Journal Description
Viruses
Viruses
is a peer-reviewed, open access journal of virology, published monthly online by MDPI. The American Society for Virology (ASV), Spanish Society for Virology (SEV), Canadian Society for Virology (CSV), Italian Society for Virology (SIV-ISV), Australasian Virology Society (AVS) and others are affiliated with Viruses and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, AGRIS, and other databases.
- Journal Rank: JCR - Q2 (Virology) / CiteScore - Q1 (Infectious Diseases)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 13.8 days after submission; acceptance to publication is undertaken in 2.5 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journals for Viruses include: COVID and Zoonotic Diseases.
Impact Factor:
4.7 (2022);
5-Year Impact Factor:
4.8 (2022)
Latest Articles
An Observational Study Suggests That Natural HAdV-36 Infection Decreases Blood Glucose Levels without Affecting Insulin Levels in Obese Young Subjects
Viruses 2024, 16(6), 922; https://doi.org/10.3390/v16060922 - 5 Jun 2024
Abstract
Human adenovirus-36 (HAdV-36) infection has been linked to obesity, low lipid levels, and improvements in blood glucose levels and insulin sensitivity in animal models and humans, although epidemiological studies remain controversial. Therefore, this study investigated the relationship between HAdV-36 seropositivity and glycemic control
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Human adenovirus-36 (HAdV-36) infection has been linked to obesity, low lipid levels, and improvements in blood glucose levels and insulin sensitivity in animal models and humans, although epidemiological studies remain controversial. Therefore, this study investigated the relationship between HAdV-36 seropositivity and glycemic control in youths. This observational study examined 460 youths (246 with normal weight and 214 obese subjects). All participants underwent assessments for anthropometry, blood pressure, circulating fasting levels of glucose, lipids, insulin, and anti-HAdV-36 antibodies; additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. In all, 57.17% of the subjects were HAdV-36 seropositive. Moreover, HAdV-36 seroprevalence was higher in obese subjects compared to their normal weight counterparts (59% vs. 55%). BMI (33.1 vs. 32.3 kg/m2, p = 0.03), and waist circumference (107 vs. 104 cm, p = 0.02), insulin levels (21 vs. 16.3 µU/mL, p = 0.003), and HOMA-IR (4.6 vs. 3.9, p = 0.02) were higher in HAdV-36-positive subjects with obesity compared to seronegative subjects. In the obese group, HAdV-36 seropositivity was associated with a reducing effect in blood glucose levels in a model adjusted for total cholesterol, triglyceride levels, age and sex (β = −10.44, p = 0.014). Furthermore, a statistically significant positive relationship was observed between HAdV-36 seropositivity and insulin levels in the obesity group. These findings suggest that natural HAdV-36 infection improves glycemic control but does not ameliorate hyperinsulinemia in obese subjects.
Full article
(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV), Volume II)
Open AccessArticle
Effect of Heat Shock Treatment on the Virulence of Grass Carp Reovirus in Rare Minnow Gobiocypris rarus
by
Qinwei Ni, Yanchang Fan, Simin Xiao and Liqun Lu
Viruses 2024, 16(6), 921; https://doi.org/10.3390/v16060921 - 5 Jun 2024
Abstract
The mode and outcome of fish–virus interactions are influenced by many abiotic factors, among which water temperature is especially important in poikilothermic fish. Rare minnow Gobiocypris rarus is a eurythermal small cyprinid fish that is sensitive to infection with genotype Ⅱ grass carp
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The mode and outcome of fish–virus interactions are influenced by many abiotic factors, among which water temperature is especially important in poikilothermic fish. Rare minnow Gobiocypris rarus is a eurythermal small cyprinid fish that is sensitive to infection with genotype Ⅱ grass carp reovirus (GCRV). HSP70, a conservative and key player in heat shock response, is previously identified as an induced pro-viral factor during GCRV infection in vitro. Here, rare minnow was subjected to heat shock treatment (HST), 1 h treatment at 32 °C followed by reverting to a normal temperature of 24 °C, and subsequently challenged with GCRV-II at a dosage of 1 × LD50. The effect of HST on GCRV virulence in vivo was evaluated by calculating virus-associated mortality and viral load in both dead and survival fish. The results revealed that HST enhanced the mortality of rare minnow infected with GCRV; the fact that viral loads in the tissue samples of HST-treated fish were significantly higher than those in samples of the control group at 6, 8 d p.i. reflected a faster infection process due to HST. Quantitative gene expression analysis was further employed to show that the expression levels of Hsp70 in intestine and liver tissues from the HST group declined faster than muscle tissue after HST. HST W/O GCRV challenge upregulated proinflammatory cytokines such as MyD88 and Nf-κB, which was in consistence with the inflammation observed in histopathological analysis. This study shed light on the complexity of the interaction between fish abiotic and biotic stress response, which suggested that HST, an abiotic stress, could enhance the virulence of GCRV in Gobiocypris rarus that involved modulating the gene expression of host heat shock, as well as a pro-inflammatory response.
Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction, 3rd Edition)
Open AccessArticle
Tepilamide Fumarate as a Novel Potentiator of Virus-Based Therapy
by
Akram Alwithenani, Rozanne Arulanandam, Boaz Wong, Marcus M. Spinelli, Andrew Chen, Glib Maznyi, Victoria H. Gilchrist, Tommy Alain and Jean-Simon Diallo
Viruses 2024, 16(6), 920; https://doi.org/10.3390/v16060920 - 5 Jun 2024
Abstract
Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges such as cellular resistance mediated by the interferon (IFN) response. Dimethyl fumarate (DMF) is used in the treatment of multiple sclerosis
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Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges such as cellular resistance mediated by the interferon (IFN) response. Dimethyl fumarate (DMF) is used in the treatment of multiple sclerosis and psoriasis and is recognized for its anti-cancer properties and has been shown to enhance both VSVΔ51 and HSV-1 oncolytic activity. Tepilamide fumarate (TPF) is a DMF analog currently undergoing clinical trials for the treatment of moderate-to-severe plaque psoriasis. The aim of this study was to evaluate the potential of TPF in enhancing the effectiveness of oncolytic viruses. In vitro, TPF treatment rendered 786-0 carcinoma cells more susceptible to VSVΔ51 infection, leading to increased viral replication. It outperformed DMF in both increasing viral infection and increasing the killing of these resistant cancer cells and other cancer cell lines tested. Ex vivo studies demonstrated TPF’s selective boosting of oncolytic virus infection in cancer cells without affecting healthy tissues. Effectiveness was notably high in pancreatic and ovarian tumor samples. Our study further indicates that TPF can downregulate the IFN pathway through a similar mechanism to DMF, making resistant cancer cells more vulnerable to viral infection. Furthermore, TPF’s impact on gene therapy was assessed, revealing its ability to enhance the transduction efficiency of vectors such as lentivirus, adenovirus type 5, and adeno-associated virus type 2 across various cell lines. This data underscore TPF’s potential role in not only oncolytic virotherapy but also in the broader application of gene therapy. Collectively, these findings position TPF as a promising agent in oncolytic virotherapy, warranting further exploration of its therapeutic potential.
Full article
(This article belongs to the Special Issue Progress and Prospects in Oncolytic Virotherapy)
Open AccessArticle
Discovery of Two Novel Viruses of the Willow-Carrot Aphid, Cavariella aegopodii
by
Gaoyang Jiao, Zhuangxin Ye, Kehui Feng, Chuanxi Zhang, Jianping Chen, Junmin Li and Yujuan He
Viruses 2024, 16(6), 919; https://doi.org/10.3390/v16060919 - 5 Jun 2024
Abstract
The advancement of bioinformatics and sequencing technology has resulted in the identification of an increasing number of new RNA viruses. This study systematically identified the RNA virome of the willow-carrot aphid, Cavariella aegopodii (Hemiptera: Aphididae), using metagenomic sequencing and rapid amplification of cDNA
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The advancement of bioinformatics and sequencing technology has resulted in the identification of an increasing number of new RNA viruses. This study systematically identified the RNA virome of the willow-carrot aphid, Cavariella aegopodii (Hemiptera: Aphididae), using metagenomic sequencing and rapid amplification of cDNA ends (RACE) approaches. C. aegopodii is a sap-sucking insect widely distributed in Europe, Asia, North America, and Australia. The deleterious effects of C. aegopodii on crop growth primarily stem from its feeding activities and its role as a vector for transmitting plant viruses. The virome includes Cavariella aegopodii virga-like virus 1 (CAVLV1) and Cavariella aegopodii iflavirus 1 (CAIV1). Furthermore, the complete genome sequence of CAVLV1 was obtained. Phylogenetically, CAVLV1 is associated with an unclassified branch of the Virgaviridae family and is susceptible to host antiviral RNA interference (RNAi), resulting in the accumulation of a significant number of 22nt virus-derived small interfering RNAs (vsiRNAs). CAIV1, on the other hand, belongs to the Iflaviridae family, with vsiRNAs ranging from 18 to 22 nt. Our findings present a comprehensive analysis of the RNA virome of C. aegopodii for the first time, offering insights that could potentially aid in the future control of the willow-carrot aphid.
Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
Open AccessArticle
Human Cytomegalovirus Dysregulates Cellular Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases and Sonic Hedgehog Pathway Proteins in Neural Astrocyte and Placental Models
by
Ece Egilmezer, Stuart T. Hamilton, Glen Lauw, Jasmine Follett, Eric Sonntag, Martin Schütz, Manfred Marschall and William D. Rawlinson
Viruses 2024, 16(6), 918; https://doi.org/10.3390/v16060918 - 5 Jun 2024
Abstract
Human cytomegalovirus (CMV) infection is the leading non-genetic cause of congenital malformation in developed countries, causing significant fetal injury, and in some cases fetal death. The pathogenetic mechanisms through which this host-specific virus infects then damages both the placenta and the fetal brain
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Human cytomegalovirus (CMV) infection is the leading non-genetic cause of congenital malformation in developed countries, causing significant fetal injury, and in some cases fetal death. The pathogenetic mechanisms through which this host-specific virus infects then damages both the placenta and the fetal brain are currently ill-defined. We investigated the CMV modulation of key signaling pathway proteins for these organs including dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) and Sonic Hedgehog (SHH) pathway proteins using human first trimester placental trophoblast (TEV-1) cells, primary human astrocyte (NHA) brain cells, and CMV-infected human placental tissue. Immunofluorescence demonstrated the accumulation and re-localization of SHH proteins in CMV-infected TEV-1 cells with Gli2, Ulk3, and Shh re-localizing to the CMV cytoplasmic virion assembly complex (VAC). In CMV-infected NHA cells, DYRK1A re-localized to the VAC and DYRK1B re-localized to the CMV nuclear replication compartments, and the SHH proteins re-localized with a similar pattern as was observed in TEV-1 cells. Western blot analysis in CMV-infected TEV-1 cells showed the upregulated expression of Rb, Ulk3, and Shh, but not Gli2. In CMV-infected NHA cells, there was an upregulation of DYRK1A, DYRK1B, Gli2, Rb, Ulk3, and Shh. These in vitro monoculture findings are consistent with patterns of protein upregulation and re-localization observed in naturally infected placental tissue and CMV-infected ex vivo placental explant histocultures. This study reveals CMV-induced changes in proteins critical for fetal development, and identifies new potential targets for CMV therapeutic development.
Full article
(This article belongs to the Special Issue Molecular Biology of Human Cytomegalovirus)
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Open AccessArticle
Recombinant Viruses from the Picornaviridae Family Occurring in Racing Pigeons
by
Ewa Łukaszuk, Daria Dziewulska and Tomasz Stenzel
Viruses 2024, 16(6), 917; https://doi.org/10.3390/v16060917 - 4 Jun 2024
Abstract
Viruses from Picornaviridae family are known pathogens of poultry, although the information on their occurrence and pathogenicity in pigeons is scarce. In this research, efforts are made to broaden the knowledge on Megrivirus B and Pigeon picornavirus B prevalence, phylogenetic relationship with other
[...] Read more.
Viruses from Picornaviridae family are known pathogens of poultry, although the information on their occurrence and pathogenicity in pigeons is scarce. In this research, efforts are made to broaden the knowledge on Megrivirus B and Pigeon picornavirus B prevalence, phylogenetic relationship with other avian picornaviruses and their possible connection with enteric disease in racing pigeons. As a result of Oxford Nanopore Sequencing, five Megrivirus and two pigeon picornavirus B-like genome sequences were recovered, among which three recombinant strains were detected. The recombinant fragments represented an average of 10.9% and 25.5% of the genome length of the Pigeon picornavirus B and Megrivirus B reference strains, respectively. The phylogenetic analysis revealed that pigeons are carriers of species-specific picornaviruses. TaqMan qPCR assays revealed 7.8% and 19.0% prevalence of Megrivirus B and 32.2% and 39.7% prevalence of Pigeon picornavirus B in the group of pigeons exhibiting signs of enteropathy and in the group of asymptomatic pigeons, respectively. In turn, digital droplet PCR showed a considerably higher number of genome copies of both viruses in sick than in asymptomatic pigeons. The results of quantitative analysis leave the role of picornaviruses in enteropathies of pigeons unclear.
Full article
(This article belongs to the Special Issue Enteric and Respiratory Viruses in Animals and Birds: Volume 5)
Open AccessArticle
Intrinsic Disorder in the Host Proteins Entrapped in Rabies Virus Particles
by
Hafiza Nimra Ashraf and Vladimir N. Uversky
Viruses 2024, 16(6), 916; https://doi.org/10.3390/v16060916 - 4 Jun 2024
Abstract
A proteomics analysis of purified rabies virus (RABV) revealed 47 entrapped host proteins within the viral particles. Out of these, 11 proteins were highly disordered. Our study was particularly focused on five of the RABV-entrapped mouse proteins with the highest levels of disorder:
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A proteomics analysis of purified rabies virus (RABV) revealed 47 entrapped host proteins within the viral particles. Out of these, 11 proteins were highly disordered. Our study was particularly focused on five of the RABV-entrapped mouse proteins with the highest levels of disorder: Neuromodulin, Chmp4b, DnaJB6, Vps37B, and Wasl. We extensively utilized bioinformatics tools, such as FuzDrop, D2P2, UniProt, RIDAO, STRING, AlphaFold, and ELM, for a comprehensive analysis of the intrinsic disorder propensity of these proteins. Our analysis suggested that these disordered host proteins might play a significant role in facilitating the rabies virus pathogenicity, immune system evasion, and the development of antiviral drug resistance. Our study highlighted the complex interaction of the virus with its host, with a focus on how the intrinsic disorder can play a crucial role in virus pathogenic processes, and suggested that these intrinsically disordered proteins (IDPs) and disorder-related host interactions can also be a potential target for therapeutic strategies.
Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction, 3rd Edition)
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Open AccessArticle
Reference Material Production and Milk Protein Concentration as Elements to Improve Bluetongue Serological Diagnosis in Bulk Tank Milk
by
David Romero-Trancón, Marta Valero-Lorenzo, Montserrat Agüero and Rubén Villalba
Viruses 2024, 16(6), 915; https://doi.org/10.3390/v16060915 - 4 Jun 2024
Abstract
The serological surveillance of bluetongue in bulk tank milk is an efficient and cost-effective method for the early detection of bluetongue virus incursions in unvaccinated free areas of the disease. In addition, the availability of standardized and reliable reagents and refined diagnostic procedures
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The serological surveillance of bluetongue in bulk tank milk is an efficient and cost-effective method for the early detection of bluetongue virus incursions in unvaccinated free areas of the disease. In addition, the availability of standardized and reliable reagents and refined diagnostic procedures with high sensitivity and specificity are essential for surveillance purposes. However, no available reference materials for bluetongue virus serological surveillance in bulk tank milk exist. This study shows the production and characterization of reference material for the implementation of a commercially available bluetongue milk ELISA test in official laboratories, as well as the evaluation of a procedure to increase the sensitivity in samples with low levels of antibodies. This procedure, based on milk protein concentration, allowed us to notably increase the ELISA test’s analytical sensitivity, which is useful for milk samples from farms with low within-herd prevalence or pools of bulk tank milk samples. The standardized milk reference material produced here, together with the evaluated procedure to improve analytical sensitivity, could be applied as tools to ensure an accurate diagnosis by official laboratories in bluetongue unvaccinated free areas.
Full article
(This article belongs to the Special Issue Bluetongue, Epizootic Haemorrhagic Disease, and Other Emerging Orbiviruses)
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Open AccessArticle
ISKNV Triggers AMPK/mTOR-Mediated Autophagy Signaling through Oxidative Stress, Inducing Antioxidant Enzyme Expression and Enhancing Viral Replication in GF-1 Cells
by
Tsai-Ching Hsueh, Pin-Han Chen and Jiann-Ruey Hong
Viruses 2024, 16(6), 914; https://doi.org/10.3390/v16060914 - 4 Jun 2024
Abstract
Infectious spleen and kidney necrosis virus (ISKNV) infections can induce the process of host cellular autophagy but have rarely been identified within the molecular autophagy signaling pathway. In the present study, we demonstrated that ISKNV induces ROS-mediated oxidative stress signals for the induction
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Infectious spleen and kidney necrosis virus (ISKNV) infections can induce the process of host cellular autophagy but have rarely been identified within the molecular autophagy signaling pathway. In the present study, we demonstrated that ISKNV induces ROS-mediated oxidative stress signals for the induction of 5′AMP-activated protein kinase/mechanistic target of rapamycin kinase (AMPK/mTOR)-mediated autophagy and upregulation of host antioxidant enzymes in fish GF-1 cells. We also examined ISKNV-induced oxidative stress, finding that reactive oxidative species (ROS) increased by 1.5-fold and 2.5-fold from day 2 to day 3, respectively, as assessed by the H2DCFDA assay for tracing hydrogen peroxide (H2O2), which was blocked by NAC treatment in fish GF-1 cells. Furthermore, ISKNV infection was shown to trigger oxidative stress/Nrf2 signaling from day 1 to day 3; this event was then correlated with the upregulation of antioxidant enzymes such as Cu/ZnSOD and MnSOD and was blocked by the antioxidant NAC. Using an MDC assay, TEM analysis and autophagy marker LC3-II/I ratio, we found that ROS stress can regulate autophagosome formation within the induction of autophagy, which was inhibited by NAC treatment in GF-1 cells. Through signal analysis, we found that AMPK/mTOR flux was modulated through inhibition of mTOR and activation of AMPK, indicating phosphorylation levels of mTOR Ser 2448 and AMPK Thr 172 from day 1 to day 3; however, this process was reversed by NAC treatment, which also caused a reduction in virus titer (TCID50%) of up to 1000 times by day 3 in GF-1 cells. Thus, ISKNV-induced oxidative stress signaling is blocked by antioxidant NAC, which can also either suppress mTOR/AMPK autophagic signals or reduce viral replication. These findings may provide the basis for the creation of DNA control and treatment strategies.
Full article
(This article belongs to the Special Issue Iridoviruses, 2nd Edition)
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Open AccessReview
Genetic Variations of African Swine Fever Virus: Major Challenges and Prospects
by
Shengmei Chen, Tao Wang, Rui Luo, Zhanhao Lu, Jing Lan, Yuan Sun, Qiang Fu and Hua-Ji Qiu
Viruses 2024, 16(6), 913; https://doi.org/10.3390/v16060913 - 4 Jun 2024
Abstract
African swine fever (ASF) is a contagious viral disease affecting pigs and wild boars. It typically presents as a hemorrhagic fever but can also manifest in various forms, ranging from acute to asymptomatic. ASF has spread extensively globally, significantly impacting the swine industry.
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African swine fever (ASF) is a contagious viral disease affecting pigs and wild boars. It typically presents as a hemorrhagic fever but can also manifest in various forms, ranging from acute to asymptomatic. ASF has spread extensively globally, significantly impacting the swine industry. The complex and highly variable character of the ASFV genome makes vaccine development and disease surveillance extremely difficult. The overall trend in ASFV evolution is towards decreased virulence and increased transmissibility. Factors such as gene mutation, viral recombination, and the strain-specificity of virulence-associated genes facilitate viral variations. This review deeply discusses the influence of these factors on viral immune evasion, pathogenicity, and the ensuing complexities encountered in vaccine development, disease detection, and surveillance. The ultimate goal of this review is to thoroughly explore the genetic evolution patterns and variation mechanisms of ASFV, providing a theoretical foundation for advancement in vaccine and diagnostic technologies.
Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Mutations in the Receptor Binding Domain of Severe Acute Respiratory Coronavirus-2 Omicron Variant Spike Protein Significantly Stabilizes Its Conformation
by
Michael H. Peters
Viruses 2024, 16(6), 912; https://doi.org/10.3390/v16060912 - 4 Jun 2024
Abstract
The Omicron variant and its sub-lineages are the only current circulating SARS-CoV-2 viruses worldwide. In this study, the conformational stability of the isolated Receptor Binding Domain (RBD) of Omicron’s spike protein is examined in detail. The parent Omicron lineage has over ten mutations
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The Omicron variant and its sub-lineages are the only current circulating SARS-CoV-2 viruses worldwide. In this study, the conformational stability of the isolated Receptor Binding Domain (RBD) of Omicron’s spike protein is examined in detail. The parent Omicron lineage has over ten mutations in the ACE2 binding region of the RBD that are specifically associated with its β hairpin loop domain. It is demonstrated through biophysical molecular computations that the mutations in the β hairpin loop domain significantly increase the intra-protein interaction energies of intra-loop and loop–RBD interactions. The interaction energy increases include the formation of new hydrogen bonds in the β hairpin loop domain that help stabilize this critical ACE2 binding region. Our results also agree with recent experiments on the stability of Omicron’s core β barrel domain, outside of its loop domain, and help demonstrate the overall conformational stability of the Omicron RBD. It is further shown here through dynamic simulations that the unbound state of the Omicron RBD remains closely aligned with the bound state configuration, which was not observed for the wild-type RBD. Overall, these studies demonstrate the significantly increased conformational stability of Omicron over its wild-type configuration and raise a number of questions on whether conformational stability could be a positive selection feature of SARS-CoV-2 viral mutational changes.
Full article
(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)
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Open AccessReview
The Use of Broadly Neutralizing Antibodies (bNAbs) in HIV-1 Treatment and Prevention
by
Jannifer Jasmin Thavarajah, Bo Langhoff Hønge and Christian Morberg Wejse
Viruses 2024, 16(6), 911; https://doi.org/10.3390/v16060911 - 4 Jun 2024
Abstract
Background: Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the
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Background: Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the imperative need for alternative therapeutic and preventative approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative, and possibly curative interventions against HIV infection. Objective: This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1-infected individuals. Main findings: Recent findings from clinical trials have highlighted the potential of bNAbs in the treatment, prevention, and quest for an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effectively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization with bNAb has provided a “proof of concept” for antibody-mediated prevention against HIV-1 acquisition, although complete prevention has not been obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative.
Full article
(This article belongs to the Special Issue Retroviral Recombination and Genetic Diversity)
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Open AccessArticle
Respiratory Virus-Induced PARP1 Alters DC Metabolism and Antiviral Immunity Inducing Pulmonary Immunopathology
by
Mohamed M. Mire, Srikanth Elesela, Susan Morris, Gabriel Corfas, Andrew Rasky and Nicholas W. Lukacs
Viruses 2024, 16(6), 910; https://doi.org/10.3390/v16060910 - 4 Jun 2024
Abstract
Previous studies from our laboratory and others have established the dendritic cell (DC) as a key target of RSV that drives infection-induced pathology. Analysis of RSV-induced transcriptomic changes in RSV-infected DC revealed metabolic gene signatures suggestive of altered cellular metabolism. Reverse phase protein
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Previous studies from our laboratory and others have established the dendritic cell (DC) as a key target of RSV that drives infection-induced pathology. Analysis of RSV-induced transcriptomic changes in RSV-infected DC revealed metabolic gene signatures suggestive of altered cellular metabolism. Reverse phase protein array (RPPA) data showed significantly increased PARP1 phosphorylation in RSV-infected DC. Real-time cell metabolic analysis demonstrated increased glycolysis in PARP1-/- DC after RSV infection, confirming a role for PARP1 in regulating DC metabolism. Our data show that enzymatic inhibition or genomic ablation of PARP1 resulted in increased ifnb1, il12, and il27 in RSV-infected DC which, together, promote a more appropriate anti-viral environment. PARP1-/- mice and PARP1-inhibitor-treated mice were protected against RSV-induced immunopathology including airway inflammation, Th2 cytokine production, and mucus hypersecretion. However, delayed treatment with PARP1 inhibitor in RSV-infected mice provided only partial protection, suggesting that PARP1 is most important during the earlier innate immune stage of RSV infection.
Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Open AccessArticle
Coxsackievirus A7 and Enterovirus A71 Significantly Reduce SARS-CoV-2 Infection in Cell and Animal Models
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Victor A. Svyatchenko, Stanislav S. Legostaev, Roman Y. Lutkovskiy, Elena V. Protopopova, Eugenia P. Ponomareva, Vladimir V. Omigov, Oleg S. Taranov, Vladimir A. Ternovoi, Alexander P. Agafonov and Valery B. Loktev
Viruses 2024, 16(6), 909; https://doi.org/10.3390/v16060909 - 4 Jun 2024
Abstract
In this study, we investigated the features of co-infection with SARS-CoV-2 and the enterovirus vaccine strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-CoV-2 and LEV-8 or EV-A71 in the cell
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In this study, we investigated the features of co-infection with SARS-CoV-2 and the enterovirus vaccine strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-CoV-2 and LEV-8 or EV-A71 in the cell model showed that a competitive inhibitory effect for these viruses was especially significant against SARS-CoV-2. Pre-infection with enteroviruses in the animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tract and more rapid clearance of infectious SARS-CoV-2 from the lower respiratory tract. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection in the animals. Additionally, the histological data illustrated that co-infection with strain LEV8 of coxsackievirus A7 decreased the level of pathological changes induced by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of the antiviral immune response, which is associated with the significant inhibition of SARS-CoV-2 infection. These results demonstrate that there is significant viral interference between the studied strain LEV-8 of coxsackievirus A7 or enterovirus A71 and SARS-CoV-2 in vitro and in vivo.
Full article
(This article belongs to the Special Issue Impact of Co-infections in COVID-19: Predisposing Mechanisms and Interplay between Invasive Viral, Bacterial and Fungal Pathogens)
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Open AccessReview
Significance of Cellular Lipid Metabolism for the Replication of Rotaviruses and Other RNA Viruses
by
Ulrich Desselberger
Viruses 2024, 16(6), 908; https://doi.org/10.3390/v16060908 - 4 Jun 2024
Abstract
The replication of species A rotaviruses (RVAs) involves the recruitment of and interaction with cellular organelles’ lipid droplets (LDs), both physically and functionally. The inhibition of enzymes involved in the cellular fatty acid biosynthesis pathway or the inhibition of cellular lipases that degrade
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The replication of species A rotaviruses (RVAs) involves the recruitment of and interaction with cellular organelles’ lipid droplets (LDs), both physically and functionally. The inhibition of enzymes involved in the cellular fatty acid biosynthesis pathway or the inhibition of cellular lipases that degrade LDs was found to reduce the functions of ‘viral factories’ (viroplasms for rotaviruses or replication compartments of other RNA viruses) and decrease the production of infectious progeny viruses. While many other RNA viruses utilize cellular lipids for their replication, their detailed analysis is far beyond this review; only a few annotations are made relating to hepatitis C virus (HCV), enteroviruses, SARS-CoV-2, and HIV-1.
Full article
(This article belongs to the Special Issue Viruses 2024 - A World of Viruses)
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Open AccessArticle
Evolutionary and Phylogenetic Dynamics of SARS-CoV-2 Variants: A Genetic Comparative Study of Taiyuan and Wuhan Cities of China
by
Behzad Hussain and Wu Changxin
Viruses 2024, 16(6), 907; https://doi.org/10.3390/v16060907 - 3 Jun 2024
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense, single-stranded RNA genome-containing virus which has infected millions of people all over the world. The virus has been mutating rapidly enough, resulting in the emergence of new variants and sub-variants which have reportedly
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense, single-stranded RNA genome-containing virus which has infected millions of people all over the world. The virus has been mutating rapidly enough, resulting in the emergence of new variants and sub-variants which have reportedly been spread from Wuhan city in China, the epicenter of the virus, to the rest of China and all over the world. The occurrence of mutations in the viral genome, especially in the viral spike protein region, has resulted in the evolution of multiple variants and sub-variants which gives the virus the benefit of host immune evasion and thus renders modern-day vaccines and therapeutics ineffective. Therefore, there is a continuous need to study the genetic characteristics and evolutionary dynamics of the SARS-CoV-2 variants. Hence, in this study, a total of 832 complete genomes of SARS-CoV-2 variants from the cities of Taiyuan and Wuhan in China was genetically characterized and their phylogenetic and evolutionary dynamics studied using phylogenetics, genetic similarity, and phylogenetic network analyses. This study shows that the four most prevalent lineages in Taiyuan and Wuhan are as follows: the Omicron lineages EG.5.1.1, followed by HK.3, FY.3, and XBB.1.16 (Pangolin classification), and clades 23F (EG.5.1), followed by 23H (HK.3), 22F (XBB), and 23D (XBB.1.9) (Nextclade classification), and lineage B followed by the Omicron FY.3, lineage A, and Omicron FL.2.3 (Pangolin classification), and the clades 19A, followed by 22F (XBB), 23F (EG.5.1), and 23H (HK.3) (Nextclade classification), respectively. Furthermore, our genetic similarity analysis show that the SARS-CoV-2 clade 19A-B.4 from Wuhan (name starting with 412981) has the least genetic similarity of about 95.5% in the spike region of the genome as compared to the query sequence of Omicron XBB.2.3.2 from Taiyuan (name starting with 18495234), followed by the Omicron FR.1.4 from Taiyuan (name starting with 18495199) with ~97.2% similarity and Omicron DY.3 (name starting with 17485740) with ~97.9% similarity. The rest of the variants showed ≥98% similarity with the query sequence of Omicron XBB.2.3.2 from Taiyuan (name starting with 18495234). In addition, our recombination analysis results show that the SARS-CoV-2 variants have three statistically significant recombinant events which could have possibly resulted in the emergence of Omicron XBB.1.16 (recombination event 3), FY.3 (recombination event 5), and FL.2.4 (recombination event 7), suggesting some very important information regarding viral evolution. Also, our phylogenetic tree and network analyses show that there are a total of 14 clusters and more than 10,000 mutations which may have probably resulted in the emergence of cluster-I, followed by 47 mutations resulting in the emergence of cluster-II and so on. The clustering of the viral variants of both cities reveals significant information regarding the phylodynamics of the virus among them. The results of our temporal phylogenetic analysis suggest that the variants of Taiyuan have likely emerged as independent variants separate from the variants of Wuhan. This study, to the best of our knowledge, is the first ever genetic comparative study between Taiyuan and Wuhan cities in China. This study will help us better understand the virus and cope with the emergence and spread of new variants at a local as well as an international level, and keep the public health authorities informed for them to make better decisions in designing new viral vaccines and therapeutics. It will also help the outbreak investigators to better examine any future outbreak.
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(This article belongs to the Section Coronaviruses)
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Exploring Dengue Dynamics: A Multi-Scale Analysis of Spatio-Temporal Trends in Ibagué, Colombia
by
Julian Otero, Alejandra Tabares and Mauricio Santos-Vega
Viruses 2024, 16(6), 906; https://doi.org/10.3390/v16060906 - 3 Jun 2024
Abstract
Our study examines how dengue fever incidence is associated with spatial (demographic and socioeconomic) alongside temporal (environmental) factors at multiple scales in the city of Ibagué, located in the Andean region of Colombia. We used the dengue incidence in Ibagué from 2013 to
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Our study examines how dengue fever incidence is associated with spatial (demographic and socioeconomic) alongside temporal (environmental) factors at multiple scales in the city of Ibagué, located in the Andean region of Colombia. We used the dengue incidence in Ibagué from 2013 to 2018 to examine the associations with climate, socioeconomic, and demographic factors from the national census and satellite imagery at four levels of local spatial aggregation. We used geographically weighted regression (GWR) to identify the relevant socioeconomic and demographic predictors, and we then integrated them with environmental variables into hierarchical models using integrated nested Laplace approximation (INLA) to analyze the spatio-temporal interactions. Our findings show a significant effect of spatial variables across the different levels of aggregation, including human population density, gas and sewage connection, percentage of woman and children, and percentage of population with a higher education degree. Lagged temporal variables displayed consistent patterns across all levels of spatial aggregation, with higher temperatures and lower precipitation at short lags showing an increase in the relative risk (RR). A comparative evaluation of the models at different levels of aggregation revealed that, while higher aggregation levels often yield a better overall model fit, finer levels offer more detailed insights into the localized impacts of socioeconomic and demographic variables on dengue incidence. Our results underscore the importance of considering macro and micro-level factors in epidemiological modeling, and they highlight the potential for targeted public health interventions based on localized risk factor analyses. Notably, the intermediate levels emerged as the most informative, thereby balancing spatial heterogeneity and case distribution density, as well as providing a robust framework for understanding the spatial determinants of dengue.
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(This article belongs to the Special Issue Arboviruses and Climate)
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Open AccessArticle
Lung Ultrasonography in the Evaluation of Late Sequelae of COVID-19 Pneumonia—A Comparison with Chest Computed Tomography: A Prospective Study
by
Katarzyna Zimna, Małgorzata Sobiecka, Jacek Wakuliński, Dorota Wyrostkiewicz, Ewa Jankowska, Monika Szturmowicz and Witold Z. Tomkowski
Viruses 2024, 16(6), 905; https://doi.org/10.3390/v16060905 - 3 Jun 2024
Abstract
The onset of the COVID-19 pandemic allowed physicians to gain experience in lung ultrasound (LUS) during the acute phase of the disease. However, limited data are available on LUS findings during the recovery phase. The aim of this study was to evaluate the
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The onset of the COVID-19 pandemic allowed physicians to gain experience in lung ultrasound (LUS) during the acute phase of the disease. However, limited data are available on LUS findings during the recovery phase. The aim of this study was to evaluate the utility of LUS to assess lung involvement in patients with post-COVID-19 syndrome. This study prospectively enrolled 72 patients who underwent paired LUS and chest CT scans (112 pairs including follow-up). The most frequent CT findings were ground glass opacities (83.3%), subpleural lines (72.2%), traction bronchiectasis (37.5%), and consolidations (31.9%). LUS revealed irregular pleural lines as a common abnormality initially (56.9%), along with subpleural consolidation >2.5 mm ≤10 mm (26.5%) and B-lines (26.5%). A strong correlation was found between LUS score, calculated by artificial intelligence percentage involvement in ground glass opacities described in CT (r = 0.702, p < 0.05). LUS score was significantly higher in the group with fibrotic changes compared to the non-fibrotic group with a mean value of 19.4 ± 5.7 to 11 ± 6.6, respectively (p < 0.0001). LUS might be considered valuable for examining patients with persistent symptoms after recovering from COVID-19 pneumonia. Abnormalities identified through LUS align with CT scan findings; thus, LUS might potentially reduce the need for frequent chest CT examinations.
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(This article belongs to the Special Issue COVID-19 and Pneumonia 3rd Edition)
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Open AccessReview
HPV16 Phylogenetic Variants in Anogenital and Head and Neck Cancers: State of the Art and Perspectives
by
Luisa Galati, Paola Di Bonito, Mariarosaria Marinaro, Maria Vincenza Chiantore and Tarik Gheit
Viruses 2024, 16(6), 904; https://doi.org/10.3390/v16060904 - 3 Jun 2024
Abstract
HPV16 is responsible for approximately 60% and 90% of global HPV–induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A–D). Our understanding of HPV16 variants mostly derives from epidemiological studies
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HPV16 is responsible for approximately 60% and 90% of global HPV–induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A–D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named “non-European” variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named “European variants”) has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV–related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV–driven anogenital and head and neck cancers.
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(This article belongs to the Section Human Virology and Viral Diseases)
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HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy
by
Uma Maheswari Deshetty, Nivedita Chatterjee, Shilpa Buch and Palsamy Periyasamy
Viruses 2024, 16(6), 903; https://doi.org/10.3390/v16060903 - 3 Jun 2024
Abstract
Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced the occurrence of comorbidities, including ocular manifestations. The involvement of endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation with cellular senescence or its role in initiating
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Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced the occurrence of comorbidities, including ocular manifestations. The involvement of endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation with cellular senescence or its role in initiating senescent traits. This study investigated how ER stress and dysregulated autophagy impact cellular senescence triggered by HIV-1 Tat in the MIO-M1 cell line (human Müller glial cells). Cells exposed to HIV-1 Tat exhibited increased vimentin expression combined with markers of ER stress (BiP, p-eIF2α), autophagy (LC3, Beclin-1, p62), and the senescence marker p21 compared to control cells. Western blotting and staining techniques like SA-β-gal were employed to examine these markers. Additionally, treatments with ER stress inhibitor 4-PBA before HIV-1 Tat exposure led to a decreased expression of ER stress, senescence, and autophagy markers. Conversely, pre-treatment with the autophagy inhibitor 3-MA resulted in reduced autophagy and senescence markers but did not alter ER stress markers compared to control cells. The findings suggest a link between ER stress, dysregulated autophagy, and the initiation of a senescence phenotype in MIO-M1 cells induced by HIV-1 Tat exposure.
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(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)
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