Viruses

7 pages, 214 KiB

Open AccessArticle

High Levels of Incidental COVID-19 Infection in Emergency Urology Admissions: A Propensity Score-Matched Real World Data Analysis across Surgical Specialties

by Alex Qinyang Liu, Eric Ka-Ho Choy, Peter Ka-Fung Chiu, Chi-Hang Yee, Chi-Fai Ng and Jeremy Yuen-Chun Teoh

Viruses 2024, 16(9), 1402; https://doi.org/10.3390/v16091402 (registering DOI) - 31 Aug 2024

Abstract

Background: An incidental COVID-19 infection is often found in patients admitted for non-COVID-19-related conditions. This study aims to investigate the incidence of COVID-19 infections across surgical specialties including urology, general surgery, and orthopaedic surgery. Methods: This is a retrospective cohort study based on [...] Read more.

Background: An incidental COVID-19 infection is often found in patients admitted for non-COVID-19-related conditions. This study aims to investigate the incidence of COVID-19 infections across surgical specialties including urology, general surgery, and orthopaedic surgery. Methods: This is a retrospective cohort study based on a territory-wide electronic database in Hong Kong. All emergency in-hospital admissions under the urology, general surgery, and orthopaedic surgery divisions in the public healthcare system in Hong Kong from January to September 2022 were included. All patients were routinely screened for SARS-CoV-2, based on admission protocols during the investigation period. Baseline characteristics were retrieved, with 1:1:1 propensity score matching being performed. Incidental COVID-19 rates were then compared across specialties. Results: A total of 126,034 patients were included. After propensity score matching, the baseline characteristics were well balanced, and 8535 patients in each group were analysed. Urology admission was noted to have a statistically significant higher incidence of incidental COVID-19 at 9.3%, compared to general surgery (5.4%) or orthopaedic surgery (5.6%). Amongst urology patients with incidental COVID-19 infection, 35.8% were admitted for retention of urine, 27.9% for haematuria, and 8.6% for a urinary tract infection. Conclusions: This large-scale cohort study demonstrated that incidental COVID-19 rates differ between surgical specialties, with urology having the highest proportion of incidental COVID-19 infection. Full article

(This article belongs to the Special Issue COVID-19 Complications and Co-infections)

10 pages, 3633 KiB

Open AccessCommunication

Resistance of the CRISPR-Cas13a Gene-Editing System to Potato Spindle Tuber Viroid Infection in Tomato and Nicotiana benthamiana

by Ying Wei Khoo, Qingsong Wang, Shangwu Liu, Binhui Zhan, Tengfei Xu, Wenxia Lv, Guangjing Liu, Shifang Li and Zhixiang Zhang

Viruses 2024, 16(9), 1401; https://doi.org/10.3390/v16091401 (registering DOI) - 31 Aug 2024

Abstract

Gene-editing technology, specifically the CRISPR-Cas13a system, has shown promise in breeding plants resistant to RNA viruses. This system targets RNA and, theoretically, can also combat RNA-based viroids. To test this, the CRISPR-Cas13a system was introduced into tomato plants via transient expression and into [...] Read more.

Gene-editing technology, specifically the CRISPR-Cas13a system, has shown promise in breeding plants resistant to RNA viruses. This system targets RNA and, theoretically, can also combat RNA-based viroids. To test this, the CRISPR-Cas13a system was introduced into tomato plants via transient expression and into Nicotiana benthamiana through transgenic methods, using CRISPR RNAs (crRNAs) targeting the conserved regions of both sense and antisense genomes of potato spindle tuber viroid (PSTVd). In tomato plants, the expression of CRISPR-Cas13a and crRNAs substantially reduced PSTVd accumulation and alleviated disease symptoms. In transgenic N. benthamiana plants, the PSTVd levels were lower as compared to wild-type plants. Several effective crRNAs targeting the PSTVd genomic RNA were also identified. These results demonstrate that the CRISPR-Cas13a system can effectively target and combat viroid RNAs, despite their compact structures. Full article

(This article belongs to the Special Issue Crop Resistance to Viral Infections)

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21 pages, 13118 KiB

Open AccessArticle

Production and Characterization of Self-Assembled Virus-like Particles Comprising Capsid Proteins from Genotypes 3 and 4 Hepatitis E Virus (HEV) and Rabbit HEV Expressed in Escherichia coli

by Tominari Kobayashi, Masaharu Takahashi, Satoshi Ohta, Yu Hoshino, Kentaro Yamada, Suljid Jirintai, Putu Prathiwi Primadharsini, Shigeo Nagashima, Kazumoto Murata and Hiroaki Okamoto

Viruses 2024, 16(9), 1400; https://doi.org/10.3390/v16091400 (registering DOI) - 31 Aug 2024

Abstract

The zoonotic transmission of hepatitis E virus (HEV) genotypes 3 (HEV-3) and 4 (HEV-4), and rabbit HEV (HEV-3ra) has been documented. Vaccination against HEV infection depends on the capsid (open reading frame 2, ORF2) protein, which is highly immunogenic and elicits effective virus-neutralizing [...] Read more.

The zoonotic transmission of hepatitis E virus (HEV) genotypes 3 (HEV-3) and 4 (HEV-4), and rabbit HEV (HEV-3ra) has been documented. Vaccination against HEV infection depends on the capsid (open reading frame 2, ORF2) protein, which is highly immunogenic and elicits effective virus-neutralizing antibodies. Escherichia coli (E. coli) is utilized as an effective system for producing HEV-like particles (VLPs). However, research on the production of ORF2 proteins from these HEV genotypes in E. coli to form VLPs has been modest. In this study, we constructed 21 recombinant plasmids expressing various N-terminally and C-terminally truncated HEV ORF2 proteins for HEV-3, HEV-3ra, and HEV-4 in E. coli. We successfully obtained nine HEV-3, two HEV-3ra, and ten HEV-4 ORF2 proteins, which were primarily localized in inclusion bodies. These proteins were solubilized in 4 M urea, filtered, and subjected to gel filtration. Results revealed that six HEV-3, one HEV-3ra, and two HEV-4 truncated proteins could assemble into VLPs. The purified VLPs displayed molecular weights ranging from 27.1 to 63.4 kDa and demonstrated high purity (74.7–95.3%), as assessed by bioanalyzer, with yields of 13.9–89.6 mg per 100 mL of TB medium. Immunoelectron microscopy confirmed the origin of these VLPs from HEV ORF2. Antigenicity testing indicated that these VLPs possess characteristic HEV antigenicity. Evaluation of immunogenicity in Balb/cAJcl mice revealed robust anti-HEV IgG responses, highlighting the potential of these VLPs as immunogens. These findings suggest that the generated HEV VLPs of different genotypes could serve as valuable tools for HEV research and vaccine development. Full article

(This article belongs to the Special Issue Hepatitis E: Molecular Virology, Pathogenesis, and Treatment, 2nd Edition)

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18 pages, 2471 KiB

Open AccessArticle

The Prevalence and Molecular Characterization of Bovine Leukemia Virus among Dairy Cattle in Henan Province, China

by Yuxi Zhao, Xiaojie Zhu, Zhen Zhang, Jianguo Chen, Yingyu Chen, Changmin Hu, Xi Chen, Ian D. Robertson and Aizhen Guo

Viruses 2024, 16(9), 1399; https://doi.org/10.3390/v16091399 (registering DOI) - 31 Aug 2024

Abstract

Enzootic bovine leukosis, a neoplastic disease caused by the bovine leukemia virus (BLV), was the primary cancer affecting cattle in China before 1985. Although its prevalence decreased significantly between 1986 and 2000, enzootic bovine leukosis has been re-emerging since 2000. This re-emergence has [...] Read more.

Enzootic bovine leukosis, a neoplastic disease caused by the bovine leukemia virus (BLV), was the primary cancer affecting cattle in China before 1985. Although its prevalence decreased significantly between 1986 and 2000, enzootic bovine leukosis has been re-emerging since 2000. This re-emergence has been largely overlooked, possibly due to the latent nature of BLV infection or the perceived lack of sufficient evidence. This study investigated the molecular epidemiology of BLV infections in dairy cattle in Henan province, Central China. Blood samples from 668 dairy cattle across nine farms were tested using nested polymerase chain reaction assays targeting the partial envelope (env) gene (gp51 fragment). Twenty-three samples tested positive (animal-level prevalence of 3.4%; 95% confidence interval: 2.2, 5.1). The full-length env gene sequences from these positive samples were obtained and phylogenetically analyzed, along with previously reported sequences from the GenBank database. The sequences from positive samples were clustered into four genotypes (1, 4, 6, and 7). The geographical annotation of the maximum clade credibility trees suggested that the two genotype 1 strains in Henan might have originated from Japan, while the genotype 7 strain is likely to have originated from Moldova. Subsequent Bayesian stochastic search variable selection analysis further indicated a strong geographical association between the Henan strains and Japan, as well as Moldova. The estimated substitution rate for the env gene ranged from 4.39 × 10⁻⁴ to 2.38 × 10⁻³ substitutions per site per year. Additionally, codons 291, 326, 385, and 480 were identified as positively selected sites, potentially associated with membrane fusion, epitope peptide vaccine design, and transmembrane signal transduction. These findings contribute to the broader understanding of BLV epidemiology in Chinese dairy cattle and highlight the need for measures to mitigate further BLV transmission within and between cattle herds in China. Full article

(This article belongs to the Section Animal Viruses)

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12 pages, 779 KiB

Open AccessArticle

Wastewater Surveillance of SARS-CoV-2: A Comparison of Two Concentration Methods

by Christina Diamanti, Lambros Nousis, Petros Bozidis, Michalis Koureas, Maria Kyritsi, George Markozannes, Nikolaos Simantiris, Eirini Panteli, Anastasia Koutsolioutsou, Konstantinos Tsilidis, Christos Hadjichristodoulou, Alexandra Koutsotoli, Eirini Christaki, Dimitrios Alivertis, Aristides Bartzokas, Konstantina Gartzonika, Chrysostomos Dovas and Evangelia Ntzani

Viruses 2024, 16(9), 1398; https://doi.org/10.3390/v16091398 (registering DOI) - 31 Aug 2024

Abstract

Wastewater surveillance is crucial for the epidemiological monitoring of SARS-CoV-2. Various concentration techniques, such as skimmed milk flocculation (SMF) and polyethylene glycol (PEG) precipitation, are employed to isolate the virus effectively. This study aims to compare these two methods and determine the one [...] Read more.

Wastewater surveillance is crucial for the epidemiological monitoring of SARS-CoV-2. Various concentration techniques, such as skimmed milk flocculation (SMF) and polyethylene glycol (PEG) precipitation, are employed to isolate the virus effectively. This study aims to compare these two methods and determine the one with the superior recovery rates. From February to December 2021, 24-h wastewater samples were collected from the Ioannina Wastewater Treatment Plant’s inlet and processed using both techniques. Subsequent viral genome isolation and a real-time RT-qPCR detection of SARS-CoV-2 were performed. The quantitative analysis demonstrated a higher detection sensitivity with a PEG-based concentration than SMF. Moreover, when the samples were positive by both methods, PEG consistently yielded higher viral loads. These findings underscore the need for further research into concentration methodologies and the development of precise protocols to enhance epidemiological surveillance through wastewater analysis. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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21 pages, 1990 KiB

Open AccessArticle

Torque Teno Sus Virus 1: A Potential Surrogate Pathogen to Study Pig-Transmitted Transboundary Animal Diseases

by Xiaolong Li, Brandon M. Parker, Raoul K. Boughton, James C. Beasley, Timothy J. Smyser, James D. Austin, Kim M. Pepin, Ryan S. Miller, Kurt C. Vercauteren and Samantha M. Wisely

Viruses 2024, 16(9), 1397; https://doi.org/10.3390/v16091397 (registering DOI) - 31 Aug 2024

Abstract

Understanding the epidemiology and transmission dynamics of transboundary animal diseases (TADs) among wild pigs (Sus scrofa) will aid in preventing the introduction or containment of TADs among wild populations. Given the challenges associated with studying TADs in free-ranging populations, a surrogate [...] Read more.

Understanding the epidemiology and transmission dynamics of transboundary animal diseases (TADs) among wild pigs (Sus scrofa) will aid in preventing the introduction or containment of TADs among wild populations. Given the challenges associated with studying TADs in free-ranging populations, a surrogate pathogen system may predict how pathogens may circulate and be maintained within wild free-ranging swine populations, how they may spill over into domestic populations, and how management actions may impact transmission. We assessed the suitability of Torque teno sus virus 1 (TTSuV1) to serve as a surrogate pathogen for molecular epidemiological studies in wild pigs by investigating the prevalence, persistence, correlation with host health status and genetic variability at two study areas: Archbold’s Buck Island Ranch in Florida and Savannah River Site in South Carolina. We then conducted a molecular epidemiological case study within Archbold’s Buck Island Ranch site to determine how analysis of this pathogen could inform transmission dynamics of a directly transmitted virus. Prevalence was high in both study areas (40%, n = 190), and phylogenetic analyses revealed high levels of genetic variability within and between study areas. Our case study showed that pairwise host relatedness and geographic distance were highly correlated to pairwise viral genetic similarity. Molecular epidemiological analyses revealed a distinct pattern of direct transmission from pig to pig occurring within and between family groups. Our results suggest that TTSuV1 is highly suitable for molecular epidemiological analyses and will be useful for future studies of transmission dynamics in wild free-ranging pigs. Full article

(This article belongs to the Section Animal Viruses)

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12 pages, 4159 KiB

Open AccessArticle

Towards the Development of a Minigenome Assay for Species A Rotaviruses

by Ola Diebold, Shu Zhou, Colin Peter Sharp, Blanka Tesla, Hou Wei Chook, Paul Digard and Eleanor R. Gaunt

Viruses 2024, 16(9), 1396; https://doi.org/10.3390/v16091396 (registering DOI) - 31 Aug 2024

Abstract

RNA virus polymerases carry out multiple functions necessary for successful genome replication and transcription. A key tool for molecular studies of viral RNA-dependent RNA polymerases (RdRps) is a ‘minigenome’ or ‘minireplicon’ assay, in which viral RdRps are reconstituted in cells in the absence [...] Read more.

RNA virus polymerases carry out multiple functions necessary for successful genome replication and transcription. A key tool for molecular studies of viral RNA-dependent RNA polymerases (RdRps) is a ‘minigenome’ or ‘minireplicon’ assay, in which viral RdRps are reconstituted in cells in the absence of full virus infection. Typically, plasmids expressing the viral polymerase protein(s) and other co-factors are co-transfected, along with a plasmid expressing an RNA encoding a fluorescent or luminescent reporter gene flanked by viral untranslated regions containing cis-acting elements required for viral RdRp recognition. This reconstitutes the viral transcription/replication machinery and allows the viral RdRp activity to be measured as a correlate of the reporter protein signal. Here, we report on the development of a ‘first-generation’ plasmid-based minigenome assay for species A rotavirus using a firefly luciferase reporter gene. Full article

(This article belongs to the Special Issue Rotaviruses and Rotavirus Vaccines)

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12 pages, 1079 KiB

Open AccessArticle

Israeli Acute Paralysis Virus Is an Emerging Pathogen Contributing to Brood Disease of Apis cerana

by Yanling Xie, Shuai Wang, Yao Liu, Jie Deng, Xiaoling Su, Zhichu Huang and Huoqing Zheng

Viruses 2024, 16(9), 1395; https://doi.org/10.3390/v16091395 (registering DOI) - 31 Aug 2024

Abstract

Larval mortality is the primary symptom of diseased Apis cerana colonies, often attributed to sacbrood virus (SBV) and Melissococcus plutonius. However, the impact of other common honeybee viruses is frequently overlooked, and their pathogenicity to A. cerana remains poorly understood. To investigate the [...] Read more.

Larval mortality is the primary symptom of diseased Apis cerana colonies, often attributed to sacbrood virus (SBV) and Melissococcus plutonius. However, the impact of other common honeybee viruses is frequently overlooked, and their pathogenicity to A. cerana remains poorly understood. To investigate the causes of the increasing disease incidence in A. cerana brood, we conducted an epidemiological survey, collecting 70 samples from 19 sites across nine provinces in China. Furthermore, we examined the pathogenicity of Israeli acute paralysis virus (IAPV) in A. cerana brood through artificial inoculation experiments. Our results demonstrate that, besides SBV and M. plutonius, the infection rate and viral load of IAPV in diseased brood are significantly high. Brood artificially inoculated with high concentrations of IAPV exhibited a significant increase in mortality and displayed clinical symptoms similar to those observed in naturally infected colonies. Moreover, a limited resistance to IAPV was observed in A. cerana brood, with some individuals able to restrict viral proliferation. Our study highlights the previously unrecognized pathogenicity of IAPV to A. cerana brood, demonstrating that IAPV poses a significant threat similar to SBV and M. plutonius. We emphasize that IAPV should be recognized as an emerging pathogen causing brood disease in A. cerana and managed accordingly in beekeeping practices. Full article

(This article belongs to the Section Invertebrate Viruses)

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12 pages, 1704 KiB

Open AccessArticle

Circulation and Seasonality of Respiratory Viruses in Hospitalized Patients during Five Consecutive Years (2019–2023) in Perugia, Italy

by Alessandro Graziani, Silvia Bozza, Monica Borghi, Antonella Mencacci and Barbara Camilloni

Viruses 2024, 16(9), 1394; https://doi.org/10.3390/v16091394 (registering DOI) - 30 Aug 2024

Abstract

The emergence of SARS-CoV-2 and the non-pharmacological interventions adopted to counter its spread appear to have led to changes in the normal circulation and seasonality of respiratory viruses. Our study aims to investigate changes related to the circulation of respiratory viruses, not SARS-CoV-2, [...] Read more.

The emergence of SARS-CoV-2 and the non-pharmacological interventions adopted to counter its spread appear to have led to changes in the normal circulation and seasonality of respiratory viruses. Our study aims to investigate changes related to the circulation of respiratory viruses, not SARS-CoV-2, among hospitalized patients in Perugia, Central Italy, between 2019 and 2023. The samples were collected from individuals who went to the emergency room (ER) or were hospitalized and analyzed using a molecular multiplex test. The results underline that non-pharmaceutical interventions altered the typical seasonal circulation patterns of different respiratory viruses. Those mostly affected were enveloped viruses like influenza viruses that disappeared in 2021; the least impact was recorded for Rhinovirus, which was detected during the pandemic period, maintaining the same seasonality observed in the pre-pandemic period although with a reduction in the number of positive samples. Our data underline the importance of the continuous monitoring of these viruses, especially to understand the timing with which prevention measures, not only non-pharmacological interventions but also the equipment of vaccine doses and monoclonal antibodies, should be adopted to reduce their circulation, particularly in the population at risk of developing severe forms of lower respiratory tract infection. Full article

(This article belongs to the Special Issue The Influence of COVID-19 Pandemic on the Epidemiology of Other Human Viral Infections)

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15 pages, 627 KiB

Open AccessArticle

Patterns of Transmitted Drug Resistance Mutations and HIV-1 Subtype Dynamics in ART-Naïve Individuals in Veneto, Italy, from 2017 to 2024

by Nicholas Geremia, Monica Basso, Andrea De Vito, Renzo Scaggiante, Mario Giobbia, Giuliana Battagin, Federico Dal Bello, Maria Teresa Giordani, Stefano Nardi, Marina Malena, Annamaria Cattelan and Saverio Giuseppe Parisi

Viruses 2024, 16(9), 1393; https://doi.org/10.3390/v16091393 (registering DOI) - 30 Aug 2024

Abstract

This study investigates the prevalence and patterns of transmitted drug resistance mutations (TDRMs) and HIV-1 subtypes among antiretroviral therapy (ART) naïve individuals in Veneto, Italy, from 2017 to 2024. This research aims to understand the dynamic landscape of TDRMs and HIV-1 genetic diversity [...] Read more.

This study investigates the prevalence and patterns of transmitted drug resistance mutations (TDRMs) and HIV-1 subtypes among antiretroviral therapy (ART) naïve individuals in Veneto, Italy, from 2017 to 2024. This research aims to understand the dynamic landscape of TDRMs and HIV-1 genetic diversity to inform treatment strategies effectively. We included all adult ART-naïve people with HIV (PWH) from seven infectious disease units in Veneto, Italy. We collected the genotypic resistance testing conducted to predict drug susceptibility and subtype distribution using the Stanford HIVdb algorithm. We included 762 PWH, showing a slight but statistically significant decline in the B subtype among Italian PWH (p = 0.045) and an increase in non-B subtypes among foreigners, though it was not statistically significant (p = 0.333). The most frequent mutations were in Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), especially in non-B subtypes, with a notable rise from 10.7% in 2017–2019 to 15.5% in 2020–2024. Notably, TDRMs were consistently detected, highlighting an ongoing challenge despite the stable prevalence observed over the years. In addition, the data revealed a concerning rise in mutations against newer drug classes, such as integrase inhibitors. Conclusively, the study underscores the necessity of continuous surveillance of HIV subtypes and resistance patterns to adapt ART regimens optimally. Despite the stable levels of drug resistance, the emergence of resistance against newer drugs necessitates ongoing vigilance and possible adjustment in treatment protocols to enhance clinical outcomes and manage HIV drug resistance effectively. Full article

(This article belongs to the Special Issue Viral Resistance)

24 pages, 368 KiB

Open AccessReview

Treatment Management Challenges in Naïve and Experienced HIV-1-Infected Individuals Carrying the M184V Mutation

by Iordanis Mimtsoudis, Olga Tsachouridou, Karolina Akinosoglou and Symeon Metallidis

Viruses 2024, 16(9), 1392; https://doi.org/10.3390/v16091392 - 30 Aug 2024

Abstract

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation (RAM) is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in [...] Read more.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation (RAM) is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of the M184V mutation on the treatment outcomes in people living with HIV (PLWH). Since 3TC remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure (VF). ART guidelines do not recommend the use of drugs impacted by RAMs as they have been confirmed to comprise a risk factor for VF. However, there is evidence that 3TC/FTC can remain active even in the presence of M184V. Given the potential benefits of 3TC in ART combinations, the investigation of M184V remains of high interest to clinicians and researchers, especially in certain regions with limited resources, and especially for its unusual effects. This is a review of the literature on the challenges in treating both naïve and experienced individuals carrying the M184V mutation, including virological failure, virological suppression, and resistance to ART. Full article

(This article belongs to the Special Issue Current ART, Virologic Failure and Implications for HIV Drug Resistance)

22 pages, 3359 KiB

Open AccessArticle

Metabolic Dependency Shapes Bivalent Antiviral Response in Host Cells in Response to Poly:IC: The Role of Glutamine

by Grégorie Lebeau, Aurélie Paulo-Ramos, Mathilde Hoareau, Daed El Safadi, Olivier Meilhac, Pascale Krejbich-Trotot, Marjolaine Roche and Wildriss Viranaicken

Viruses 2024, 16(9), 1391; https://doi.org/10.3390/v16091391 - 30 Aug 2024

Abstract

The establishment of effective antiviral responses within host cells is intricately related to their metabolic status, shedding light on immunometabolism. In this study, we investigated the hypothesis that cellular reliance on glutamine metabolism contributes to the development of a potent antiviral response. We [...] Read more.

The establishment of effective antiviral responses within host cells is intricately related to their metabolic status, shedding light on immunometabolism. In this study, we investigated the hypothesis that cellular reliance on glutamine metabolism contributes to the development of a potent antiviral response. We evaluated the antiviral response in the presence or absence of L-glutamine in the culture medium, revealing a bivalent response hinging on cellular metabolism. While certain interferon-stimulated genes (ISGs) exhibited higher expression in an oxidative phosphorylation (OXPHOS)-dependent manner, others were surprisingly upregulated in a glycolytic-dependent manner. This metabolic dichotomy was influenced in part by variations in interferon-β (IFN-β) expression. We initially demonstrated that the presence of L-glutamine induced an enhancement of OXPHOS in A549 cells. Furthermore, in cells either stimulated by poly:IC or infected with dengue virus and Zika virus, a marked increase in ISGs expression was observed in a dose-dependent manner with L-glutamine supplementation. Interestingly, our findings unveiled a metabolic dependency in the expression of specific ISGs. In particular, genes such as ISG54, ISG12 and ISG15 exhibited heightened expression in cells cultured with L-glutamine, corresponding to higher OXPHOS rates and IFN-β signaling. Conversely, the expression of viperin and 2′-5′-oligoadenylate synthetase 1 was inversely related to L-glutamine concentration, suggesting a glycolysis-dependent regulation, confirmed by inhibition experiments. This study highlights the intricate interplay between cellular metabolism, especially glutaminergic and glycolytic, and the establishment of the canonical antiviral response characterized by the expression of antiviral effectors, potentially paving the way for novel strategies to modulate antiviral responses through metabolic interventions. Full article

(This article belongs to the Special Issue Host Cell-Virus Interaction, 3rd Edition)

13 pages, 1492 KiB

Open AccessArticle

Detection and Genetic Characterization of Border Disease Virus (BDV) Isolated from a Persistently Infected Sheep in a Migratory Flock from Rajasthan State, Northwestern India

by Semmannan Kalaiyarasu, Katherukamem Rajukumar, Niranjan Mishra, Shashi Bhusan Sudhakar and Vijendra Pal Singh

Viruses 2024, 16(9), 1390; https://doi.org/10.3390/v16091390 - 30 Aug 2024

Abstract

Border disease virus (BDV) causes significant economic losses in sheep farming worldwide. In India, BDV has not yet been studied in sheep migrating for summer pasturing. This study aimed to determine the extent of BDV infection in migratory sheep and provide genetic characteristics [...] Read more.

Border disease virus (BDV) causes significant economic losses in sheep farming worldwide. In India, BDV has not yet been studied in sheep migrating for summer pasturing. This study aimed to determine the extent of BDV infection in migratory sheep and provide genetic characteristics of BDV. Blood and serum samples from 90 lambs of a migratory sheep flock (600) in Central India were collected and subjected to molecular detection, phylogenetic analysis and virus neutralization test (VNT). We detected BDV in two lambs through real-time RT-PCR, while 64.4% (58/90) of in-contact lambs had BDV neutralizing antibodies. One apparently healthy lamb was found to be persistently infected with BDV. Phylogenetic analysis of 5′-UTR and N^pro genes and the concatenated datasets typed the BDV isolate from PI sheep as BDV-3 genotype. However, it showed a closer relationship with BDV-3 strains from China than the previously reported Indian BDV-3 strains. This is the first report on the detection of BDV persistently infected migratory sheep in India. Additionally, we provided evidence of genetic variability among BDV-3 strains in India. The findings improve our understanding of epidemiology and genetic characteristics of BDV in India and highlight the potential risks associated with the traditional practice of sheep migration for summer pasturing. Full article

(This article belongs to the Special Issue Pestivirus 2024)

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16 pages, 8230 KiB

Open AccessArticle

Molecular and Evolutionary Characteristics of Chicken Parvovirus (ChPV) Genomes Detected in Chickens with Runting–Stunting Syndrome

by Ruy D. Chacón, Christian J. Sánchez-Llatas, Antonio Charlys da Costa, Stefhany Valdeiglesias Ichillumpa, Pablo Cea-Callejo, Obert Marín-Sánchez, Claudete S. Astolfi-Ferreira, Silvana Santander-Parra, Luis F. N. Nuñez and Antonio J. Piantino Ferreira

Viruses 2024, 16(9), 1389; https://doi.org/10.3390/v16091389 - 30 Aug 2024

Abstract

Chicken Parvovirus (ChPV) belongs to the genus Aveparvovirus and is implicated in enteric diseases like runting–stunting syndrome (RSS) in poultry. In RSS, chicken health is affected by diarrhea, depression, and increased mortality, causing significant economic losses in the poultry industry. This study aimed [...] Read more.

Chicken Parvovirus (ChPV) belongs to the genus Aveparvovirus and is implicated in enteric diseases like runting–stunting syndrome (RSS) in poultry. In RSS, chicken health is affected by diarrhea, depression, and increased mortality, causing significant economic losses in the poultry industry. This study aimed to characterize the ChPV genomes detected in chickens with RSS through a metagenomic approach and compare the molecular and evolutionary characteristics within the Aveparvovirus galliform1 species. The intestinal content of broiler flocks affected with RSS was submitted to viral metagenomics. The assembled prevalent genomes were identified as ChPV after sequence and phylogenetic analysis, which consistently clustered separately from Turkey Parvovirus (TuPV). The strain USP-574-A presented signs of genomic recombination. The selective pressure analysis indicated that most of the coding genes in A. galliform1 are evolving under diversifying (negative) selection. Protein modeling of ChPV and TuPV viral capsids identified high conservancy over the VP2 region. The prediction of epitopes identified several co-localized antigenic peptides from ChPV and TuPV, especially for T-cell epitopes, highlighting the immunological significance of these sites. However, most of these peptides presented host-specific variability, obeying an adaptive scenario. The results of this study show the evolutionary path of ChPV and TuPV, which are influenced by diversifying events such as genomic recombination and selective pressure, as well as by adaptation processes, and their subsequent immunological impact. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2024)

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7 pages, 189 KiB

Open AccessCommentary

More than Just Buying a Van: Lessons Learned from a Mobile Telehealth HCV Testing and Treatment Study

by Elyse Bianchet, David de Gijsel, Lizbeth M. Del Toro-Mejias, Thomas J. Stopka, Randall A. Hoskinson, Jr., Patrick Dowd and Peter D. Friedmann

Viruses 2024, 16(9), 1388; https://doi.org/10.3390/v16091388 - 30 Aug 2024

Abstract

Hepatitis C virus (HCV) disproportionately affects people who inject drugs (PWID). Although HCV has become universally curable since the arrival of direct-acting antivirals, barriers exist to facilitating care and cure in this historically hard-to-reach population, including limited testing and healthcare services and healthcare [...] Read more.

Hepatitis C virus (HCV) disproportionately affects people who inject drugs (PWID). Although HCV has become universally curable since the arrival of direct-acting antivirals, barriers exist to facilitating care and cure in this historically hard-to-reach population, including limited testing and healthcare services and healthcare stigma, issues that are compounded in rural areas. Telehealth is effective in increasing access to HCV care and cure, but innovative approaches of testing and care are required to fully address the need among rural PWID, which led to our study examining a mobile telehealth model for treating HCV. In this commentary, we discuss lessons learned delivering telehealth on a mobile unit, important factors for consideration when designing a mobile intervention, and we suggest an ideal model to increase access to HCV testing and treatment and other services for rural PWID. Full article

(This article belongs to the Special Issue Hepatitis C Virus Infection among People Who Inject Drugs)

11 pages, 2218 KiB

Open AccessArticle

Acute Chikungunya Virus Infection Triggers a Diverse Range of T Helper Lymphocyte Profiles

by Ramayana Morais de Medeiros Brito, Marília Farias de Melo, José Veríssimo Fernandes, Joanna Gardel Valverde, Paulo Marcos Matta Guedes, Josélio Maria Galvão de Araújo and Manuela Sales Lima Nascimento

Viruses 2024, 16(9), 1387; https://doi.org/10.3390/v16091387 - 30 Aug 2024

Abstract

Chikungunya virus (CHIKV) is an arbovirus causing acute febrile illness with severe joint pain, often leading to chronic arthralgia. This study investigated the adaptive immune responses during the early stages of symptomatic acute CHIKV infection, focusing on the transcription factors and cytokines linked [...] Read more.

Chikungunya virus (CHIKV) is an arbovirus causing acute febrile illness with severe joint pain, often leading to chronic arthralgia. This study investigated the adaptive immune responses during the early stages of symptomatic acute CHIKV infection, focusing on the transcription factors and cytokines linked to Th1, Th2, Th17, and Treg cells. Thirty-six individuals were enrolled: nine healthy controls and 27 CHIKV-positive patients confirmed by qRT-PCR. Blood samples were analyzed for the mRNA expression of transcription factors (Tbet, GATA3, FoxP3, STAT3, RORγt) and cytokines (IFN-γ, IL-4, IL-17, IL-22, TGF-β, IL-10). The results showed the significant upregulation of Tbet, GATA3, FoxP3, STAT3, and RORγt in CHIKV-positive patients, with RORγt displaying the highest increase. Correspondingly, cytokines IFN-γ, IL-4, IL-17, and IL-22 were upregulated, while TGF-β was downregulated. Principal component analysis (PCA) confirmed the distinct immune profiles between CHIKV-positive and healthy individuals. A correlation analysis indicated that higher Tbet expression correlated with a lower viral load, whereas FoxP3 and TGF-β were associated with higher viral loads. Our study sheds light on the intricate immune responses during acute CHIKV infection, characterized by a mixed Th1, Th2, Th17, and Treg response profile. These results emphasize the complex interplay between different adaptive immune responses and how they may contribute to the pathogenesis of Chikungunya fever. Full article

(This article belongs to the Special Issue Innate and Adaptive Immune Responses to Arbovirus Infections)

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24 pages, 847 KiB

Open AccessReview

Like a Rolling Stone? A Review on Spontaneous Clearance of Hepatitis C Virus Infection

by Piotr Rzymski, Michał Brzdęk, Krystyna Dobrowolska, Barbara Poniedziałek, Aleksandra Murawska-Ochab, Dorota Zarębska-Michaluk and Robert Flisiak

Viruses 2024, 16(9), 1386; https://doi.org/10.3390/v16091386 - 30 Aug 2024

Abstract

Elimination of hepatitis C virus (HCV) without the need for medical intervention, known as spontaneous clearance (SC), occurs at a significantly lower rate than in the case of hepatitis B virus infection and only in selected individuals, such as reportedly in Keith Richards, [...] Read more.

Elimination of hepatitis C virus (HCV) without the need for medical intervention, known as spontaneous clearance (SC), occurs at a significantly lower rate than in the case of hepatitis B virus infection and only in selected individuals, such as reportedly in Keith Richards, a guitarist of The Rolling Stones. The present paper provides an updated narrative review of the research devoted to the phenomenon in order to identify and discuss the demographic, lifestyle-related, clinical, viral genotype-related, and host genetic factors underpinning the SC occurrence. The body of evidence indicates that the likelihood of SC is decreased in older individuals, men, Black people, HIV-coinfected subjects, and intravenous drug and alcohol users. In turn, HBV coinfection and specific polymorphism of the genes encoding interferon lambda 3 (particularly at rs8099917) and interferon lambda 4 (particularly at rs12979860) and HLA genes increase the odds of SC. Numerous other host-specific genetic factors could be implicated in SC, but the evidence is limited only to certain ethnic groups and often does not account for confounding variables. SC of HCV infection is a complex process arising from a combination of various factors, though a genetic component may play a leading role in some cases. Understanding factors influencing the likelihood of this phenomenon justifies better surveillance of high-risk groups, decreasing health inequities in particular ethnic groups, and may guide the development of a prophylactic vaccine, which at present is not available, or novel therapeutic strategies. Further research is needed to elucidate the exact mechanisms underlying SC and to explore potential interventions that could enhance this natural antiviral response. Full article

(This article belongs to the Special Issue Hepatitis C Virus 2024)

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14 pages, 1514 KiB

Open AccessArticle

Intra-Host Citrus Tristeza Virus Populations during Prolonged Infection Initiated by a Well-Defined Sequence Variant in Nicotiana benthamiana

by Tathiana Ferreira Sa Antunes, José C. Huguet-Tapia, Santiago F. Elena and Svetlana Y. Folimonova

Viruses 2024, 16(9), 1385; https://doi.org/10.3390/v16091385 - 30 Aug 2024

Abstract

Due to the error-prone nature of viral RNA-dependent RNA polymerases, the replication of RNA viruses results in a diversity of viral genomes harboring point mutations, deletions, insertions, and genome rearrangements. Citrus tristeza virus (CTV), a causal agent of diseases of economically important citrus [...] Read more.

Due to the error-prone nature of viral RNA-dependent RNA polymerases, the replication of RNA viruses results in a diversity of viral genomes harboring point mutations, deletions, insertions, and genome rearrangements. Citrus tristeza virus (CTV), a causal agent of diseases of economically important citrus species, shows intrinsic genetic stability. While the virus appears to have some mechanism that limits the accumulation of single-nucleotide variants, the production of defective viral genomes (DVGs) during virus infection has been reported for certain variants of CTV. The intra-host diversity generated during plant infection with variant T36 (CTV-T36) remains unclear. To address this, we analyzed the RNA species accumulated in the initially infected and systemic leaves of Nicotiana benthamiana plants inoculated with an infectious cDNA clone of CTV-T36, which warranted that infection was initiated by a known, well-defined sequence variant of the virus. CTV-T36 limited the accumulation of single-nucleotide mutants during infection. With that, four types of DVGs—deletions, insertions, and copy- and snap-backs—were found in all the samples, with deletions and insertions being the most common types. Hot-spots across the genome for DVG recombination and short direct sequence repeats suggest that sequence complementarity could mediate DVG formation. In conclusion, our study illustrates the formation of diverse DVGs during CTV-T36 infection. To the best of our knowledge, this is the first study that has analyzed the genetic variability and recombination of a well-defined sequence variant of CTV in an herbaceous host. Full article

(This article belongs to the Special Issue Viruses 2024 - A World of Viruses)

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11 pages, 978 KiB

Open AccessArticle

The Effect of a TLR3 Agonist on Airway Allergic Inflammation and Viral Infection in Immunoproteasome-Deficient Mice

by Niccolette Schaunaman, Taylor Nichols, Diana Cervantes, Paige Hartsoe, Deborah A. Ferrington and Hong Wei Chu

Viruses 2024, 16(9), 1384; https://doi.org/10.3390/v16091384 - 29 Aug 2024

Abstract

Allergic asthma is characterized by increased type 2 inflammation, including eosinophils. Subjects with allergic asthma have recurrent symptoms due to their constant exposure to environmental allergens, such as house dust mite (HDM), which can be further exacerbated by respiratory infections like rhinovirus. The [...] Read more.

Allergic asthma is characterized by increased type 2 inflammation, including eosinophils. Subjects with allergic asthma have recurrent symptoms due to their constant exposure to environmental allergens, such as house dust mite (HDM), which can be further exacerbated by respiratory infections like rhinovirus. The immunoproteasome (IP) is a proteolytic machinery that is induced by inflammatory mediators during virus infection, but the role of the IP in airway allergic inflammation during rhinovirus infection remains unknown. Wild-type (WT) and IP knockout (KO) mice were challenged with HDM. At 48 h after the last HDM challenge, mice were infected with rhinovirus 1B (RV-A1B) for 24 h. After HDM and RV-A1B treatment, IP KO (vs. WT) mice had significantly more lung eosinophils and neutrophils, as well as a significantly higher viral load, but less IFN-beta expression, compared to WT mice. A TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) treatment after RV-A1B infection in HDM-challenged IP KO mice significantly increased IFN-beta expression and reduced viral load, with a minimal effect on the number of inflammatory cells. Our data suggest that immunoproteasome is an important mechanism functioning to prevent excessive inflammation and viral infection in allergen-exposed mice, and that Poly I:C could be therapeutically effective in enhancing the antiviral response and lessening the viral burden in lungs with IP deficiency. Full article

(This article belongs to the Special Issue Rhinoviruses and Asthma)

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