022
Cited by 4 | Viewed by 2753
Abstract
Arboviruses remain a significant cause of morbidity, mortality and economic cost across the global human population. Epidemics of arboviral disease, such as Zika and dengue, also cause significant disruption to health services at local and national levels. This study examined 2014–2016 Zika and [...] Read more.
Arboviruses remain a significant cause of morbidity, mortality and economic cost across the global human population. Epidemics of arboviral disease, such as Zika and dengue, also cause significant disruption to health services at local and national levels. This study examined 2014–2016 Zika and dengue epidemic data at the sub-national level to characterise transmission across the Dominican Republic. For each municipality, spatio-temporal mapping was used to characterise disease burden, while data were age and sex standardised to quantify burden distributions among the population. In separate analyses, time-ordered data were combined with the underlying disease migration interval distribution to produce a network of likely transmission chain events, displayed using transmission chain likelihood matrices. Finally, municipal-specific reproduction numbers (Rm) were established using a Wallinga–Teunis matrix. Dengue and Zika epidemics peaked during weeks 39–52 of 2015 and weeks 14–27 of 2016, respectively. At the provincial level, dengue attack rates were high in Hermanas Mirabal and San José de Ocoa (58.1 and 49.2 cases per 10,000 population, respectively), compared with the Zika burden, which was highest in Independencia and San José de Ocoa (21.2 and 13.4 cases per 10,000 population, respectively). Across municipalities, high disease burden was observed in Cotuí (622 dengue cases per 10,000 population) and Jimani (32 Zika cases per 10,000 population). Municipal infector–infectee transmission likelihood matrices identified seven 0% likelihood transmission events throughout the dengue epidemic and two 0% likelihood transmission events during the Zika epidemic. Municipality reproduction numbers (Rm) were consistently higher, and persisted for a greater duration, during the Zika epidemic (Rm = 1.0) than during the dengue epidemic (Rm < 1.0). This research highlights the importance of disease surveillance in land border municipalities as an early warning for infectious disease transmission. It also demonstrates that a high number of importation events are required to sustain transmission in endemic settings, and vice versa for newly emerged diseases. The inception of a novel epidemiological metric, Rm, reports transmission risk using standardised spatial units, and can be used to identify high transmission risk municipalities to better focus public health interventions for dengue, Zika and other infectious diseases. Full article
(This article belongs to the Special Issue Mosquito-Borne Virus Ecology)
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11 pages, 1513 KiB  
Article
In the Search of Marine Pestiviruses: First Case of Phocoena Pestivirus in a Belt Sea Harbour Porpoise
by Iben Stokholm, Nicole Fischer, Christine Baechlein, Alexander Postel, Anders Galatius, Line Anker Kyhn, Charlotte Bie Thøstesen, Sara Persson, Ursula Siebert, Morten Tange Olsen and Paul Becher
Viruses 2022, 14(1), 161; https://doi.org/10.3390/v14010161 - 17 Jan 2022
Cited by 3 | Viewed by 2833
Abstract
Pestiviruses are widespread pathogens causing severe acute and chronic diseases among terrestrial mammals. Recently, Phocoena pestivirus (PhoPeV) was described in harbour porpoises (Phocoena phocoena) of the North Sea, expanding the host range to marine mammals. While the role of the virus [...] Read more.
Pestiviruses are widespread pathogens causing severe acute and chronic diseases among terrestrial mammals. Recently, Phocoena pestivirus (PhoPeV) was described in harbour porpoises (Phocoena phocoena) of the North Sea, expanding the host range to marine mammals. While the role of the virus is unknown, intrauterine infections with the most closely related pestiviruses— Bungowannah pestivirus (BuPV) and Linda virus (LindaV)—can cause increased rates of abortions and deaths in young piglets. Such diseases could severely impact already vulnerable harbour porpoise populations. Here, we investigated the presence of PhoPeV in 77 harbour porpoises, 277 harbour seals (Phoca vitulina), grey seals (Halichoerus grypus) and ringed seals (Pusa hispida) collected in the Baltic Sea region between 2002 and 2019. The full genome sequence of a pestivirus was obtained from a juvenile female porpoise collected along the coast of Zealand in Denmark in 2011. The comparative Bayesian phylogenetic analyses revealed a close relationship between the new PhoPeV sequence and previously published North Sea sequences with a recent divergence from genotype 1 sequences between 2005 and 2009. Our findings provide further insight into the circulation of PhoPeV and expand the distribution from the North Sea to the Baltic Sea region with possible implications for the vulnerable Belt Sea and endangered Baltic Proper harbour porpoise populations. Full article
(This article belongs to the Topic Veterinary Infectious Diseases)
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19 pages, 4055 KiB  
Article
Nectin-2 Acts as a Viral Entry Mediated Molecule That Binds to Human Herpesvirus 6B Glycoprotein B
by Hirohito Ogawa, Daisuke Fujikura, Hikaru Namba, Nobuko Yamashita, Tomoyuki Honda and Masao Yamada
Viruses 2022, 14(1), 160; https://doi.org/10.3390/v14010160 - 16 Jan 2022
Cited by 6 | Viewed by 2792
Abstract
Human herpesvirus 6B (HHV-6B) is a T-lymphotropic virus and the etiological agent of exanthem subitum. HHV-6B is present in a latent or persistent form after primary infection and is produced in the salivary glands or transmitted to this organ. Infected individuals continue to [...] Read more.
Human herpesvirus 6B (HHV-6B) is a T-lymphotropic virus and the etiological agent of exanthem subitum. HHV-6B is present in a latent or persistent form after primary infection and is produced in the salivary glands or transmitted to this organ. Infected individuals continue to secrete the virus in their saliva, which is thus considered a source for virus transmission. HHV-6B primarily propagates in T cells because its entry receptor, CD134, is mainly expressed by activated T cells. The virus then spreads to the host’s organs, including the salivary glands, nervous system, and liver. However, CD134 expression is not detected in these organs. Therefore, HHV-6B may be entering cells via a currently unidentified cell surface molecule, but the mechanisms for this have not yet been investigated. In this study, we investigated a CD134-independent virus entry mechanism in the parotid-derived cell line HSY. First, we confirmed viral infection in CD134-membrane unanchored HSY cells. We then determined that nectin cell adhesion molecule 2 (nectin-2) mediated virus entry and that HHV-6B-insensitive T-cells transduced with nectin-2 were transformed into virus-permissive cells. We also found that virus entry was significantly reduced in nectin-2 knockout parotid-derived cells. Furthermore, we showed that HHV-6B glycoprotein B (gB) interacted with the nectin-2 V-set domain. The results suggest that nectin-2 acts as an HHV-6B entry-mediated protein. Full article
(This article belongs to the Section Animal Viruses)
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22 pages, 6451 KiB  
Article
Modeling the Transmission of the SARS-CoV-2 Delta Variant in a Partially Vaccinated Population
by Ugo Avila-Ponce de León, Eric Avila-Vales and Kuan-lin Huang
Viruses 2022, 14(1), 158; https://doi.org/10.3390/v14010158 - 16 Jan 2022
Cited by 7 | Viewed by 3093
Abstract
In a population with ongoing vaccination, the trajectory of a pandemic is determined by how the virus spreads in unvaccinated and vaccinated individuals that exhibit distinct transmission dynamics based on different levels of natural and vaccine-induced immunity. We developed a mathematical model that [...] Read more.
In a population with ongoing vaccination, the trajectory of a pandemic is determined by how the virus spreads in unvaccinated and vaccinated individuals that exhibit distinct transmission dynamics based on different levels of natural and vaccine-induced immunity. We developed a mathematical model that considers both subpopulations and immunity parameters, including vaccination rates, vaccine effectiveness, and a gradual loss of protection. The model forecasted the spread of the SARS-CoV-2 delta variant in the US under varied transmission and vaccination rates. We further obtained the control reproduction number and conducted sensitivity analyses to determine how each parameter may affect virus transmission. Although our model has several limitations, the number of infected individuals was shown to be a magnitude greater (~10×) in the unvaccinated subpopulation compared to the vaccinated subpopulation. Our results show that a combination of strengthening vaccine-induced immunity and preventative behavioral measures like face mask-wearing and contact tracing will likely be required to deaccelerate the spread of infectious SARS-CoV-2 variants. Full article
(This article belongs to the Special Issue Mathematical Modeling of Viral Infection)
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10 pages, 399 KiB  
Article
Development and Evaluation of a Molecular Hepatitis A Virus Assay for Serum and Stool Specimens
by Robert A. Kozak, Candace Rutherford, Melissa Richard-Greenblatt, N. Y. Elizabeth Chau, Ana Cabrera, Mia Biondi, Jamie Borlang, Jaqueline Day, Carla Osiowy, Sumathi Ramachandran, Nancy Mayer, Laurel Glaser and Marek Smieja
Viruses 2022, 14(1), 159; https://doi.org/10.3390/v14010159 - 15 Jan 2022
Cited by 5 | Viewed by 2957
Abstract
Hepatitis A virus (HAV) is an emerging public health concern and there is an urgent need for ways to rapidly identify cases so that outbreaks can be managed effectively. Conventional testing for HAV relies on anti-HAV IgM seropositivity. However, studies estimate that 10–30% [...] Read more.
Hepatitis A virus (HAV) is an emerging public health concern and there is an urgent need for ways to rapidly identify cases so that outbreaks can be managed effectively. Conventional testing for HAV relies on anti-HAV IgM seropositivity. However, studies estimate that 10–30% of patients may not be diagnosed by serology. Molecular assays that can directly detect viral nucleic acids have the potential to improve diagnosis, which is key to prevent the spread of infections. In this study, we developed a real-time PCR (RT-PCR) assay to detect HAV RNA for the identification of acute HAV infection. Primers were designed to target the conserved 5′-untranslated region (5′-UTR) of HAV, and the assay was optimized on both the Qiagen Rotor-Gene and the BD MAX. We successfully detected HAV from patient serum and stool samples with moderate differences in sensitivity and specificity depending on the platform used. Our results highlight the clinical utility of using a molecular assay to detect HAV from various specimen types that can be implemented in hospitals to assist with diagnostics, treatment and prevention. Full article
(This article belongs to the Special Issue Recent Progress in Hepatitis A Virus Research)
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18 pages, 5159 KiB  
Article
Bayesian Inference of State-Level COVID-19 Basic Reproduction Numbers across the United States
by Abhishek Mallela, Jacob Neumann, Ely F. Miller, Ye Chen, Richard G. Posner, Yen Ting Lin and William S. Hlavacek
Viruses 2022, 14(1), 157; https://doi.org/10.3390/v14010157 - 15 Jan 2022
Cited by 10 | Viewed by 2965
Abstract
Although many persons in the United States have acquired immunity to COVID-19, either through vaccination or infection with SARS-CoV-2, COVID-19 will pose an ongoing threat to non-immune persons so long as disease transmission continues. We can estimate when sustained disease transmission will end [...] Read more.
Although many persons in the United States have acquired immunity to COVID-19, either through vaccination or infection with SARS-CoV-2, COVID-19 will pose an ongoing threat to non-immune persons so long as disease transmission continues. We can estimate when sustained disease transmission will end in a population by calculating the population-specific basic reproduction number 0, the expected number of secondary cases generated by an infected person in the absence of any interventions. The value of 0 relates to a herd immunity threshold (HIT), which is given by 11/0. When the immune fraction of a population exceeds this threshold, sustained disease transmission becomes exponentially unlikely (barring mutations allowing SARS-CoV-2 to escape immunity). Here, we report state-level 0 estimates obtained using Bayesian inference. Maximum a posteriori estimates range from 7.1 for New Jersey to 2.3 for Wyoming, indicating that disease transmission varies considerably across states and that reaching herd immunity will be more difficult in some states than others. 0 estimates were obtained from compartmental models via the next-generation matrix approach after each model was parameterized using regional daily confirmed case reports of COVID-19 from 21 January 2020 to 21 June 2020. Our 0 estimates characterize the infectiousness of ancestral strains, but they can be used to determine HITs for a distinct, currently dominant circulating strain, such as SARS-CoV-2 variant Delta (lineage B.1.617.2), if the relative infectiousness of the strain can be ascertained. On the basis of Delta-adjusted HITs, vaccination data, and seroprevalence survey data, we found that no state had achieved herd immunity as of 20 September 2021. Full article
(This article belongs to the Special Issue Transmission Dynamics of Coronavirus Disease)
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13 pages, 2939 KiB  
Article
Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells
by Lin Yang, Xiaohua Liu, Liying Zhang, Xue Li, Xinwei Zhang, Guyu Niu, Weilong Ji, Si Chen, Hongsheng Ouyang and Linzhu Ren
Viruses 2022, 14(1), 156; https://doi.org/10.3390/v14010156 - 15 Jan 2022
Cited by 8 | Viewed by 2401
Abstract
Tripartite motif protein 21 (TRIM21) is an interferon-inducible E3 ligase, containing one RING finger domain, one B-box motif, one coiled-coil domain at the N-terminal, as well as one PRY domain and one SPRY domain at the C-terminal. TRIM21 is expressed in many tissues [...] Read more.
Tripartite motif protein 21 (TRIM21) is an interferon-inducible E3 ligase, containing one RING finger domain, one B-box motif, one coiled-coil domain at the N-terminal, as well as one PRY domain and one SPRY domain at the C-terminal. TRIM21 is expressed in many tissues and plays an important role in systemic autoimmunity. However, TRIM21 plays different roles in different virus infections. In this study, we evaluate the relationship between porcine TRIM21 and PCV2 infection as well as host immune responses. We found that PCV2 infection modulated the expression of porcine TRIM21. TRIM21 can enhance interferons and proinflammatory factors and decrease cellular apoptosis in PCV2-infected cells. These results indicate that porcine TRIM21 plays a critical role in enhancing PCV2 infection, which is a promising target for controlling and developing the treatment of PCV2 infection. Full article
(This article belongs to the Special Issue State-of-the-Art Porcine Virus Research in China)
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19 pages, 1213 KiB  
Review
Review of Oral Rabies Vaccination of Dogs and Its Application in India
by Gowri Yale, Marwin Lopes, Shrikrishna Isloor, Jennifer R. Head, Stella Mazeri, Luke Gamble, Kinzang Dukpa, Gyanendra Gongal and Andrew D. Gibson
Viruses 2022, 14(1), 155; https://doi.org/10.3390/v14010155 - 14 Jan 2022
Cited by 15 | Viewed by 6408
Abstract
Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. [...] Read more.
Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state. Full article
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11 pages, 2389 KiB  
Brief Report
Prevalence of SARS-CoV-2 Variants of Concern and Variants of Interest in COVID-19 Breakthrough Infections in a Hospital in Monterrey, Mexico
by Kame A. Galán-Huerta, Samantha Flores-Treviño, Daniel Salas-Treviño, Paola Bocanegra-Ibarias, Ana M. Rivas-Estilla, Eduardo Pérez-Alba, Sonia A. Lozano-Sepúlveda, Daniel Arellanos-Soto and Adrián Camacho-Ortiz
Viruses 2022, 14(1), 154; https://doi.org/10.3390/v14010154 - 14 Jan 2022
Cited by 7 | Viewed by 2826
Abstract
SARS-CoV-2 variants of concern (VOCs) or of interest (VOIs) causing vaccine breakthrough infections pose an increased risk to worldwide public health. An observational case-control study was performed of SARS-CoV-2 vaccine breakthrough infections in hospitalized or ambulatory patients in Monterrey, Mexico, from April through [...] Read more.
SARS-CoV-2 variants of concern (VOCs) or of interest (VOIs) causing vaccine breakthrough infections pose an increased risk to worldwide public health. An observational case-control study was performed of SARS-CoV-2 vaccine breakthrough infections in hospitalized or ambulatory patients in Monterrey, Mexico, from April through August 2021. Vaccination breakthrough was defined as a SARS-CoV-2 infection that occurred any time after 7 days of inoculation with partial (e.g., first dose of two-dose vaccines) or complete immunization (e.g., second dose of two-dose vaccines or single-dose vaccine, accordingly). Case group patients (n = 53) had partial or complete vaccination schemes with CanSino (45%), Sinovac (19%), Pfizer/BioNTech (15%), and AstraZeneca/Oxford (15%). CanSino was administered most frequently in ambulatory patients (p < 0.01). The control group (n = 19) received no COVID-19 vaccines. Among SARS-CoV-2 variants detected by whole-genome sequencing, VOC Delta B.1.617.2 predominated in vaccinated ambulatory patients (p < 0.01) and AY.4 in hospitalized patients (p = 0.04); VOI Mu B.1.621 was detected in four (7.55%) vaccinated patients. SARS-CoV-2 breakthrough infections in our hospital occurred mostly in patients vaccinated with CanSino due to the higher prevalence of CanSino vaccine administration in our population. These patients developed mild COVID-19 symptoms not requiring hospitalization. The significance of this study lies on the detection of SARS-CoV-2 variants compromising the efficacy of local immunization therapies in Monterrey, Mexico. Full article
(This article belongs to the Special Issue SARS-CoV-2 and COVID-19 in Latin America)
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17 pages, 58698 KiB  
Article
Actin Contributes to the Hyperexpression of Baculovirus Polyhedrin (polh) and p10 as a Component of Transcription Initiation Complex (TIC)
by Nan Chen, Guanping Chen, Xiangshuo Kong and Xiaofeng Wu
Viruses 2022, 14(1), 153; https://doi.org/10.3390/v14010153 - 14 Jan 2022
Cited by 1 | Viewed by 2343
Abstract
Hyperexpression of polh and p10, two very late genes, is one of the remarkable characteristics in the baculovirus life cycle. However, the mechanisms underlying the hyperexpression of these two genes are still incompletely understood. In this study, actin was identified as a [...] Read more.
Hyperexpression of polh and p10, two very late genes, is one of the remarkable characteristics in the baculovirus life cycle. However, the mechanisms underlying the hyperexpression of these two genes are still incompletely understood. In this study, actin was identified as a highly potential binding partner of polh and p10 promoters by conducting DNA pull-down and LC–MS/MS analyses. Inhibiting actin dynamics delayed and decreased the transcription of polh and p10. Actin interacted with viral RNA polymerase and transcription regulators, and the nuclear import of viral polymerase was inhibited with the disruption of actin dynamics. Simultaneously, the high enrichment of actin in polh and p10 promoters discovered via a chromatin immunoprecipitation (ChIP) assay indicated that actin was a component of the viral polymerase TIC. Moreover, overexpression of actin surprisingly upregulated the expression of luciferase (Luc) under the control of polh and p10 promoters. Taken together, actin participated in the hyperexpression of polh and p10 as a component of TIC. These results facilitate the promotion of the expression efficiency of foreign genes in the baculovirus expression vector system (BEVS). Full article
(This article belongs to the Special Issue State-of-the-Art Insect Viruses Research in China)
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20 pages, 2289 KiB  
Review
HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread
by Svetlana Kalinichenko, Dmitriy Komkov and Dmitriy Mazurov
Viruses 2022, 14(1), 152; https://doi.org/10.3390/v14010152 - 14 Jan 2022
Cited by 20 | Viewed by 10423
Abstract
So far, only two retroviruses, human immunodeficiency virus (HIV) (type 1 and 2) and human T-cell lymphotropic virus type 1 (HTLV-1), have been recognized as pathogenic for humans. Both viruses mainly infect CD4+ T lymphocytes. HIV replication induces the apoptosis of CD4 lymphocytes, [...] Read more.
So far, only two retroviruses, human immunodeficiency virus (HIV) (type 1 and 2) and human T-cell lymphotropic virus type 1 (HTLV-1), have been recognized as pathogenic for humans. Both viruses mainly infect CD4+ T lymphocytes. HIV replication induces the apoptosis of CD4 lymphocytes, leading to the development of acquired immunodeficiency syndrome (AIDS). After a long clinical latency period, HTLV-1 can transform lymphocytes, with subsequent uncontrolled proliferation and the manifestation of a disease called adult T-cell leukemia (ATLL). Certain infected patients develop neurological autoimmune disorder called HTLV-1-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP). Both viruses are transmitted between individuals via blood transfusion, tissue/organ transplantation, breastfeeding, and sexual intercourse. Within the host, these viruses can spread utilizing either cell-free or cell-to-cell modes of transmission. In this review, we discuss the mechanisms and importance of each mode of transmission for the biology of HIV-1 and HTLV-1. Full article
(This article belongs to the Special Issue 40 Years Anniversary of HTLV-1 Discovery)
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21 pages, 3839 KiB  
Article
Four Novel Mycoviruses from the Hypovirulent Botrytis cinerea SZ-2-3y Isolate from Paris polyphylla: Molecular Characterisation and Mitoviral Sequence Transboundary Entry into Plants
by Qiong Wang, Qi Zou, Zhaoji Dai, Ni Hong, Guoping Wang and Liping Wang
Viruses 2022, 14(1), 151; https://doi.org/10.3390/v14010151 - 14 Jan 2022
Cited by 10 | Viewed by 2626
Abstract
A hypovirulent SZ-2-3y strain isolated from diseased Paris polyphylla was identified as Botrytis cinerea. Interestingly, SZ-2-3y was coinfected with a mitovirus, two botouliviruses, and a 3074 nt fusarivirus, designated Botrytis cinerea fusarivirus 8 (BcFV8); it shares an 87.2% sequence identity with the [...] Read more.
A hypovirulent SZ-2-3y strain isolated from diseased Paris polyphylla was identified as Botrytis cinerea. Interestingly, SZ-2-3y was coinfected with a mitovirus, two botouliviruses, and a 3074 nt fusarivirus, designated Botrytis cinerea fusarivirus 8 (BcFV8); it shares an 87.2% sequence identity with the previously identified Botrytis cinerea fusarivirus 6 (BcFV6). The full-length 2945 nt genome sequence of the mitovirus, termed Botrytis cinerea mitovirus 10 (BcMV10), shares a 54% sequence identity with Fusarium boothii mitovirus 1 (FbMV1), and clusters with fungus mitoviruses, plant mitoviruses and plant mitochondria; hence BcMV10 is a new Mitoviridae member. The full-length 2759 nt and 2812 nt genome sequences of the other two botouliviruses, named Botrytis cinerea botoulivirus 18 and 19 (BcBoV18 and 19), share a 40% amino acid sequence identity with RNA-dependent RNA polymerase protein (RdRp), and these are new members of the Botoulivirus genus of Botourmiaviridae. Horizontal transmission analysis showed that BcBoV18, BcBoV19 and BcFV8 are not related to hypovirulence, suggesting that BcMV10 may induce hypovirulence. Intriguingly, a partial BcMV10 sequence was detected in cucumber plants inoculated with SZ-2-3y mycelium or pXT1/BcMV10 agrobacterium. In conclusion, we identified a hypovirulent SZ-2-3y fungal strain from P. polyphylla, coinfected with four novel mycoviruses that could serve as potential biocontrol agents. Our findings provide evidence of cross-kingdom mycoviral sequence transmission. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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13 pages, 611 KiB  
Review
Exploring the Role of Innate Lymphocytes in the Immune System of Bats and Virus-Host Interactions
by Wan Rong Sia, Yichao Zheng, Fei Han, Shiwei Chen, Shaohua Ma, Lin-Fa Wang and Edwin Leeansyah
Viruses 2022, 14(1), 150; https://doi.org/10.3390/v14010150 - 14 Jan 2022
Cited by 9 | Viewed by 6342
Abstract
Bats are reservoirs of a large number of viruses of global public health significance, including the ancestral virus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the causative agent of coronavirus disease 2019 (COVID-19). Although bats are natural carriers of multiple pathogenic [...] Read more.
Bats are reservoirs of a large number of viruses of global public health significance, including the ancestral virus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the causative agent of coronavirus disease 2019 (COVID-19). Although bats are natural carriers of multiple pathogenic viruses, they rarely display signs of disease. Recent insights suggest that bats have a more balanced host defense and tolerance system to viral infections that may be linked to the evolutionary adaptation to powered flight. Therefore, a deeper understanding of bat immune system may provide intervention strategies to prevent zoonotic disease transmission and to identify new therapeutic targets. Similar to other eutherian mammals, bats have both innate and adaptive immune systems that have evolved to detect and respond to invading pathogens. Bridging these two systems are innate lymphocytes, which are highly abundant within circulation and barrier tissues. These cells share the characteristics of both innate and adaptive immune cells and are poised to mount rapid effector responses. They are ideally suited as the first line of defense against early stages of viral infections. Here, we will focus on the current knowledge of innate lymphocytes in bats, their function, and their potential role in host–pathogen interactions. Moreover, given that studies into bat immune systems are often hindered by a lack of bat-specific research tools, we will discuss strategies that may aid future research in bat immunity, including the potential use of organoid models to delineate the interplay between innate lymphocytes, bat viruses, and host tolerance. Full article
(This article belongs to the Special Issue Host Diversity and Responses to Bat-Associated Viruses)
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13 pages, 2518 KiB  
Article
Bacterial Toxins from Staphylococcus aureus and Bordetella bronchiseptica Predispose the Horse’s Respiratory Tract to Equine Herpesvirus Type 1 Infection
by Eline Van Crombrugge, Emma Vanbeylen, Jolien Van Cleemput, Wim Van den Broeck, Kathlyn Laval and Hans Nauwynck
Viruses 2022, 14(1), 149; https://doi.org/10.3390/v14010149 - 14 Jan 2022
Cited by 1 | Viewed by 2337
Abstract
Respiratory disease in horses is caused by a multifactorial complex of infectious agents and environmental factors. An important pathogen in horses is equine herpesvirus type 1 (EHV-1). During co-evolution with this ancient alphaherpesvirus, the horse’s respiratory tract has developed multiple antiviral barriers. However, [...] Read more.
Respiratory disease in horses is caused by a multifactorial complex of infectious agents and environmental factors. An important pathogen in horses is equine herpesvirus type 1 (EHV-1). During co-evolution with this ancient alphaherpesvirus, the horse’s respiratory tract has developed multiple antiviral barriers. However, these barriers can become compromised by environmental threats. Pollens and mycotoxins enhance mucosal susceptibility to EHV-1 by interrupting cell junctions, allowing the virus to reach its basolateral receptor. Whether bacterial toxins also play a role in this impairment has not been studied yet. Here, we evaluated the role of α-hemolysin (Hla) and adenylate cyclase (ACT), toxins derived from the facultative pathogenic bacterium Staphylococcus aureus (S. aureus) and the primary pathogen Bordetella bronchiseptica (B. bronchiseptica), respectively. Equine respiratory mucosal explants were cultured at an air–liquid interface and pretreated with these toxins, prior to EHV-1 inoculation. Morphological analysis of hematoxylin–eosin (HE)-stained sections of the explants revealed a decreased epithelial thickness upon treatment with both toxins. Additionally, the Hla toxin induced detachment of epithelial cells and a partial loss of cilia. These morphological changes were correlated with increased EHV-1 replication in the epithelium, as assessed by immunofluorescent stainings and confocal microscopy. In view of these results, we argue that the ACT and Hla toxins increase the susceptibility of the epithelium to EHV-1 by disrupting the epithelial barrier function. In conclusion, this study is the first to report that bacterial exotoxins increase the horse’s sensitivity to EHV-1 infection. Therefore, we propose that horses suffering from infection by S. aureus or B. bronchiseptica may be more susceptible to EHV-1 infection. Full article
(This article belongs to the Special Issue Animal Herpesviruses Pathogenesis and Immunity)
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7 pages, 237 KiB  
Communication
Detection of Porcine Respirovirus 1 (PRV1) in Poland: Incidence of Co-Infections with Influenza A Virus (IAV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in Herds with a Respiratory Disease
by Aleksandra Woźniak, Piotr Cybulski, Lilla Denes, Gyula Balka and Tomasz Stadejek
Viruses 2022, 14(1), 148; https://doi.org/10.3390/v14010148 - 14 Jan 2022
Cited by 13 | Viewed by 2144
Abstract
Porcine respirovirus 1 (PRV1) is also known as porcine parainfluenza virus 1 (PPIV1). The prevalence and the role of PRV1 infections for pig health is largely unknown. In order to assess the PRV1 prevalence in Poland, nasal swabs and oral fluids collected from [...] Read more.
Porcine respirovirus 1 (PRV1) is also known as porcine parainfluenza virus 1 (PPIV1). The prevalence and the role of PRV1 infections for pig health is largely unknown. In order to assess the PRV1 prevalence in Poland, nasal swabs and oral fluids collected from pigs from 30 farms were examined with RT real-time PCR. Additionally, IAV and PRRSV infection statuses of PRV1-positive samples were examined. The results showed that the virus is highly prevalent (76.7% farms positive) and different patterns of PRV1 circulation in herds with mild–moderate respiratory disease were observed. Co-infections with IAV and PRRSV were infrequent and detected in 8 (23.5%) and 4 (11.8%) out of 34 PRV1-positive nasal swab pools from diseased pens, respectively. In one pen PRV1, IAV, and PRRSV were detected at the same time. Interestingly, PRV1 mean Ct value in samples with co-infections was significantly lower (29.8 ± 3.1) than in samples with a single PRV1 infection (32.5 ± 3.6) (p < 0.05), which suggested higher virus replication in these populations. On the other hand, the virus detection in pig populations exhibiting respiratory clinical signs, negative for PRRSV and IAV, suggests that PRV1 should be involved in differential diagnosis of respiratory problems. Full article
(This article belongs to the Special Issue State-of-the-Art Animal Virus Research in Poland)
11 pages, 1723 KiB  
Article
IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice
by Abenaya Muralidharan, Md Bashir Uddin, Christopher Bauer, Wenzhe Wu, Xiaoyong Bao and Keer Sun
Viruses 2022, 14(1), 147; https://doi.org/10.3390/v14010147 - 14 Jan 2022
Cited by 2 | Viewed by 2133
Abstract
The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 [...] Read more.
The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic Ifng−/− mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic Ifng−/− mice in the absence of RSV infection. Furthermore, neither WT nor Ifng−/− mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice. Full article
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18 pages, 997 KiB  
Article
Extending the Coding Potential of Viral Genomes with Overlapping Antisense ORFs: A Case for the De Novo Creation of the Gene Encoding the Antisense Protein ASP of HIV-1
by Angelo Pavesi and Fabio Romerio
Viruses 2022, 14(1), 146; https://doi.org/10.3390/v14010146 - 14 Jan 2022
Cited by 3 | Viewed by 1827
Abstract
Gene overprinting occurs when point mutations within a genomic region with an existing coding sequence create a new one in another reading frame. This process is quite frequent in viral genomes either to maximize the amount of information that they encode or in [...] Read more.
Gene overprinting occurs when point mutations within a genomic region with an existing coding sequence create a new one in another reading frame. This process is quite frequent in viral genomes either to maximize the amount of information that they encode or in response to strong selective pressure. The most frequent scenario involves two different reading frames in the same DNA strand (sense overlap). Much less frequent are cases of overlapping genes that are encoded on opposite DNA strands (antisense overlap). One such example is the antisense ORF, asp in the minus strand of the HIV-1 genome overlapping the env gene. The asp gene is highly conserved in pandemic HIV-1 strains of group M, and it is absent in non-pandemic HIV-1 groups, HIV-2, and lentiviruses infecting non-human primates, suggesting that the ~190-amino acid protein that is expressed from this gene (ASP) may play a role in virus spread. While the function of ASP in the virus life cycle remains to be elucidated, mounting evidence from several research groups indicates that ASP is expressed in vivo. There are two alternative hypotheses that could be envisioned to explain the origin of the asp ORF. On one hand, asp may have originally been present in the ancestor of contemporary lentiviruses, and subsequently lost in all descendants except for most HIV-1 strains of group M due to selective advantage. Alternatively, the asp ORF may have originated very recently with the emergence of group M HIV-1 strains from SIVcpz. Here, we used a combination of computational and statistical approaches to study the genomic region of env in primate lentiviruses to shed light on the origin, structure, and sequence evolution of the asp ORF. The results emerging from our studies support the hypothesis of a recent de novo addition of the antisense ORF to the HIV-1 genome through a process that entailed progressive removal of existing internal stop codons from SIV strains to HIV-1 strains of group M, and fine tuning of the codon sequence in env that reduced the chances of new stop codons occurring in asp. Altogether, the study supports the notion that the HIV-1 asp gene encodes an accessory protein, providing a selective advantage to the virus. Full article
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23 pages, 31405 KiB  
Article
HERV-W Envelope Triggers Abnormal Dopaminergic Neuron Process through DRD2/PP2A/AKT1/GSK3 for Schizophrenia Risk
by Qiujin Yan, Xiulin Wu, Ping Zhou, Yan Zhou, Xuhang Li, Zhongchun Liu, Huawei Tan, Wei Yao, Yaru Xia and Fan Zhu
Viruses 2022, 14(1), 145; https://doi.org/10.3390/v14010145 - 14 Jan 2022
Cited by 13 | Viewed by 3047
Abstract
An increasing number of studies have begun considering human endogenous retroviruses (HERVs) as potential pathogenic phenomena. Our previous research suggests that HERV-W Envelope (HERV-W ENV), a HERV-W family envelope protein, is elevated in schizophrenia patients and contributes to the pathophysiology of [...] Read more.
An increasing number of studies have begun considering human endogenous retroviruses (HERVs) as potential pathogenic phenomena. Our previous research suggests that HERV-W Envelope (HERV-W ENV), a HERV-W family envelope protein, is elevated in schizophrenia patients and contributes to the pathophysiology of schizophrenia. The dopamine (DA) hypothesis is the cornerstone in research and clinical practice related to schizophrenia. Here, we found that the concentration of DA and the expression of DA receptor D2 (DRD2) were significantly higher in schizophrenia patients than in healthy individuals. Intriguingly, there was a positive correlation between HERV-W ENV and DA concentration. Depth analyses showed that there was a marked consistency between HERV-W ENV and DRD2 in schizophrenia. Studies in vitro indicated that HERV-W ENV could increase the DA concentration by regulating DA metabolism and induce the expression of DRD2. Co-IP assays and laser confocal scanning microscopy indicated cellular colocalization and a direct interaction between DRD2 and HERV-W ENV. Additionally, HERV-W ENV caused structural and functional abnormalities of DA neurons. Further studies showed that HERV-W ENV could trigger the PP2A/AKT1/GSK3 pathway via DRD2. A whole-cell patch-clamp analysis suggested that HERV-W ENV enhanced sodium influx through DRD2. In conclusion, we uncovered a relationship between HERV-W ENV and the dopaminergic system in the DA neurons. Considering that GNbAC1, a selective monoclonal antibody to the MSRV-specific epitope, has been promised as a therapy for treating type 1 diabetes and multiple sclerosis (MS) in clinical trials, understanding the precise function of HERV-W ENV in the dopaminergic system may provide new insights into the treatment of schizophrenia. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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10 pages, 1343 KiB  
Communication
Antigenicity of the Mu (B.1.621) and A.2.5 SARS-CoV-2 Spikes
by Debashree Chatterjee, Alexandra Tauzin, Annemarie Laumaea, Shang Yu Gong, Yuxia Bo, Aurélie Guilbault, Guillaume Goyette, Catherine Bourassa, Gabrielle Gendron-Lepage, Halima Medjahed, Jonathan Richard, Sandrine Moreira, Marceline Côté and Andrés Finzi
Viruses 2022, 14(1), 144; https://doi.org/10.3390/v14010144 - 14 Jan 2022
Cited by 8 | Viewed by 2906
Abstract
The rapid emergence of SARS-CoV-2 variants is fueling the recent waves of the COVID-19 pandemic. Here, we assessed ACE2 binding and antigenicity of Mu (B.1.621) and A.2.5 Spikes. Both these variants carry some mutations shared by other emerging variants. Some of the pivotal [...] Read more.
The rapid emergence of SARS-CoV-2 variants is fueling the recent waves of the COVID-19 pandemic. Here, we assessed ACE2 binding and antigenicity of Mu (B.1.621) and A.2.5 Spikes. Both these variants carry some mutations shared by other emerging variants. Some of the pivotal mutations such as N501Y and E484K in the receptor-binding domain (RBD) detected in B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) are now present within the Mu variant. Similarly, the L452R mutation of B.1.617.2 (Delta) variant is present in A.2.5. In this study, we observed that these Spike variants bound better to the ACE2 receptor in a temperature-dependent manner. Pseudoviral particles bearing the Spike of Mu were similarly neutralized by plasma from vaccinated individuals than those carrying the Beta (B.1.351) and Delta (B.1.617.2) Spikes. Altogether, our results indicate the importance of measuring critical parameters such as ACE2 interaction, plasma recognition and neutralization ability of each emerging variant. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
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11 pages, 1372 KiB  
Brief Report
Detection of Enterovirus D68 in Wastewater Samples from the UK between July and November 2021
by Alison Tedcastle, Thomas Wilton, Elaine Pegg, Dimitra Klapsa, Erika Bujaki, Ryan Mate, Martin Fritzsche, Manasi Majumdar and Javier Martin
Viruses 2022, 14(1), 143; https://doi.org/10.3390/v14010143 - 13 Jan 2022
Cited by 21 | Viewed by 3100
Abstract
Infection with enterovirus D68 (EV-D68) has been linked with severe neurological disease such as acute flaccid myelitis (AFM) in recent years. However, active surveillance for EV-D68 is lacking, which makes full assessment of this association difficult. Although a high number of EV-D68 infections [...] Read more.
Infection with enterovirus D68 (EV-D68) has been linked with severe neurological disease such as acute flaccid myelitis (AFM) in recent years. However, active surveillance for EV-D68 is lacking, which makes full assessment of this association difficult. Although a high number of EV-D68 infections were expected in 2020 based on the EV-D68′s known biannual circulation patterns, no apparent increase in EV-D68 detections or AFM cases was observed during 2020. We describe an upsurge of EV-D68 detections in wastewater samples from the United Kingdom between July and November 2021 mirroring the recently reported rise in EV-D68 detections in clinical samples from various European countries. We provide the first publicly available 2021 EV-D68 sequences showing co-circulation of EV-D68 strains from genetic clade D and sub-clade B3 as in previous years. Our results show the value of environmental surveillance (ES) for the early detection of circulating and clinically relevant human viruses. The use of a next-generation sequencing (NGS) approach helped us to estimate the prevalence of EV-D68 viruses among EV strains from other EV serotypes and to detect EV-D68 minor variants. The utility of ES at reducing gaps in virus surveillance for EV-D68 and the possible impact of nonpharmaceutical interventions introduced to control the COVID-19 pandemic on EV-D68 transmission dynamics are discussed. Full article
(This article belongs to the Special Issue Surveillance for Polio and Non-polio Enteroviruses)
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22 pages, 9300 KiB  
Article
Ebola Virus GP Activates Endothelial Cells via Host Cytoskeletal Signaling Factors
by Benedicte Mpia Moni, Yasuteru Sakurai and Jiro Yasuda
Viruses 2022, 14(1), 142; https://doi.org/10.3390/v14010142 - 13 Jan 2022
Cited by 4 | Viewed by 3172
Abstract
Ebola virus disease (EVD) is a lethal disease caused by the highly pathogenic Ebola virus (EBOV), and its major symptoms in severe cases include vascular leakage and hemorrhage. These symptoms are caused by abnormal activation and disruption of endothelial cells (ECs) whose mediators [...] Read more.
Ebola virus disease (EVD) is a lethal disease caused by the highly pathogenic Ebola virus (EBOV), and its major symptoms in severe cases include vascular leakage and hemorrhage. These symptoms are caused by abnormal activation and disruption of endothelial cells (ECs) whose mediators include EBOV glycoprotein (GP) without the need for viral replication. However, the detailed molecular mechanisms underlying virus–host interactions remain largely unknown. Here, we show that EBOV-like particles (VLPs) formed by GP, VP40, and NP activate ECs in a GP-dependent manner, as demonstrated by the upregulation of intercellular adhesion molecules-1 (ICAM-1) expression. VLPs-mediated ECs activation showed a different kinetic pattern from that of TNF-α-mediated activation and was associated with apoptotic ECs disruption. In contrast to TNF-α, VLPs induced ICAM-1 overexpression at late time points. Furthermore, screening of host cytoskeletal signaling inhibitors revealed that focal adhesion kinase inhibitors were found to be potent inhibitors of ICAM-1 expression mediated by both TNF-α and VLPs. Our results suggest that EBOV GP stimulates ECs to induce endothelial activation and dysfunction with the involvement of host cytoskeletal signaling factors, which represent potential therapeutic targets for EVD. Full article
(This article belongs to the Special Issue Antiviral Therapeutics for Emerging Viruses)
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23 pages, 599 KiB  
Review
Understanding Rhinovirus Circulation and Impact on Illness
by Camille Esneau, Alexandra Cate Duff and Nathan W. Bartlett
Viruses 2022, 14(1), 141; https://doi.org/10.3390/v14010141 - 13 Jan 2022
Cited by 31 | Viewed by 5768
Abstract
Rhinoviruses (RVs) have been reported as one of the main viral causes for severe respiratory illnesses that may require hospitalization, competing with the burden of other respiratory viruses such as influenza and RSV in terms of severity, economic cost, and resource utilization. With [...] Read more.
Rhinoviruses (RVs) have been reported as one of the main viral causes for severe respiratory illnesses that may require hospitalization, competing with the burden of other respiratory viruses such as influenza and RSV in terms of severity, economic cost, and resource utilization. With three species and 169 subtypes, RV presents the greatest diversity within the Enterovirus genus, and despite the efforts of the research community to identify clinically relevant subtypes to target therapeutic strategies, the role of species and subtype in the clinical outcomes of RV infection remains unclear. This review aims to collect and organize data relevant to RV illness in order to find patterns and links with species and/or subtype, with a specific focus on species and subtype diversity in clinical studies typing of respiratory samples. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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17 pages, 7316 KiB  
Article
Impact of Molecular Modification on the Efficiency of Recombinant Baculovirus Vector Invasion to Mammalian Cells and Its Immunogenicity in Mice
by Hao Zheng, Yong Pan, Xiong Wang, Weibin Tian, Lunguang Yao and Jingchen Sun
Viruses 2022, 14(1), 140; https://doi.org/10.3390/v14010140 - 13 Jan 2022
Cited by 2 | Viewed by 1981
Abstract
The baculovirus display system (BDS), an excellent eukaryotic surface display technology that offers the advantages of safety, efficiency, and economy, is widely used in biomedicine. A previous study using rBacmid-Δgp64-ires-gp64 expressed in low copy numbers of the gp64 gene achieved high-efficiency expression and [...] Read more.
The baculovirus display system (BDS), an excellent eukaryotic surface display technology that offers the advantages of safety, efficiency, and economy, is widely used in biomedicine. A previous study using rBacmid-Δgp64-ires-gp64 expressed in low copy numbers of the gp64 gene achieved high-efficiency expression and co-display of three fluorescent proteins (GFP, YFP, and mCherry). However, low expression of GP64 in recombinant baculoviruses also reduces the efficiency of recombinant baculovirus transduction into mammalian cells. In addition, the baculovirus promoter has no expression activity in mammalian cells and thus cannot meet the application requirements of baculoviral vectors for the BDS. Based on previous research, this study first determined the expression activity of promoters in insect Spodoptera frugiperda 9 cells and mammalian cells and successfully screened the very early promoter pie1 to mediate the co-expression of multiple genes. Second, utilizing the envelope display effect of the INVASIN and VSVG proteins, the efficiency of transduction of recombinant baculovirus particles into non-host cells was significantly improved. Finally, based on the above improvement, a recombinant baculovirus vector displaying four antigen proteins with high efficiency was constructed. Compared with traditional BDSs, the rBacmid-Δgp64 system exhibited increased display efficiency of the target protein by approximately 3-fold and induced an approximately 4-fold increase in the titer of serum antibodies to target antigens in Bal B/c mice. This study systematically explored the application of a new multi-gene co-display technology applicable to multi-vaccine research, and the results provide a foundation for the development of novel BDS technologies. Full article
(This article belongs to the Section Insect Viruses)
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16 pages, 2650 KiB  
Article
Neuroinflammatory Profiling in SIV-Infected Chinese-Origin Rhesus Macaques on Antiretroviral Therapy
by Antonio Solis-Leal, Summer Siddiqui, Fei Wu, Mahesh Mohan, Wenhui Hu, Lara A. Doyle-Meyers, Jason P. Dufour and Binhua Ling
Viruses 2022, 14(1), 139; https://doi.org/10.3390/v14010139 - 13 Jan 2022
Cited by 4 | Viewed by 2387
Abstract
The central nervous system (CNS) HIV reservoir is an obstacle to achieving an HIV cure. The basal ganglia harbor a higher frequency of SIV than other brain regions in the SIV-infected rhesus macaques of Chinese-origin (chRMs) even on suppressive combination antiretroviral therapy (ART). [...] Read more.
The central nervous system (CNS) HIV reservoir is an obstacle to achieving an HIV cure. The basal ganglia harbor a higher frequency of SIV than other brain regions in the SIV-infected rhesus macaques of Chinese-origin (chRMs) even on suppressive combination antiretroviral therapy (ART). Since residual HIV/SIV reservoir is associated with inflammation, we characterized the neuroinflammation by gene expression and systemic levels of inflammatory molecules in healthy controls and SIV-infected chRMs with or without ART. CCL2, IL-6, and IFN-γ were significantly reduced in the cerebrospinal fluid (CSF) of animals receiving ART. Moreover, there was a correlation between levels of CCL2 in plasma and CSF, suggesting the potential use of plasma CCL2 as a neuroinflammation biomarker. With higher SIV frequency, the basal ganglia of untreated SIV-infected chRMs showed an upregulation of secreted phosphoprotein 1 (SPP1), which could be an indicator of ongoing neuroinflammation. While ART greatly reduced neuroinflammation in general, proinflammatory genes, such as IL-9, were still significantly upregulated. These results expand our understanding of neuroinflammation and signaling in SIV-infected chRMs on ART, an excellent model to study HIV/SIV persistence in the CNS. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Viral Infections)
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16 pages, 11350 KiB  
Review
Human T-Cell Leukemia Virus Type 1 Envelope Protein: Post-Entry Roles in Viral Pathogenesis
by Victoria Maksimova and Amanda R. Panfil
Viruses 2022, 14(1), 138; https://doi.org/10.3390/v14010138 - 13 Jan 2022
Cited by 2 | Viewed by 3070
Abstract
Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and fatal CD4+ T-cell malignancy, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neurological disease. Disease progression in [...] Read more.
Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and fatal CD4+ T-cell malignancy, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neurological disease. Disease progression in infected individuals is the result of HTLV-1-driven clonal expansion of CD4+ T-cells and is generally associated with the activities of the viral oncoproteins Tax and Hbz. A closely related virus, HTLV-2, exhibits similar genomic features and the capacity to transform T-cells, but is non-pathogenic. In vitro, HTLV-1 primarily immortalizes or transforms CD4+ T-cells, while HTLV-2 displays a transformation tropism for CD8+ T-cells. This distinct tropism is recapitulated in infected people. Through comparative studies, the genetic determinant for this divergent tropism of HTLV-1/2 has been mapped to the viral envelope (Env). In this review, we explore the emerging roles for Env beyond initial viral entry and examine current perspectives on its contributions to HTLV-1-mediated disease development. Full article
(This article belongs to the Special Issue 40 Years Anniversary of HTLV-1 Discovery)
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22 pages, 4557 KiB  
Review
C Proteins: Controllers of Orderly Paramyxovirus Replication and of the Innate Immune Response
by Oliver Siering, Roberto Cattaneo and Christian K. Pfaller
Viruses 2022, 14(1), 137; https://doi.org/10.3390/v14010137 - 12 Jan 2022
Cited by 10 | Viewed by 3341
Abstract
Particles of many paramyxoviruses include small amounts of proteins with a molecular weight of about 20 kDa. These proteins, termed “C”, are basic, have low amino acid homology and some secondary structure conservation. C proteins are encoded in alternative reading frames of the [...] Read more.
Particles of many paramyxoviruses include small amounts of proteins with a molecular weight of about 20 kDa. These proteins, termed “C”, are basic, have low amino acid homology and some secondary structure conservation. C proteins are encoded in alternative reading frames of the phosphoprotein gene. Some viruses express nested sets of C proteins that exert their functions in different locations: In the nucleus, they interfere with cellular transcription factors that elicit innate immune responses; in the cytoplasm, they associate with viral ribonucleocapsids and control polymerase processivity and orderly replication, thereby minimizing the activation of innate immunity. In addition, certain C proteins can directly bind to, and interfere with the function of, several cytoplasmic proteins required for interferon induction, interferon signaling and inflammation. Some C proteins are also required for efficient virus particle assembly and budding. C-deficient viruses can be grown in certain transformed cell lines but are not pathogenic in natural hosts. C proteins affect the same host functions as other phosphoprotein gene-encoded proteins named V but use different strategies for this purpose. Multiple independent systems to counteract host defenses may ensure efficient immune evasion and facilitate virus adaptation to new hosts and tissue environments. Full article
(This article belongs to the Special Issue Nucleocapsids of Paramyxoviruses)
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17 pages, 1439 KiB  
Article
Efficacy of Corticosteroid Therapy for HTLV-1-Associated Myelopathy: A Randomized Controlled Trial (HAMLET-P)
by Junji Yamauchi, Kenichiro Tanabe, Tomoo Sato, Masanori Nakagawa, Eiji Matsuura, Yoshio Tsuboi, Keiko Tamaki, Hirokuni Sakima, Satoshi Ishihara, Yuki Ohta, Naoki Matsumoto, Kenichi Kono, Naoko Yagishita, Natsumi Araya, Katsunori Takahashi, Yasuo Kunitomo, Misako Nagasaka, Ariella Coler-Reilly, Yasuhiro Hasegawa, Abelardo Araujo, Steven Jacobson, Maria Fernanda Rios Grassi, Bernardo Galvão-Castro, Martin Bland, Graham P. Taylor, Fabiola Martin and Yoshihisa Yamanoadd Show full author list remove Hide full author list
Viruses 2022, 14(1), 136; https://doi.org/10.3390/v14010136 - 12 Jan 2022
Cited by 15 | Viewed by 3756
Abstract
Corticosteroids are most commonly used to treat HTLV-1-associated myelopathy (HAM); however, their clinical efficacy has not been tested in randomized clinical trials. This randomized controlled trial included 8 and 30 HAM patients with rapidly and slowly progressing walking disabilities, respectively. Rapid progressors were [...] Read more.
Corticosteroids are most commonly used to treat HTLV-1-associated myelopathy (HAM); however, their clinical efficacy has not been tested in randomized clinical trials. This randomized controlled trial included 8 and 30 HAM patients with rapidly and slowly progressing walking disabilities, respectively. Rapid progressors were assigned (1:1) to receive or not receive a 3-day course of intravenous methylprednisolone in addition to oral prednisolone therapy. Meanwhile, slow progressors were assigned (1:1) to receive oral prednisolone or placebo. The primary outcomes were a composite of ≥1-grade improvement in the Osame Motor Disability Score or ≥30% improvement in the 10 m walking time (10 mWT) at week 2 for rapid progressors and changes from baseline in 10 mWT at week 24 for slow progressors. In the rapid progressor trial, all four patients with but only one of four without intravenous methylprednisolone achieved the primary outcome (p = 0.14). In the slow progressor trial, the median changes in 10 mWT were −13.8% (95% CI: −20.1–−7.1; p < 0.001) and −6.0% (95% CI: −12.8–1.3; p = 0.10) with prednisolone and placebo, respectively (p for between-group difference = 0.12). Whereas statistical significance was not reached for the primary endpoints, the overall data indicated the benefit of corticosteroid therapy. (Registration number: UMIN000023798, UMIN000024085) Full article
(This article belongs to the Special Issue HTLV-1 and HTLV-1-Associated Diseases)
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