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Volume 16
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Viruses, Volume 16, Issue 1 (January 2024) – 166 articles

Cover Story (view full-size image): It has been reported that platelets interact with and endocytose different viruses. However, the importance of this to thrombosis is unclear. We used the EcoHIV model to probe the effects of viremia on mouse platelets. EcoHIV caused a viral infection with an active virus in the spleen and a humoral immune response. However, the circulating virus was cleared rapidly and was undetectable by Day 7. No effects on platelets were detected in vivo, using several activation metrics. To explain our results, we showed that mouse platelets did not express the receptor for EcoHIV, murine Cationic Amino acid Transporter 1 (mCAT-1). Further, we showed that previous studies showing platelet activation and thrombocytopenia were caused by impurities in the Polyethylene Glycol (PEG) that precipitated EcoHIV preparations. View this paper
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17 pages, 2143 KiB  
Review
Utilization of Bacteriophage phi6 for the Production of High-Quality Double-Stranded RNA Molecules
by Alesia A. Levanova and Minna M. Poranen
Viruses 2024, 16(1), 166; https://doi.org/10.3390/v16010166 - 22 Jan 2024
Cited by 1 | Viewed by 2015
Abstract
Double-stranded RNA (dsRNA) molecules are mediators of RNA interference (RNAi) in eukaryotic cells. RNAi is a conserved mechanism of post-transcriptional silencing of genes cognate to the sequences of the applied dsRNA. RNAi-based therapeutics for the treatment of rare hereditary diseases have recently emerged, [...] Read more.
Double-stranded RNA (dsRNA) molecules are mediators of RNA interference (RNAi) in eukaryotic cells. RNAi is a conserved mechanism of post-transcriptional silencing of genes cognate to the sequences of the applied dsRNA. RNAi-based therapeutics for the treatment of rare hereditary diseases have recently emerged, and the first sprayable dsRNA biopesticide has been proposed for registration. The range of applications of dsRNA molecules will likely expand in the future. Therefore, cost-effective methods for the efficient large-scale production of high-quality dsRNA are in demand. Conventional approaches to dsRNA production rely on the chemical or enzymatic synthesis of single-stranded (ss)RNA molecules with a subsequent hybridization of complementary strands. However, the yield of properly annealed biologically active dsRNA molecules is low. As an alternative approach, we have developed methods based on components derived from bacteriophage phi6, a dsRNA virus encoding RNA-dependent RNA polymerase (RdRp). Phi6 RdRp can be harnessed for the enzymatic production of high-quality dsRNA molecules. The isolated RdRp efficiently synthesizes dsRNA in vitro on a heterologous ssRNA template of any length and sequence. To scale up dsRNA production, we have developed an in vivo system where phi6 polymerase complexes produce target dsRNA molecules inside Pseudomonas cells. Full article
(This article belongs to the Special Issue Discovery, Classification, and Early Research on the Lipid-Containing, Double-Stranded RNA Bacteriophage φ6)
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19 pages, 3155 KiB  
Article
The Inovirus Pf4 Triggers Antiviral Responses and Disrupts the Proliferation of Airway Basal Epithelial Cells
by Medeea C. Popescu, Naomi L. Haddock, Elizabeth B. Burgener, Laura S. Rojas-Hernandez, Gernot Kaber, Aviv Hargil, Paul L. Bollyky and Carlos E. Milla
Viruses 2024, 16(1), 165; https://doi.org/10.3390/v16010165 - 22 Jan 2024
Cited by 1 | Viewed by 1844
Abstract
Background: The inovirus Pf4 is a lysogenic bacteriophage of Pseudomonas aeruginosa (Pa). People with Cystic Fibrosis (pwCF) experience chronic airway infection with Pa and a significant proportion have high numbers of Pf4 in their airway secretions. Given the known severe damage [...] Read more.
Background: The inovirus Pf4 is a lysogenic bacteriophage of Pseudomonas aeruginosa (Pa). People with Cystic Fibrosis (pwCF) experience chronic airway infection with Pa and a significant proportion have high numbers of Pf4 in their airway secretions. Given the known severe damage in the airways of Pa-infected pwCF, we hypothesized a high Pf4 burden can affect airway healing and inflammatory responses. In the airway, basal epithelial cells (BCs) are a multipotent stem cell population critical to epithelium homeostasis and repair. We sought to investigate the transcriptional responses of BCs under conditions that emulate infection with Pa and exposure to high Pf4 burden. Methods: Primary BCs isolated from pwCF and wild-type (WT) donors were cultured in vitro and exposed to Pf4 or bacterial Lipopolysaccharide (LPS) followed by transcriptomic and functional assays. Results: We found that BCs internalized Pf4 and this elicits a strong antiviral response as well as neutrophil chemokine production. Further, we found that BCs that take up Pf4 demonstrate defective migration and proliferation. Conclusions: Our findings are highly suggestive of Pf4 playing a role in the pathogenicity of Pa in the airways. These findings provide additional evidence for the ability of inoviruses to interact with mammalian cells and disrupt cell function. Full article
(This article belongs to the Special Issue Inoviruses)
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14 pages, 1821 KiB  
Article
Detection, Characterization and Sequencing of BTV Serotypes Circulating in Cuba in 2022
by Ana María Acevedo, Lydie Postic, Maray Curiel, Mathilde Gondard, Emmanuel Bréard, Stéphan Zientara, Fabien Vorimore, Mai-Lan Tran, Mathilde Turpaud, Giovanni Savini, Alessio Lorusso, Maurilia Marcacci, Damien Vitour, Pascal Dujardin, Carmen Laura Perera, Cristian Díaz, Yalainne Obret and Corinne Sailleau
Viruses 2024, 16(1), 164; https://doi.org/10.3390/v16010164 - 22 Jan 2024
Cited by 1 | Viewed by 1478
Abstract
In Cuba, despite a high sero-prevalence of bluetongue virus (BTV), circulating serotypes remain unknown. The aim of this study was to identify circulating BTV serotypes in farms throughout the western region of Cuba. Blood samples were collected from 200 young cattle and sheep [...] Read more.
In Cuba, despite a high sero-prevalence of bluetongue virus (BTV), circulating serotypes remain unknown. The aim of this study was to identify circulating BTV serotypes in farms throughout the western region of Cuba. Blood samples were collected from 200 young cattle and sheep between May and July 2022 for virological analyses (PCR, viral isolation and virus neutralization) and genome sequencing. The results confirmed viral circulation, with viro-prevalence of 25% for BTV. The virus was isolated from 18 blood samples and twelve BTV serotypes were identified by sequencing RT-PCR products targeting the segment 2 of the BTV genome (BTV-1, 2, 3, 6, 10, 12, 13, 17, 18, 19, 22 and 24). Finally, the full genome sequences of 17 Cuban BTV isolates were recovered using a Sequence Independent Single Primer Amplification (SISPA) approach combined to MinION Oxford Nanopore sequencing technology. All together, these results highlight the co-circulation of a wide diversity of BTV serotypes in a quite restricted area and emphasize the need for entomological and livestock surveillance, particularly in light of recent changes in the global distribution and nature of BTV infections. Full article
(This article belongs to the Special Issue Culicoides-Borne Viruses 2023)
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11 pages, 1366 KiB  
Article
The Chinese Hamster Ovary Cell-Based H9 HA Subunit Avian Influenza Vaccine Provides Complete Protection against the H9N2 Virus Challenge in Chickens
by Shunfan Zhu, Zhenyu Nie, Ying Che, Jianhong Shu, Sufang Wu, Yulong He, Youqiang Wu, Hong Qian, Huapeng Feng and Qiang Zhang
Viruses 2024, 16(1), 163; https://doi.org/10.3390/v16010163 - 22 Jan 2024
Cited by 2 | Viewed by 2010
Abstract
(1) Background: Avian influenza has attracted widespread attention because of its severe effect on the poultry industry and potential threat to human health. The H9N2 subtype of avian influenza viruses was the most prevalent in chickens, and there are several commercial vaccines available [...] Read more.
(1) Background: Avian influenza has attracted widespread attention because of its severe effect on the poultry industry and potential threat to human health. The H9N2 subtype of avian influenza viruses was the most prevalent in chickens, and there are several commercial vaccines available for the prevention of the H9N2 subtype of avian influenza viruses. However, due to the prompt antigenic drift and antigenic shift of influenza viruses, outbreaks of H9N2 viruses still continuously occur, so surveillance and vaccine updates for H9N2 subtype avian influenza viruses are particularly important. (2) Methods: In this study, we constructed a stable Chinese hamster ovary cell line (CHO) to express the H9 hemagglutinin (HA) protein of the major prevalent H9N2 strain A/chicken/Daye/DY0602/2017 with genetic engineering technology, and then a subunit H9 avian influenza vaccine was prepared using the purified HA protein with a water-in-oil adjuvant. (3) Results: The results showed that the HI antibodies significantly increased after vaccination with the H9 subunit vaccine in specific-pathogen-free (SPF) chickens with a dose–dependent potency of the immunized HA protein, and the 50 μg or more per dose HA protein could provide complete protection against the H9N2 virus challenge. (4) Conclusions: These results indicate that the CHO expression system could be a platform used to develop the subunit vaccine against H9 influenza viruses in chickens. Full article
(This article belongs to the Special Issue Advances in Animal Influenza Virus Research: Volume II)
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12 pages, 1926 KiB  
Article
Vaccine and Non-Vaccine HPV Types Presence in Adolescents with Vertically Acquired HIV Five Years Post Gardasil Quadrivalent Vaccination: The ZIMGARD Cohort
by Alltalents T. Murahwa, Tinashe Mudzviti, Racheal S. Dube Mandishora, Takudzwa Chatindo, Peace Chanetsa, Margaret Pascoe, Tinei Shamu, Wisdom Basera, Ruedi Luethy and Anna-Lise Williamson
Viruses 2024, 16(1), 162; https://doi.org/10.3390/v16010162 - 22 Jan 2024
Cited by 1 | Viewed by 2438
Abstract
Background: Human papillomavirus (HPV) vaccination programs are a key intervention in protecting individuals against HPV-related disease. HIV1-infected individuals are at increased risk of HPV-associated cancers. This study was conducted to evaluate the potential role of prophylactic HPV vaccines in preventing new HPV infections [...] Read more.
Background: Human papillomavirus (HPV) vaccination programs are a key intervention in protecting individuals against HPV-related disease. HIV1-infected individuals are at increased risk of HPV-associated cancers. This study was conducted to evaluate the potential role of prophylactic HPV vaccines in preventing new HPV infections among participants with perinatally acquired HIV who received the quadrivalent HPV vaccine at least five years before this study. Methods: This cross-sectional study was conducted at Newlands Clinic, Harare, Zimbabwe. The clinic provided the Gardasil quadrivalent HPV vaccine (4vHPV) to 624 adolescents living with HIV starting in December 2015. Vaginal and penile swabs were collected and tested for HPV types from the study participants who had received the 4vHPV vaccine 5–6 years before enrolment. Results: We present the results of 98 participants (44.6% female) vaccinated at a median age of 15 years (IQR 12–16). The mean amount of time since vaccination was 6 years (SD: ±0.4). The HPV-positive rate amongst the analyzed swabs was 69% (68/98). Among 30/98 (31%) HPV-positive participants, 13/98 (13%) had low-risk HPV types, and 17/98 (17%) had high-risk HPV types. Twelve participants tested positive for HPV18, only one participant tested positive for HPV16, and an additional four (4.3%) tested positive for either type 6 or 11, with respect to vaccine-preventable low-risk HPV types. Conclusion: The Gardasil quadrivalent HPV vaccine (4vHPV) was expected to protect against infection with HPV types 16, 18, 6, and 11. We demonstrated a possible waning of immunity to HPV18 in 17% of the participants, and an associated loss in cross-protection against HPV45. We observed a relatively high prevalence of ‘opportunistic non-vaccine HPV types’ or ‘ecological niche occupiers’ in this cohort, and suggest further research on the involvement of these types in cervical and other genital cancers. Our study is one of the few, if not the first, to report on HPV vaccine immunoprotection among people living with HIV (PLWH), thereby setting a baseline for further studies on HPV vaccine effectiveness among PLWH. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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15 pages, 2428 KiB  
Review
SARS-CoV-2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms
by Marília Inês Móvio, Giovana Waner Carneiro de Almeida, Isabella das Graças Lopes Martines, Gilmara Barros de Lima, Sergio Daishi Sasaki, Alexandre Hiroaki Kihara, Emma Poole, Michael Nevels and Maria Cristina Carlan da Silva
Viruses 2024, 16(1), 161; https://doi.org/10.3390/v16010161 - 22 Jan 2024
Cited by 3 | Viewed by 2337
Abstract
Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in lung damage, cardiovascular symptoms, hematologic symptoms, acute kidney injury and multiple organ failure that can lead to death. This remarkable increase in [...] Read more.
Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in lung damage, cardiovascular symptoms, hematologic symptoms, acute kidney injury and multiple organ failure that can lead to death. This remarkable increase in cytokines and other inflammatory molecules is primarily caused by viral proteins, and particular interest has been given to ORF8, a unique accessory protein specific to SARS-CoV-2. Despite plenty of research, the precise mechanisms by which ORF8 induces proinflammatory cytokines are not clear. Our investigations demonstrated that ORF8 augments production of IL-6 induced by Poly(I:C) in human embryonic kidney (HEK)-293 and monocyte-derived dendritic cells (mono-DCs). We discuss our findings and the multifaceted roles of ORF8 as a modulator of cytokine response, focusing on type I interferon and IL-6, a key component of the immune response to SARS-CoV-2. In addition, we explore the hypothesis that ORF8 may act through pattern recognition receptors of dsRNA such as TLRs. Full article
(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)
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10 pages, 664 KiB  
Review
Human Rabies Treatment—From Palliation to Promise
by Marian Lacy, Nonthapan Phasuk and Stephen J. Scholand
Viruses 2024, 16(1), 160; https://doi.org/10.3390/v16010160 - 22 Jan 2024
Cited by 2 | Viewed by 7398 | Correction
Abstract
Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has significantly reduced the burden of suffering and disease. However, around the world, rabies remains a neglected tropical disease, largely due to uncontrolled [...] Read more.
Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has significantly reduced the burden of suffering and disease. However, around the world, rabies remains a neglected tropical disease, largely due to uncontrolled dog rabies, and tens of thousands perish each year. Currently, the standard of care for management of rabies encephalitis is palliation. Heroic attempts to treat human rabies patients over the last few decades have yielded glimpses into our understanding of pathophysiology, opening the door to the development of new antiviral therapies and modalities of treatment. Researchers continue to investigate new compounds and approaches to therapy, yet there remain real challenges given the complexity of the disease. We explore and review some of the promising therapies on the horizon in pursuit of a salvage treatment for rabies. Full article
(This article belongs to the Special Issue Rabies Virus: Treatment and Prevention)
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18 pages, 3946 KiB  
Article
Genomic Expedition: Deciphering Human Adenovirus Strains from the 2023 Outbreak in West Bengal, India: Insights into Viral Evolution and Molecular Epidemiology
by Ananya Chatterjee, Uttaran Bhattacharjee, Rudrak Gupta, Ashis Debnath, Agniva Majumdar, Ritubrita Saha, Mamta Chawla-Sarkar, Alok Kumar Chakrabarti and Shanta Dutta
Viruses 2024, 16(1), 159; https://doi.org/10.3390/v16010159 - 21 Jan 2024
Cited by 1 | Viewed by 2086
Abstract
Understanding the genetic dynamics of circulating Human Adenovirus (HAdV) types is pivotal for effectively managing outbreaks and devising targeted interventions. During the West Bengal outbreak of 2022–2023, an investigation into the genetic characteristics and outbreak potential of circulating HAdV types was conducted. Twenty-four [...] Read more.
Understanding the genetic dynamics of circulating Human Adenovirus (HAdV) types is pivotal for effectively managing outbreaks and devising targeted interventions. During the West Bengal outbreak of 2022–2023, an investigation into the genetic characteristics and outbreak potential of circulating HAdV types was conducted. Twenty-four randomly selected samples underwent whole-genome sequencing. Analysis revealed a prevalent recombinant strain, merging type 3 and type 7 of human mastadenovirus B1 (HAd-B1) species, indicating the emergence of recent strains of species B in India. Furthermore, distinctions in VA-RNAs and the E3 region suggested that current circulating strains of human mastadenovirus B1 (HAd-B1) possess the capacity to evade host immunity, endure longer within hosts, and cause severe respiratory infections. This study underscores the significance of evaluating the complete genome sequence of HAdV isolates to glean insights into their outbreak potential and the severity of associated illnesses. Full article
(This article belongs to the Special Issue Population Genomics of Human Viruses)
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17 pages, 2495 KiB  
Article
The Global Evolutionary History of Orf Virus in Sheep and Goats Revealed by Whole Genomes Data
by Elisabetta Coradduzza, Fabio Scarpa, Angela Maria Rocchigiani, Carla Cacciotto, Giada Lostia, Mariangela Stefania Fiori, Yoel Rodriguez Valera, Alessandra Mistral De Pascali, Martina Brandolini, Ilenia Azzena, Chiara Locci, Marco Casu, Roberto Bechere, Davide Pintus, Ciriaco Ligios, Alessandra Scagliarini, Daria Sanna and Giantonella Puggioni
Viruses 2024, 16(1), 158; https://doi.org/10.3390/v16010158 - 21 Jan 2024
Cited by 1 | Viewed by 2137
Abstract
Orf virus (ORFV) belongs to the genus Parapoxvirus (Poxviridae family). It is the causative agent of contagious ecthyma (CE) that is an economically detrimental disease affecting small ruminants globally. Contagious ecthyma outbreaks are usually reported in intensive breeding of sheep and goats but [...] Read more.
Orf virus (ORFV) belongs to the genus Parapoxvirus (Poxviridae family). It is the causative agent of contagious ecthyma (CE) that is an economically detrimental disease affecting small ruminants globally. Contagious ecthyma outbreaks are usually reported in intensive breeding of sheep and goats but they have also been reported in wildlife species. Notably, ORFV can infect humans, leading to a zoonotic disease. This study aims to elucidate the global evolutionary history of ORFV genomes in sheep and goats, including the first genomes from Central America in the analyses. In comparison to the last study on ORFV whole genomes, the database now includes 11 more sheep and goat genomes, representing an increase of 42%. The analysis of such a broader database made it possible to obtain a fine molecular dating of the coalescent time for ORFV S and G genomes, further highlighting the genetic structuring between sheep and goat genomes and corroborating their emergence in the latter half of 20th century. Full article
(This article belongs to the Section Animal Viruses)
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13 pages, 1027 KiB  
Article
Molecular Survey on Porcine Parvoviruses (PPV1-7) and Their Association with Major Pathogens in Reproductive Failure Outbreaks in Northern Italy
by Giulia Faustini, Claudia Maria Tucciarone, Giovanni Franzo, Anna Donneschi, Maria Beatrice Boniotti, Giovanni Loris Alborali and Michele Drigo
Viruses 2024, 16(1), 157; https://doi.org/10.3390/v16010157 - 21 Jan 2024
Cited by 6 | Viewed by 1561
Abstract
Successful reproductive performance is key to farm competitiveness in the global marketplace. Porcine parvovirus 1 (PPV1) has been identified as a major cause of reproductive failure, and since 2001 new species of porcine parvoviruses, namely PPV2–7, have been identified, although their role is [...] Read more.
Successful reproductive performance is key to farm competitiveness in the global marketplace. Porcine parvovirus 1 (PPV1) has been identified as a major cause of reproductive failure, and since 2001 new species of porcine parvoviruses, namely PPV2–7, have been identified, although their role is not yet fully understood yet. The present study aimed to investigate PPVs’ presence in reproductive failure outbreaks occurring in 124 farms of northern Italy. Fetuses were collected from 338 sows between 2019 and 2021 and tested for PPVs by real-time PCR-based assays and for other viruses responsible for reproductive disease. At least one PPV species was detected in 59.7% (74/124) of the tested farms. In order, PPV1, PPV5, PPV6, PPV7 and PPV4 were the most frequently detected species, whereas fewer detections were registered for PPV2 and PPV3. Overall, the new PPV2–7 species were detected in 26.6% (90/338) of the cases, both alone or in co-infections: PCV-2 (7.1%, 24/338), PCV-3 (8.2%, 28/338), and PRRSV-1 (6.2%, 21/338) were frequently identified in association with PPVs. Single PPVs detections or co-infections with other agents commonly responsible for reproductive failure should encourage future studies investigating their biological, clinical, and epidemiological role, for a better preparedness for potential emerging challenges in intensive pig production. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2024)
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23 pages, 3441 KiB  
Review
Antivirals for Broader Coverage against Human Coronaviruses
by Mia Outteridge, Christine M. Nunn, Kevin Devine, Bhaven Patel and Gary R. McLean
Viruses 2024, 16(1), 156; https://doi.org/10.3390/v16010156 - 20 Jan 2024
Cited by 2 | Viewed by 2906
Abstract
Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses with a genome that is 27–31 kbases in length. Critical genes include the spike (S), envelope (E), membrane (M), nucleocapsid (N) and nine accessory open reading frames encoding for non-structural proteins (NSPs) that have multiple [...] Read more.
Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses with a genome that is 27–31 kbases in length. Critical genes include the spike (S), envelope (E), membrane (M), nucleocapsid (N) and nine accessory open reading frames encoding for non-structural proteins (NSPs) that have multiple roles in the replication cycle and immune evasion (1). There are seven known human CoVs that most likely appeared after zoonotic transfer, the most recent being SARS-CoV-2, responsible for the COVID-19 pandemic. Antivirals that have been approved by the FDA for use against COVID-19 such as Paxlovid can target and successfully inhibit the main protease (MPro) activity of multiple human CoVs; however, alternative proteomes encoded by CoV genomes have a closer genetic similarity to each other, suggesting that antivirals could be developed now that target future CoVs. New zoonotic introductions of CoVs to humans are inevitable and unpredictable. Therefore, new antivirals are required to control not only the next human CoV outbreak but also the four common human CoVs (229E, OC43, NL63, HKU1) that circulate frequently and to contain sporadic outbreaks of the severe human CoVs (SARS-CoV, MERS and SARS-CoV-2). The current study found that emerging antiviral drugs, such as Paxlovid, could target other CoVs, but only SARS-CoV-2 is known to be targeted in vivo. Other drugs which have the potential to target other human CoVs are still within clinical trials and are not yet available for public use. Monoclonal antibody (mAb) treatment and vaccines for SARS-CoV-2 can reduce mortality and hospitalisation rates; however, they target the Spike protein whose sequence mutates frequently and drifts. Spike is also not applicable for targeting other HCoVs as these are not well-conserved sequences among human CoVs. Thus, there is a need for readily available treatments globally that target all seven human CoVs and improve the preparedness for inevitable future outbreaks. Here, we discuss antiviral research, contributing to the control of common and severe CoV replication and transmission, including the current SARS-CoV-2 outbreak. The aim was to identify common features of CoVs for antivirals, biologics and vaccines that could reduce the scientific, political, economic and public health strain caused by CoV outbreaks now and in the future. Full article
(This article belongs to the Section Animal Viruses)
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21 pages, 3779 KiB  
Article
Color-Flu Fluorescent Reporter Influenza A Viruses Allow for In Vivo Studies of Innate Immune Function in Zebrafish
by Brandy-Lee Soos, Alec Ballinger, Mykayla Weinstein, Haley Foreman, Julianna Grampone, Samuel Weafer, Connor Aylesworth and Benjamin L. King
Viruses 2024, 16(1), 155; https://doi.org/10.3390/v16010155 - 20 Jan 2024
Cited by 1 | Viewed by 1867
Abstract
Influenza virus infection can cause severe respiratory disease and is estimated to cause millions of illnesses annually. Studies on the contribution of the innate immune response to influenza A virus (IAV) to viral pathogenesis may yield new antiviral strategies. Zebrafish larvae are useful [...] Read more.
Influenza virus infection can cause severe respiratory disease and is estimated to cause millions of illnesses annually. Studies on the contribution of the innate immune response to influenza A virus (IAV) to viral pathogenesis may yield new antiviral strategies. Zebrafish larvae are useful models for studying the innate immune response to pathogens, including IAV, in vivo. Here, we demonstrate how Color-flu, four fluorescent IAV strains originally developed for mice, can be used to study the host response to infection by simultaneously monitoring infected cells, neutrophils, and macrophages in vivo. Using this model, we show how the angiotensin-converting enzyme inhibitor, ramipril, and mitophagy inhibitor, MDIVI-1, improved survival, decreased viral burden, and improved the respiratory burst response to IAV infection. The Color-flu zebrafish larvae model of IAV infection is complementary to other models where the dynamics of infection and the response of innate immune cells can be visualized in a transparent host in vivo. Full article
(This article belongs to the Section Animal Viruses)
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12 pages, 2500 KiB  
Article
The Binding, Infection, and Promoted Growth of Batrachochytrium dendrobatidis by the Ranavirus FV3
by Francisco De Jesús Andino, Anton Davydenko, Rebecca J. Webb and Jacques Robert
Viruses 2024, 16(1), 154; https://doi.org/10.3390/v16010154 - 20 Jan 2024
Cited by 1 | Viewed by 2565
Abstract
Increasing reports suggest the occurrence of co-infection between Ranaviruses such as Frog Virus 3 (FV3) and the chytrid fungus Batrachochytrium dendrobatidis (Bd) in various amphibian species. However, the potential direct interaction of these two pathogens has not been examined to date. In this [...] Read more.
Increasing reports suggest the occurrence of co-infection between Ranaviruses such as Frog Virus 3 (FV3) and the chytrid fungus Batrachochytrium dendrobatidis (Bd) in various amphibian species. However, the potential direct interaction of these two pathogens has not been examined to date. In this study, we investigated whether FV3 can interact with Bd in vitro using qPCR, conventional microscopy, and immunofluorescent microscopy. Our results reveal the unexpected ability of FV3 to bind, promote aggregation, productively infect, and significantly increase Bd growth in vitro. To extend these results in vivo, we assessed the impact of FV3 on Xenopus tropicalis frogs previously infected with Bd. Consistent with in vitro results, FV3 exposure to previously Bd-infected X. tropicalis significantly increased Bd loads and decreased the host’s survival. Full article
(This article belongs to the Special Issue Iridoviruses)
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12 pages, 1482 KiB  
Article
Optimizing Vaccination Strategies against African Swine Fever Using Spatial Data from Wild Boars in Lithuania
by Vincenzo Gervasi, Marius Masiulis, Paulius Bušauskas, Silvia Bellini and Vittorio Guberti
Viruses 2024, 16(1), 153; https://doi.org/10.3390/v16010153 - 19 Jan 2024
Cited by 1 | Viewed by 1415
Abstract
African swine fever (ASF) is one of the most severe suid diseases, impacting the pig industry and wild suid populations. Once an ASF vaccine is available, identifying a sufficient density of vaccination fields will be crucial to achieve eradication success. In 2020–2023, we [...] Read more.
African swine fever (ASF) is one of the most severe suid diseases, impacting the pig industry and wild suid populations. Once an ASF vaccine is available, identifying a sufficient density of vaccination fields will be crucial to achieve eradication success. In 2020–2023, we live-trapped and monitored 27 wild boars in different areas of Lithuania, in which the wild boars were fed at artificial stations. We built a simulation study to estimate the probability of a successful ASF vaccination as a function of different eco-epidemiological factors. The average 32-day home range size across all individuals was 16.2 km2 (SD = 16.9). The wild boars made frequent visits of short durations to the feeding sites rather than long visits interposed by long periods of absence. A feeding site density of 0.5/km2 corresponded to an expected vaccination rate of only 20%. The vaccination probability increased to about 75% when the feeding site density was 1.0/km2. Our results suggest that at least one vaccination field/km2 should be used when planning an ASF vaccination campaign to ensure that everyone in the population has at least 5–10 vaccination sites available inside the home range. Similar studies should be conducted in the other ecological contexts in which ASF is present today or will be present in the future, with the objective being to estimate a context-specific relationship between wild boar movement patterns and an optimal vaccination strategy. Full article
(This article belongs to the Special Issue African Swine Fever Virus 4.0)
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15 pages, 1398 KiB  
Article
Probenecid Inhibits Influenza A(H5N1) and A(H7N9) Viruses In Vitro and in Mice
by Jackelyn Murray, David E. Martin, Sarah Hosking, Nichole Orr-Burks, Robert J. Hogan and Ralph A. Tripp
Viruses 2024, 16(1), 152; https://doi.org/10.3390/v16010152 - 19 Jan 2024
Cited by 2 | Viewed by 1786
Abstract
Avian influenza (AI) viruses cause infection in birds and humans. Several H5N1 and H7N9 variants are highly pathogenic avian influenza (HPAI) viruses. H5N1 is a highly infectious bird virus infecting primarily poultry, but unlike other AIs, H5N1 also infects mammals and transmits to [...] Read more.
Avian influenza (AI) viruses cause infection in birds and humans. Several H5N1 and H7N9 variants are highly pathogenic avian influenza (HPAI) viruses. H5N1 is a highly infectious bird virus infecting primarily poultry, but unlike other AIs, H5N1 also infects mammals and transmits to humans with a case fatality rate above 40%. Similarly, H7N9 can infect humans, with a case fatality rate of over 40%. Since 1996, there have been several HPAI outbreaks affecting humans, emphasizing the need for safe and effective antivirals. We show that probenecid potently inhibits H5N1 and H7N9 replication in prophylactically or therapeutically treated A549 cells and normal human broncho-epithelial (NHBE) cells, and H5N1 replication in VeroE6 cells and mice. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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13 pages, 247 KiB  
Review
Aerosol Transmission of Norovirus
by Mengdi Tan, Yi Tian, Daitao Zhang, Quanyi Wang and Zhiyong Gao
Viruses 2024, 16(1), 151; https://doi.org/10.3390/v16010151 - 19 Jan 2024
Cited by 4 | Viewed by 3028
Abstract
Norovirus (NoV) is a major cause of acute gastroenteritis outbreaks worldwide. A comprehensive understanding of the transmission mode is of great significance for the prevention and control of the NoV infection. Currently, the transmission modes of NoV include contact, food-borne, water-borne and aerosol [...] Read more.
Norovirus (NoV) is a major cause of acute gastroenteritis outbreaks worldwide. A comprehensive understanding of the transmission mode is of great significance for the prevention and control of the NoV infection. Currently, the transmission modes of NoV include contact, food-borne, water-borne and aerosol transmission. The first three modes are more common, while aerosol transmission is seldom reported. In this paper, the source, generation mechanism, infectivity, sampling and related outbreaks of NoV aerosol are summarized and discussed. Full article
(This article belongs to the Section General Virology)
10 pages, 828 KiB  
Case Report
Genomic Characterization of a Wild-Type Bovine alphaherpesvirus 1 (BoAHV-1) Strain Isolated in an Outbreak in Central Italy
by Stefano Petrini, Valentina Curini, Cecilia Righi, Cesare Cammà, Valeria Di Lollo, Elena Tinelli, Luana Fiorella Mincarelli, Elisabetta Rossi, Giulia Costantino, Barbara Secondini, Silvia Pirani, Monica Giammarioli and Francesco Feliziani
Viruses 2024, 16(1), 150; https://doi.org/10.3390/v16010150 - 19 Jan 2024
Cited by 1 | Viewed by 1817
Abstract
Bovine alphaherpesvirus-1 (BoAHV-1) infection is common in cattle worldwide. However, information on the spread of BoAHV-1-circulating strains in Italy remains limited. In this study, we investigated an outbreak characterized by severe respiratory symptoms in a cattle herd (n = 30) located in [...] Read more.
Bovine alphaherpesvirus-1 (BoAHV-1) infection is common in cattle worldwide. However, information on the spread of BoAHV-1-circulating strains in Italy remains limited. In this study, we investigated an outbreak characterized by severe respiratory symptoms in a cattle herd (n = 30) located in Central Italy. BoAHV-1 was isolated from three cattle in a cell culture, which confirmed viral infection. Next, we characterized one (16453/07 TN) of the three isolates of BoAHV-1 using whole-genome sequencing. BLASTn and phylogenetic analysis revealed a nucleotide identity >99% with all BoAHV-1 strains belonging to subtype 1.1, highlighting the genetic stability of the virus. This study reports the first full genomic characterization of a BoAHV-1 isolate in Italy, enriching our understanding of the genetic characteristics of the circulating BoAHV-1 strain in Italy. Full article
(This article belongs to the Section Animal Viruses)
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1 pages, 140 KiB  
Reply
Reply to Piewbang et al. Domestic Cat Hepadnavirus Antigens in Lymphoma Tissues. Comment on “Beatty et al. Domestic Cat Hepadnavirus and Lymphoma. Viruses 2023, 15, 2294”
by Julia A. Beatty, Thomas Tu, Patricia A. Pesavento, Joao P. Cavasin, Min-Chun Chen, Jonathan A. Lidbury, Joerg M. Steiner, Vanessa R. Barrs and John M. Cullen
Viruses 2024, 16(1), 149; https://doi.org/10.3390/v16010149 - 19 Jan 2024
Cited by 1 | Viewed by 940
Abstract
We are grateful to the authors for providing additional data to demonstrate the presence of domestic cat hepadnavirus in lymphoma tissues [...] Full article
(This article belongs to the Section Animal Viruses)
5 pages, 975 KiB  
Comment
Domestic Cat Hepadnavirus Antigens in Lymphoma Tissues. Comment on Beatty et al. Domestic Cat Hepadnavirus and Lymphoma. Viruses 2023, 15, 2294
by Chutchai Piewbang, Sabrina Wahyu Wardhani, Jedsada Siripoonsub, Sirintra Sirivisoot, Anudep Rungsipipat and Somporn Techangamsuwan
Viruses 2024, 16(1), 148; https://doi.org/10.3390/v16010148 - 19 Jan 2024
Cited by 1 | Viewed by 1260
Abstract
We are addressing the comments made by Beatty et al [...] Full article
(This article belongs to the Section Animal Viruses)
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20 pages, 3218 KiB  
Article
Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence
by Yoandry Hinojosa, Matthias Liniger, Obdulio García-Nicolás, Markus Gerber, Anojen Rajaratnam, Sara Muñoz-González, Liani Coronado, María Teresa Frías, Carmen Laura Perera, Llilianne Ganges and Nicolas Ruggli
Viruses 2024, 16(1), 147; https://doi.org/10.3390/v16010147 - 19 Jan 2024
Viewed by 1607
Abstract
Classical swine fever (CSF) has been eradicated from Western and Central Europe but remains endemic in parts of Central and South America, Asia, and the Caribbean. CSF virus (CSFV) has been endemic in Cuba since 1993, most likely following an escape of the [...] Read more.
Classical swine fever (CSF) has been eradicated from Western and Central Europe but remains endemic in parts of Central and South America, Asia, and the Caribbean. CSF virus (CSFV) has been endemic in Cuba since 1993, most likely following an escape of the highly virulent Margarita/1958 strain. In recent years, chronic and persistent infections with low-virulent CSFV have been observed. Amino acid substitutions located in immunodominant epitopes of the envelope glycoprotein E2 of the attenuated isolates were attributed to positive selection due to suboptimal vaccination and control. To obtain a complete picture of the mutations involved in attenuation, we applied forward and reverse genetics using the evolutionary-related low-virulent CSFV/Pinar del Rio (CSF1058)/2010 (PdR) and highly virulent Margarita/1958 isolates. Sequence comparison of the two viruses recovered from experimental infections in pigs revealed 40 amino acid differences. Interestingly, the amino acid substitutions clustered in E2 and the NS5A and NS5B proteins. A long poly-uridine sequence was identified previously in the 3′ untranslated region (UTR) of PdR. We constructed functional cDNA clones of the PdR and Margarita strains and generated eight recombinant viruses by introducing single or multiple gene fragments from Margarita into the PdR backbone. All chimeric viruses had comparable replication characteristics in porcine monocyte-derived macrophages. Recombinant PdR viruses carrying either E2 or NS5A/NS5B of Margarita, with 36 or 5 uridines in the 3′UTR, remained low virulent in 3-month-old pigs. The combination of these elements recovered the high-virulent Margarita phenotype. These results show that CSFV evolution towards attenuated variants in the field involved mutations in both structural and non-structural proteins and the UTRs, which act synergistically to determine virulence. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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13 pages, 2599 KiB  
Article
Genomic Characterization and Molecular Evolution of Sapovirus in Children under 5 Years of Age
by Xiaolei Ji, Chen Guo, Yaoyao Dai, Lu Chen, Yujia Chen, Shifang Wang and Yihua Sun
Viruses 2024, 16(1), 146; https://doi.org/10.3390/v16010146 - 19 Jan 2024
Cited by 1 | Viewed by 1389
Abstract
Sapovirus (SaV) is a type of gastroenteric virus that can cause acute gastroenteritis. It is highly contagious, particularly among children under the age of 5. In this study, a total of 712 stool samples from children under the age of 5 with acute [...] Read more.
Sapovirus (SaV) is a type of gastroenteric virus that can cause acute gastroenteritis. It is highly contagious, particularly among children under the age of 5. In this study, a total of 712 stool samples from children under the age of 5 with acute gastroenteritis were collected. Out of these samples, 28 tested positive for SaV, resulting in a detection rate of 3.93% (28/712). Samples with Ct < 30 were collected for library construction and high-throughput sequencing, resulting in the acquisition of nine complete genomes. According to Blast, eight of them were identified as GI.1, while the remaining one was GI.6. The GI.6 strain sequence reported in our study represents the first submission of the GI.6 strain complete genome sequence from mainland China to the Genbank database, thus filling the data gap in our country. Sequence identity analysis revealed significant nucleotide variations between the two genotypes of SaV and their corresponding prototype strains. Phylogenetic and genetic evolution analyses showed no evidence of recombination events in the obtained sequences. Population dynamics analysis demonstrated potential competitive inhibition between two lineages of GI.1. Our study provides insights into the molecular epidemiological and genetic evolution characteristics of SaV prevalent in the Nantong region of China, laying the foundation for disease prevention and control, as well as pathogen tracing related to SaV in this area. Full article
(This article belongs to the Special Issue Caliciviruses)
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14 pages, 4757 KiB  
Article
Epidemiology of Hemorrhagic Fever with Renal Syndrome and Host Surveillance in Zhejiang Province, China, 1990–2021
by Fan Su, Ying Liu, Feng Ling, Rong Zhang, Zhen Wang and Jimin Sun
Viruses 2024, 16(1), 145; https://doi.org/10.3390/v16010145 - 19 Jan 2024
Cited by 1 | Viewed by 1465
Abstract
Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses (HVs) and is endemic in Zhejiang Province, China. In this study, we aimed to explore the changing epidemiology of HFRS cases and the dynamics of hantavirus hosts in Zhejiang Province. Joinpoint regression was [...] Read more.
Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses (HVs) and is endemic in Zhejiang Province, China. In this study, we aimed to explore the changing epidemiology of HFRS cases and the dynamics of hantavirus hosts in Zhejiang Province. Joinpoint regression was used to analyze long-term trends in the incidence of HFRS. The comparison of animal density at different stages was conducted using the Mann–Whitney Test. A comparison of HV carriage rates between stages and species was performed using the chi-square test. The incidence of HFRS shows a continuous downward trend. Cases are widely distributed in all counties of Zhejiang Province except Shengsi County. There was a high incidence belt from west to east, with low incidence in the south and north. The HFRS epidemic showed two seasonal peaks in Zhejiang Province, which were winter and summer. It showed a marked increase in the age of the incidence population. A total of 23,073 minibeasts from 21 species were captured. Positive results were detected in the lung tissues of 14 rodent species and 1 shrew species. A total of 80% of the positive results were from striped field mice and brown rats. No difference in HV carriage rates between striped field mice and brown rats was observed (χ2 = 0.258, p = 0.611). Full article
(This article belongs to the Special Issue Vectors for Insect Viruses)
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49 pages, 5370 KiB  
Review
Australian Cool-Season Pulse Seed-Borne Virus Research: 1. Alfalfa and Cucumber Mosaic Viruses and Less Important Viruses
by Roger A. C. Jones and Benjamin S. Congdon
Viruses 2024, 16(1), 144; https://doi.org/10.3390/v16010144 - 18 Jan 2024
Cited by 2 | Viewed by 1739
Abstract
Here, we review the research undertaken since the 1950s in Australia’s grain cropping regions on seed-borne virus diseases of cool-season pulses caused by alfalfa mosaic virus (AMV) and cucumber mosaic virus (CMV). We present brief background information about the continent’s pulse industry, virus [...] Read more.
Here, we review the research undertaken since the 1950s in Australia’s grain cropping regions on seed-borne virus diseases of cool-season pulses caused by alfalfa mosaic virus (AMV) and cucumber mosaic virus (CMV). We present brief background information about the continent’s pulse industry, virus epidemiology, management principles and future threats to virus disease management. We then take a historical approach towards all past investigations with these two seed-borne pulse viruses in the principal cool-season pulse crops grown: chickpea, faba bean, field pea, lentil, narrow-leafed lupin and white lupin. With each pathosystem, the main focus is on its biology, epidemiology and management, placing particular emphasis on describing field and glasshouse experimentation that enabled the development of effective phytosanitary, cultural and host resistance control strategies. Past Australian cool-season pulse investigations with AMV and CMV in the less commonly grown species (vetches, narbon bean, fenugreek, yellow and pearl lupin, grass pea and other Lathyrus species) and those with the five less important seed-borne pulse viruses also found (broad bean stain virus, broad bean true mosaic virus, broad bean wilt virus, cowpea mild mottle virus and peanut mottle virus) are also summarized. The need for future research is emphasized, and recommendations are made regarding what is required. Full article
(This article belongs to the Special Issue Plant Virus Epidemiology and Control 2023)
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13 pages, 848 KiB  
Article
High-Density Lipoprotein Particles and Torque Teno Virus in Stable Outpatient Kidney Transplant Recipients
by Jip Jonker, Caecilia S. E. Doorenbos, Daan Kremer, Edmund J. Gore, Hubert G. M. Niesters, Coretta van Leer-Buter, Philippe Bourgeois, Margery A. Connelly, Robin P. F. Dullaart, Stefan P. Berger, Jan-Stephan F. Sanders and Stephan J. L. Bakker
Viruses 2024, 16(1), 143; https://doi.org/10.3390/v16010143 - 18 Jan 2024
Cited by 1 | Viewed by 1630
Abstract
Torque teno virus (TTV) is emerging as a potential marker for monitoring immune status. In transplant recipients who are immunosuppressed, higher TTV DNA loads are observed than in healthy individuals. TTV load measurement may aid in optimizing immunosuppressive medication dosing in solid organ [...] Read more.
Torque teno virus (TTV) is emerging as a potential marker for monitoring immune status. In transplant recipients who are immunosuppressed, higher TTV DNA loads are observed than in healthy individuals. TTV load measurement may aid in optimizing immunosuppressive medication dosing in solid organ transplant recipients. Additionally, there is a growing interest in the role of HDL particles in immune function; therefore, assessment of both HDL concentrations and TTV load may be of interest in transplant recipients. The objective of this study was to analyze TTV loads and HDL parameters in serum samples collected at least one year post-transplantation from 656 stable outpatient kidney transplant recipients (KTRs), enrolled in the TransplantLines Food and Nutrition Cohort (Groningen, the Netherlands). Plasma HDL particles and subfractions were measured using nuclear magnetic resonance spectroscopy. Serum TTV load was measured using a quantitative real-time polymerase chain reaction. Associations between HDL parameters and TTV load were examined using univariable and multivariable linear regression. The median age was 54.6 [IQR: 44.6 to 63.1] years, 43.3% were female, the mean eGFR was 52.5 (±20.6) mL/min/1.73 m2 and the median allograft vintage was 5.4 [IQR: 2.0 to 12.0] years. A total of 539 participants (82.2%) had a detectable TTV load with a mean TTV load of 3.04 (±1.53) log10 copies/mL, the mean total HDL particle concentration was 19.7 (±3.4) μmol/L, and the mean HDL size was 9.1 (±0.5) nm. The univariable linear regression revealed a negative association between total HDL particle concentration and TTV load (st.β = −0.17, 95% CI st.β: −0.26 to −0.09, p < 0.001). An effect modification of smoking behavior influencing the association between HDL particle concentration and TTV load was observed (Pinteraction = 0.024). After adjustment for age, sex, alcohol intake, hemoglobin, eGFR, donor age, allograft vintage and the use of calcineurin inhibitors, the negative association between HDL particle concentration and TTV load remained statistically significant in the non-smoking population (st.β = −0.14, 95% CI st.β: −0.23 to −0.04, p = 0.006). Furthermore, an association between small HDL particle concentration and TTV load was found (st.β = −0.12, 95% CI st.β: −0.22 to −0.02, p = 0.017). Higher HDL particle concentrations were associated with a lower TTV load in kidney transplant recipients, potentially indicative of a higher immune function. Interventional studies are needed to provide causal evidence on the effects of HDL on the immune system. Full article
(This article belongs to the Special Issue Advancing Research of Anelloviruses)
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11 pages, 3689 KiB  
Systematic Review
Prevention of Viral Hepatitis and HIV Infection among People Who Inject Drugs: A Systematic Review and Meta-Analysis
by Yen-Ju Chen, Yu-Chen Lin, Meng-Tien Wu, Jenn-Yuan Kuo and Chun-Hsiang Wang
Viruses 2024, 16(1), 142; https://doi.org/10.3390/v16010142 - 18 Jan 2024
Cited by 2 | Viewed by 1898
Abstract
This study aimed to explore the current evidence on preventing blood-borne virus infections among people who inject drugs (PWID). We conducted a comprehensive search across three databases (PubMed, Embase, Cochrane Library) for relevant articles published in English between 2014 and 2023. We followed [...] Read more.
This study aimed to explore the current evidence on preventing blood-borne virus infections among people who inject drugs (PWID). We conducted a comprehensive search across three databases (PubMed, Embase, Cochrane Library) for relevant articles published in English between 2014 and 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines, assessed the quality of the paper using the revised Cochrane Risk of Bias Tool (ROB 2), and conducted a meta-analysis using RevMan 5.3. Completing the harm reduction program (HRP) participation and receiving all three vaccine doses resulted in a 28% reduction in the risk of HBV infection (OR: 0.72, 95% CI: 0.37–1.42). Various interventions increased the willingness of PWIDs to undergo HCV treatment (OR: 5.91, 95% CI: 2.46–14.24) and promoted treatment adherence (OR: 15.04, 95% CI: 2.80–80.61). Taking PrEP, participating in HRP, and modifying risky behaviors were associated with a 33% reduction in the risk of HIV infection (OR: 0.67, 95% CI: 0.61–0.74). Conducting referrals, providing counseling, and implementing antiretroviral therapy resulted in a 44% reduction in the risk of viral transmission (OR: 0.56, 95% CI: 0.47–0.66). Co-infection may potentially compromise effectiveness, so it is important to consider drug resistance. Full article
(This article belongs to the Special Issue Ways to Eliminate Viral Hepatitis as a Global Health Threat 2.0)
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18 pages, 1375 KiB  
Article
An Aptamer-Based Proteomic Analysis of Plasma from Cats (Felis catus) with Clinical Feline Infectious Peritonitis
by Benjamin E. Curtis, Zaid Abdo, Barbara Graham, Alora LaVoy, Samantha J. M. Evans, Kelly Santangelo and Gregg A. Dean
Viruses 2024, 16(1), 141; https://doi.org/10.3390/v16010141 - 18 Jan 2024
Viewed by 1739
Abstract
Feline infectious peritonitis (FIP) is a systemic disease manifestation of feline coronavirus (FCoV) and is the most important cause of infectious disease-related deaths in domestic cats. FIP has a variable clinical manifestation but is most often characterized by widespread vasculitis with visceral involvement [...] Read more.
Feline infectious peritonitis (FIP) is a systemic disease manifestation of feline coronavirus (FCoV) and is the most important cause of infectious disease-related deaths in domestic cats. FIP has a variable clinical manifestation but is most often characterized by widespread vasculitis with visceral involvement and/or neurological disease that is typically fatal in the absence of antiviral therapy. Using an aptamer-based proteomics assay, we analyzed the plasma protein profiles of cats who were naturally infected with FIP (n = 19) in comparison to the plasma protein profiles of cats who were clinically healthy and negative for FCoV (n = 17) and cats who were positive for the enteric form of FCoV (n = 9). We identified 442 proteins that were significantly differentiable; in total, 219 increased and 223 decreased in FIP plasma versus clinically healthy cat plasma. Pathway enrichment and associated analyses showed that differentiable proteins were related to immune system processes, including the innate immune response, cytokine signaling, and antigen presentation, as well as apoptosis and vascular integrity. The relevance of these findings is discussed in the context of previous studies. While these results have the potential to inform diagnostic, therapeutic, and preventative investigations, they represent only a first step, and will require further validation. Full article
(This article belongs to the Special Issue Viral Infections in Companion Animals: Volume 2)
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14 pages, 6053 KiB  
Article
Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK
by Justin H. Franco, Ryan A. Harris, William G. Ryan, Roger Travis Taylor, Robert E. McCullumsmith, Saurabh Chattopadhyay and Zhixing K. Pan
Viruses 2024, 16(1), 140; https://doi.org/10.3390/v16010140 - 18 Jan 2024
Cited by 1 | Viewed by 1724
Abstract
The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic [...] Read more.
The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling pathways, RA’s mechanism of action during coronavirus infection has not been thoroughly described. To determine RA’s mechanism of action, we examined its effect against a mouse coronavirus, mouse hepatitis virus strain A59 (MHV). We demonstrated that RA significantly decreased viral titers in infected mouse L929 fibroblasts and RAW 264.7 macrophages. The reduced viral titers were associated with a corresponding decrease in MHV nucleocapsid protein expression. Using interferon regulatory factor 3 (IRF3) knockout RAW 264.7 cells, we demonstrated that RA-induced suppression of MHV required IRF3 activity. RNA-seq analysis of wildtype and IRF3 knockout RAW cells showed that RA upregulated calcium/calmodulin (CaM) signaling proteins, such as CaM kinase kinase 1 (CaMKK1). When treated with a CaMKK inhibitor, RA was unable to upregulate IRF activation during MHV infection. In conclusion, our results demonstrate that RA-induced protection against coronavirus infection depends on IRF3 and CaMKK. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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4 pages, 174 KiB  
Editorial
What SARS-CoV-2 Variants Have Taught Us: Evolutionary Challenges of RNA Viruses
by Shymaa E. Bilasy, Tutik Sri Wahyuni, Mohamed Ibrahim and Ahmed El-Shamy
Viruses 2024, 16(1), 139; https://doi.org/10.3390/v16010139 - 18 Jan 2024
Viewed by 1148
Abstract
Since its discovery in 2019, SARS-CoV-2 still makes the headline news [...] Full article
(This article belongs to the Special Issue What SARS-CoV-2 Variants Have Taught Us: Evolutionary Challenges of RNA Viruses)
14 pages, 1349 KiB  
Article
Genomic Analyses Uncover Evolutionary Features of Influenza A/H3N2 Viruses in Yunnan Province, China, from 2017 to 2022
by Meiling Zhang, Jienan Zhou, Ruize Ni, Xiaonan Zhao, Yaoyao Chen, Yanhong Sun, Zhaosheng Liu, Xiaoyu Han, Chunrui Luo, Xiaoqing Fu and Yong Shao
Viruses 2024, 16(1), 138; https://doi.org/10.3390/v16010138 - 18 Jan 2024
Cited by 1 | Viewed by 1604
Abstract
Influenza A viruses evolve at a high rate of nucleotide substitution, thereby requiring continuous monitoring to determine the efficacy of vaccines and antiviral drugs. In the current study, we performed whole-genome sequencing analyses of 253 influenza A/H3N2 strains from Yunnan Province, China, during [...] Read more.
Influenza A viruses evolve at a high rate of nucleotide substitution, thereby requiring continuous monitoring to determine the efficacy of vaccines and antiviral drugs. In the current study, we performed whole-genome sequencing analyses of 253 influenza A/H3N2 strains from Yunnan Province, China, during 2017–2022. The hemagglutinin (HA) segments of Yunnan A/H3N2 strains isolated during 2017–2018 harbored a high genetic diversity due to heterogeneous distribution across branches. The mutation regularity of the predominant antigenic epitopes of HA segments in Yunnan was inconsistent in different years. Some important functional mutations in gene segments associated with viral adaptation and drug tolerance were revealed. The rapid genomic evolution of Yunnan A/H3N2 strains from 2017 to 2022 mainly concentrated on segments, i.e., matrix protein 2 (M2), non-structural protein 1 (NS1), neuraminidase (NA), NS2, and HA, with a high overall non-synonymous/synonymous substitution ratio (dN/dS). Our results highlighted a decline in vaccine efficacy against the A/H3N2 circulating strains, particularly against the Yunnan 2021–2022 A/H3N2 strains. These findings aid our understanding of evolutionary characteristics and epidemiological monitoring of the A/H3N2 viruses and provide in-depth insights into the protective efficacy of influenza vaccines. Full article
(This article belongs to the Section Animal Viruses)
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13 pages, 2962 KiB  
Article
A Fulminant Case of Adenovirus Genotype C108 Infection in a Pediatric Stem Cell Transplant Recipient with x-Linked Lymphoproliferative Syndrome Type 1
by Bradford A. Becken, Daryl M. Lamson, Gabriel Gonzalez, Sachit Patel, Kirsten St. George and Adriana E. Kajon
Viruses 2024, 16(1), 137; https://doi.org/10.3390/v16010137 - 18 Jan 2024
Viewed by 1570
Abstract
A 3-year-old male with X-linked lymphoproliferative syndrome type 1 underwent an unrelated umbilical cord blood transplant (UUCBT). The week prior to transplant the patient tested positive for adenovirus (HAdV) with a viral load of <190 copies/mL and was started on cidofovir. UUCBT proceeded [...] Read more.
A 3-year-old male with X-linked lymphoproliferative syndrome type 1 underwent an unrelated umbilical cord blood transplant (UUCBT). The week prior to transplant the patient tested positive for adenovirus (HAdV) with a viral load of <190 copies/mL and was started on cidofovir. UUCBT proceeded as scheduled, and the patient engrafted on day +19. The patient’s HAdV load in serum continued to rise with resulting hepatic dysfunction, despite ongoing therapy with cidofovir and HAdV specific T-cell infusions. The patient died 6 months after transplantation having never cleared the virus. Next generation whole genome sequencing and sequence data analyses identified an intertypic recombinant HAdV-C P1H2F2 closely related (99.6% similarity) to genotype C108 in the isolates from three blood specimens obtained during the last week of life. Incidentally, the de novo assembly strategy enabled the detection of an adeno-associated virus type 2 (AAV2) genome in the DNA purified from the plasma isolates. Proteotyping analysis revealed minor differences in the predicted amino acid sequences for E1A, E1B 19K, E1B 55K, DNA polymerase, penton base, and fiber. None of the mutations previously described for HAdV-C5 variants resistant to cidofovir were identified. In silico restriction enzyme analysis revealed a distinct Sac I profile for the identified virus, supporting its designation as a C108 variant. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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