Viruses

16 pages, 2895 KiB

Open AccessArticle

Epidemiological and Molecular Investigation of Feline Panleukopenia Virus Infection in China

by Yinghui Wen, Zhengxu Tang, Kunli Wang, Zhengyang Geng, Simin Yang, Junqing Guo, Yongzhen Chen, Jiankun Wang, Zhiyu Fan, Pengju Chen and Jing Qian

Viruses 2024, 16(12), 1967; https://doi.org/10.3390/v16121967 - 23 Dec 2024

Viewed by 575

Abstract

The feline panleukopenia virus (FPV) is a highly contagious virus that affects cats worldwide, characterized by leukopenia, high temperature and diarrhea. Recently, the continuous prevalence and variation of FPV have attracted widespread concern. The aim of this study was to investigate the isolation, [...] Read more.

The feline panleukopenia virus (FPV) is a highly contagious virus that affects cats worldwide, characterized by leukopenia, high temperature and diarrhea. Recently, the continuous prevalence and variation of FPV have attracted widespread concern. The aim of this study was to investigate the isolation, genetic evolution, molecular characterization and epidemiological analysis of FPV strains among cats and dogs in China from 2019 to 2024. The 41 FPV strains, including 38 feline strains and 3 canine strains, were isolated from rectal swab samples by inoculating monolayer FK81 cells and performing a plaque purification assay. The viral and hemagglutination titers of these 41 FPV strains were 10^4.33~10^6.33 TCID₅₀/0.1 mL and 7.0 log₂~9.7 log₂, respectively. Based on the complete VP2 gene, the nucleotide homology of these FPV strains was 98.91~100%, and the homology with 24 reference FPV strains from different countries and hosts was 98.85~100%. The phylogenetic analysis revealed that 41 FPV strains were more closely related to the FPV strains of Asian origin (Asian FPV strain group) than those of European and American origin (European and American FPV strain group). Furthermore, 12 mutation sites of the VP2 protein were found in these FPV strains, of which 91 and 232 amino acid sites were previously reported. Moreover, the 91 amino acid site was found to be a positive selection site with the highest dN/dS value in the selection pressure analysis. Importantly, 35 FPV strains with 91S substitution in the VP2 protein (FPV-VP2-91S strains) had formed obvious evolutionary branches in the Asian FPV strain group. The analysis of all available VP2 protein sequences of Chinese FPV strains in the GenBank database showed that the occurrence rate of FPV-VP2-91S strains had been increasing from 15.63% to 100% during 2017~2024, indicating that the FPV-VP2-91S substitution in the VP2 protein was a noteworthy molecular characteristic of the dominant FPV strains in China. These results contribute to a better understanding of their genetic evolution and renew the knowledge of FPV molecular epidemiology. Full article

(This article belongs to the Section Animal Viruses)

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39 pages, 6668 KiB

Open AccessReview

Avian Reovirus: From Molecular Biology to Pathogenesis and Control

by Islam Nour and Sujit K. Mohanty

Viruses 2024, 16(12), 1966; https://doi.org/10.3390/v16121966 - 23 Dec 2024

Viewed by 1246

Abstract

Avian reoviruses (ARVs) represent a significant economic burden on the poultry industry due to their widespread prevalence and potential pathogenicity. These viruses, capable of infecting a diverse range of avian species, can lead to a variety of clinical manifestations, most notably tenosynovitis/arthritis. While [...] Read more.

Avian reoviruses (ARVs) represent a significant economic burden on the poultry industry due to their widespread prevalence and potential pathogenicity. These viruses, capable of infecting a diverse range of avian species, can lead to a variety of clinical manifestations, most notably tenosynovitis/arthritis. While many ARV strains are asymptomatic, pathogenic variants can cause severe inflammation and tissue damage in organs such as the tendons, heart, and liver. In broilers and turkeys, ARVs can induce severe arthritis/tenosynovitis, characterized by swollen hock joints and lesions in the gastrocnemius tendons. Additionally, ARVs have been implicated in other diseases, although their precise role in these conditions remains to be fully elucidated. In recent years, ARV cases have surged in the United States, emphasizing the need for effective control measures. Routine vaccination with commercial or autogenous vaccines is currently the primary strategy for mitigating ARV’s impact. Future research efforts should focus on enhancing our understanding of ARV-induced pathogenesis, identifying host factors that influence disease severity, and developing novel vaccines based on ongoing surveillance of circulating ARV strains. This review aims to explore the molecular aspects of ARV, including virus structure, replication, molecular epidemiology, the roles of its encoded proteins in host pathogenesis, and the immune response to ARV infection. Furthermore, we discuss the diagnostic approaches of avian reovirus and the potential biosecurity measures and vaccination trials in combating ARV and developing effective antiviral strategies. Full article

(This article belongs to the Special Issue Avian Reovirus)

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28 pages, 1741 KiB

Open AccessReview

Viral Oncogenesis: Synergistic Role of Genome Integration and Persistence

by Simone La Frazia, Silvia Pauciullo, Verdiana Zulian and Anna Rosa Garbuglia

Viruses 2024, 16(12), 1965; https://doi.org/10.3390/v16121965 - 23 Dec 2024

Viewed by 1033

Abstract

Persistence is a strategy used by many viruses to evade eradication by the immune system, ensuring their permanence and transmission within the host and optimizing viral fitness. During persistence, viruses can trigger various phenomena, including target organ damage, mainly due to an inflammatory [...] Read more.

Persistence is a strategy used by many viruses to evade eradication by the immune system, ensuring their permanence and transmission within the host and optimizing viral fitness. During persistence, viruses can trigger various phenomena, including target organ damage, mainly due to an inflammatory state induced by infection, as well as cell proliferation and/or immortalization. In addition to immune evasion and chronic inflammation, factors contributing to viral persistence include low-level viral replication, the accumulation of viral mutants, and, most importantly, maintenance of the viral genome and reliance on viral oncoprotein production. This review focuses on the process of genome integration, which may occur at different stages of infection (e.g., HBV), during the chronic phase of infection (e.g., HPV, EBV), or as an essential part of the viral life cycle, as seen in retroviruses (HIV, HTLV-1). It also explores the close relationship between integration, persistence, and oncogenesis. Several models have been proposed to describe the genome integration process, including non-homologous recombination, looping, and microhomology models. Integration can occur either randomly or at specific genomic sites, often leading to genome destabilization. In some cases, integration results in the loss of genomic regions or impairs the regulation of oncogene and/or oncosuppressor expression, contributing to tumor development. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Clinical Manifestations of Persistent Viral Infections)

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14 pages, 2324 KiB

Open AccessArticle

A Subunit Vaccine Harboring the Fusion Capsid Proteins of Porcine Circovirus Types 2, 3, and 4 Induces Protective Immune Responses in a Mouse Model

by Qikai Wang, Ran Zhang, Yue Wang, Ying Wang, Libin Liang, Haili Ma, Haidong Wang, Longlong Si and Xingchen Wu

Viruses 2024, 16(12), 1964; https://doi.org/10.3390/v16121964 - 23 Dec 2024

Viewed by 639

Abstract

Coinfections with porcine circovirus types 2, 3, and 4 (PCV2, PCV3, and PCV4) are increasingly being detected in the swine industry. However, there is no commercially available vaccine which prevents coinfection with PCV2, PCV3, and PCV4. The development of a vaccine expressing capsid [...] Read more.

Coinfections with porcine circovirus types 2, 3, and 4 (PCV2, PCV3, and PCV4) are increasingly being detected in the swine industry. However, there is no commercially available vaccine which prevents coinfection with PCV2, PCV3, and PCV4. The development of a vaccine expressing capsid (Cap) fusion proteins of multiple PCVs represents a promising approach for broadly preventing infection with PCVs. In this study, we developed a PCV subunit vaccine candidate (Cap 2-3-4) by predicting, screening, and fusing antigenic epitopes of Cap proteins of PCV2, PCV3, and PCV4. Immunoprotection assays showed that the prokaryotic expression of Cap 2-3-4 could effectively induce high levels of PCV2, PCV3, and PCV4 Cap-specific antibodies and successfully neutralize both PCV2 and PCV3. Furthermore, Cap 2-3-4 demonstrated a potent ability to activate cellular immunity and thus prevent lung damage in mice. This study provides a new option for the development of broad vaccines against PCVs. Full article

(This article belongs to the Special Issue Broadly Protective Anti-Viral Vaccines 2025)

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9 pages, 491 KiB

Open AccessCase Report

Investigation of an Outbreak of Equine Herpesvirus-1 Myeloencephalopathy in a Population of Aged Working Equids

by Nicola Pusterla, Kaila Lawton, Samantha Barnum, Kelly Ross and Kris Purcell

Viruses 2024, 16(12), 1963; https://doi.org/10.3390/v16121963 - 21 Dec 2024

Viewed by 799

Abstract

The objective of this study was to describe an outbreak of equine herpesvirus-1 myeloencephalopathy (EHM) in a population of aged equids. The outbreak was linked to the introduction of five healthy non-resident horses 15 days prior to the first case of acute recumbency. [...] Read more.

The objective of this study was to describe an outbreak of equine herpesvirus-1 myeloencephalopathy (EHM) in a population of aged equids. The outbreak was linked to the introduction of five healthy non-resident horses 15 days prior to the first case of acute recumbency. This fulminant EHM outbreak was predisposed by the grouping of the 33 unvaccinated animals in two large pens with shared water and feed troughs. Fourteen horses (42.4%) developed neurological deficits within the first week of the outbreak. Four additional equids developed fever and respiratory signs (EHV-1 infection), while fifteen horses remained healthy. EHM was supported by the detection of EHV-1 N₇₅₂ in blood (n = 11) and/or nasal secretions (9). Three out of four equids with EHV-1 infection and two out of fifteen healthy horses tested qPCR-positive for EHV-1. All animals were managed in the field. EHM and EHV-1 equids were treated with a combination of antiherpetic, anti-inflammatory, and antithrombotic drugs. Six out of fourteen EHM horses (42.9%) were euthanized because of recumbence and the inability to stand with assistance or vestibular signs. Anti-EHV-1 total IgG and IgG 4/7 levels in acute serum samples showed no significant difference amongst the three disease groups (p > 0.05); however, antibody levels rose significantly between acute and convalescent serum samples for EHM (p = 0.0001) and EHV-1 equids (p = 0.02). This outbreak highlights a very high EHM attack and fatality rate in a population of aged equids and rapid spread of EHV-1, as the population shared common pens and feeding practices. The outbreak also showed that EHM cases can be managed in the field when referral to a hospital is not an option. Full article

(This article belongs to the Section Animal Viruses)

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8 pages, 3259 KiB

Open AccessCase Report

SARS-CoV-2 Infection of the Central Nervous System: A Case Report

by Trifon Valkov, Radka Argirova and George Dimitrov

Viruses 2024, 16(12), 1962; https://doi.org/10.3390/v16121962 - 21 Dec 2024

Viewed by 871

Abstract

Central nervous system (CNS) infections caused by SARS-CoV-2 are uncommon. This case report describes the clinical progression of a 92-year-old female who developed a persistent neuroinfection associated with SARS-CoV-2. The patient initially presented with progressive fatigue, catarrhal symptoms, and a fever (38.6 °C). [...] Read more.

Central nervous system (CNS) infections caused by SARS-CoV-2 are uncommon. This case report describes the clinical progression of a 92-year-old female who developed a persistent neuroinfection associated with SARS-CoV-2. The patient initially presented with progressive fatigue, catarrhal symptoms, and a fever (38.6 °C). Initial laboratory findings revealed hypoxemia (O₂ saturation 79.8%), acidosis (pH 7.3), an elevated C-reactive protein (CRP) level of 14.8 mg/L, and a high D-dimer level (2.15 µg/mL). Nasopharyngeal (NP) antigen and RT-PCR tests confirmed SARS-CoV-2 infection, and an NP swab also detected penicillin- and ampicillin-resistant Staphylococcus aureus. She was admitted for conservative management, including oxygen supplementation, IV fluids, and prophylactic anticoagulation. Subsequently, she developed neurological symptoms—lethargy, discoordination, and impaired communication—without signs of meningism. Cerebrospinal fluid (CSF) analysis identified SARS-CoV-2 RNA (Ct = 29) on RT-PCR, while bacterial cultures remained negative. Treatment was intensified to include 10% mannitol, dexamethasone, and empiric ceftriaxone. Despite these interventions, the patient remained somnolent, with a Glasgow Coma Scale (GCS) score of 10. Upon discharge, her GCS had improved to 14; however, she continued to experience lethargy and cognitive issues, commonly described as “brain fog”. Inflammatory markers remained elevated (CRP 23 mg/L) and repeat RT-PCR of CSF confirmed a persistent SARS-CoV-2 presence (Ct = 31). This case underscores the potential for SARS-CoV-2 to cause prolonged CNS involvement, leading to persistent neurological impairment despite standard therapy. Further research is essential to clarify the pathophysiology of and determine optimal management for SARS-CoV-2 neuroinfections. Full article

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

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15 pages, 3711 KiB

Open AccessArticle

Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus Infection

by Stefan Weinberger, Carmen Stecher, Marie-Theres Kastner, Sergei Nekhai and Christoph Steininger

Viruses 2024, 16(12), 1961; https://doi.org/10.3390/v16121961 - 21 Dec 2024

Viewed by 802

Abstract

Protein phosphorylation is a crucial regulatory mechanism in cellular homeostasis. The human cytomegalovirus (HCMV) incorporates protein phosphatase 1 (PP1) into its tegument, yet the biological relevance and mechanisms of this incorporation remain unclear. Our study offers the first characterization of the PP1 interactome [...] Read more.

Protein phosphorylation is a crucial regulatory mechanism in cellular homeostasis. The human cytomegalovirus (HCMV) incorporates protein phosphatase 1 (PP1) into its tegument, yet the biological relevance and mechanisms of this incorporation remain unclear. Our study offers the first characterization of the PP1 interactome during HCMV infection and its alterations. Using co-immunoprecipitation, mass spectrometry, and quantitative proteomics, we identified 159 high-confidence interacting proteins (HCIPs) in the PP1 interactome, consisting of 126 human and 33 viral proteins. We observed significant temporal changes in the PP1 interactome following HCMV infection, including the altered interactions of PP1 regulatory subunits. Further analysis highlighted the central roles of these PP1 interacting proteins in intracellular trafficking, with particular emphasis on the trafficking protein particle complex and Rab GTPases, which are crucial for the virus’s manipulation of host cellular processes in virion assembly and egress. Additionally, our study on the noncatalytic PP1 inhibitor 1E7-03 revealed a decrease in PP1’s interaction with key HCMV proteins, supporting its potential as an antiviral agent. Our findings suggest that PP1 docking motifs are critical in viral–host interactions and offer new insights for antiviral strategies. Full article

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

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11 pages, 1586 KiB

Open AccessArticle

Plasma Interleukin-35 Levels Predict the Prognosis in Patients with HBV-Related Acute-on-Chronic Liver Failure

by Liujuan Ji, Xue Mei, Wei Yuan, Hongying Guo, Yuyi Zhang, Zhengguo Zhang, Ying Zou, Yu Liu, Hui Zhu, Zhiping Qian and Yinzhong Shen

Viruses 2024, 16(12), 1960; https://doi.org/10.3390/v16121960 - 20 Dec 2024

Viewed by 677

Abstract

This study aimed to investigate the impact of IL-35 on the prognosis of patients with HBV-ACLF. We recruited 69 patients with HBV-ACLF, 20 patients with chronic hepatitis B (CHB), 17 patients with liver cirrhosis (LC), and 20 healthy controls (HCs) from a regional [...] Read more.

This study aimed to investigate the impact of IL-35 on the prognosis of patients with HBV-ACLF. We recruited 69 patients with HBV-ACLF, 20 patients with chronic hepatitis B (CHB), 17 patients with liver cirrhosis (LC), and 20 healthy controls (HCs) from a regional infectious disease treatment center in China. Plasma levels of IL-35 at baseline were detected using ELISA. Plasma IL-35 levels in the HBV-ACLF group were the highest among all four groups. Furthermore, survivors exhibited significantly higher IL-35 levels than non-survivors (p < 0.001). IL-35 levels correlated with MELD (r = −0.678, p < 0.001), COSSH-ACLF IIs (r = −0.581, p < 0.001), alpha-fetoprotein (AFP) (r = 0.433, p < 0.001), creatinine (Cr) (r =−0.396, p = 0.001), and lactate (r =−0.38, p =0.001). The combination of plasma IL-35 and MELD score had the highest mortality prediction efficiency, with an area under the curve (AUC) of 0.895 (95% CI: 0.812–0.978, p < 0.001), a sensitivity of 80.6%, and a specificity of 93.9%. Additionally, the Kaplan–Meier analysis revealed that lower levels of IL-35 (≤191.5pg/mL) were associated with poorer survival rates in HBV-ACLF patients (p < 0.001). Our results demonstrated that IL-35 could be an effective predictive marker for the prognosis of HBV-ACLF and improve the predictive performance when combined with the MELD score. Full article

(This article belongs to the Special Issue Hepatitis Viral Infections, Pathogenesis and Therapeutics)

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13 pages, 952 KiB

Open AccessArticle

Postural Abnormalities in Children with Congenital Zika Syndrome-Related Neurological and Visual Impairment

by Raíne Borba, Amanda Rodrigues, Camila V. Ventura, Cláudia Marques, Lucélia Nóbrega, Taciana Higino, Dalmir Santos, Juliana Sallum and Liana O. Ventura

Viruses 2024, 16(12), 1959; https://doi.org/10.3390/v16121959 - 20 Dec 2024

Viewed by 588

Abstract

Deformities, body asymmetries, and muscle contractures are common consequences of atypical postural patterns in children with c ongenital Zika syndrome (CZS). This study aimed to evaluate the posture of children with CZS, considering their neurological and visual impairments. Ophthalmological assessment included binocular best-corrected [...] Read more.

Deformities, body asymmetries, and muscle contractures are common consequences of atypical postural patterns in children with c ongenital Zika syndrome (CZS). This study aimed to evaluate the posture of children with CZS, considering their neurological and visual impairments. Ophthalmological assessment included binocular best-corrected visual acuity (BCVA) using Teller Acuity Cards II (TAC II) and an ocular motility evaluation. Postural alignment was measured using the PhysioCode Posture (PCP) app. Twenty-four children with CZS (12 [50.0%] female) were included, with a mean age of 6.8 ± 0.7 years (range, 4.0–7.0 years). The majority (79.2% [19/24]) had microcephaly at birth. Visual impairment was detected in 95.2% (20/21) of the children, with 85.0% (17/20) classified as moderate, severe, or blind. Shoulder asymmetry was observed in 95.8% (23/24) of participants, and 75.0% (18/24) presented abnormal postural alignment of the head and hips. Additionally, spinal deviations were found in 41.7% (10/24) of the children. All children with CZS exhibited asymmetries and improper postural patterns, which may result from a combination of neurological and visual impairments as well as environmental factors. Full article

(This article belongs to the Special Issue Mosquito-Borne Encephalitis Viruses)

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14 pages, 2126 KiB

Open AccessBrief Report

Optimized Directed Virus Evolution to Accelerate the Generation of Oncolytic Coxsackievirus B3 Adapted to Resistant Colorectal Cancer Cells

by Leslie Elsner, Babette Dieringer, Anja Geisler, Maxim Girod, Sophie Van Linthout, Jens Kurreck and Henry Fechner

Viruses 2024, 16(12), 1958; https://doi.org/10.3390/v16121958 - 20 Dec 2024

Viewed by 629

Abstract

Recently, we demonstrated that the oncolytic Coxsackievirus B3 (CVB3) strain PD-H can be efficiently adapted to resistant colorectal cancer cells through dose-dependent passaging in colorectal cancer cells. However, the method is time-consuming, which limits its clinical applicability. Here, we investigated whether the manufacturing [...] Read more.

Recently, we demonstrated that the oncolytic Coxsackievirus B3 (CVB3) strain PD-H can be efficiently adapted to resistant colorectal cancer cells through dose-dependent passaging in colorectal cancer cells. However, the method is time-consuming, which limits its clinical applicability. Here, we investigated whether the manufacturing time of the adapted virus can be reduced by replacing the dose-based passaging with volume-based passaging. For this purpose, the murine colorectal carcinoma cell line MC38, resistant to PD-H-induced lysis, was initially infected with PD-H at 0.1 multiplicity of infection (MOI). For subsequent passages, 15–30 µL of a 1:10 dilution of the cell culture supernatant was transferred to fresh MC38 cells early after virus-induced cell lysis became visible. By virus passage 10, complete cell lysis of MC38 cells was achieved. Sequencing of the passage 10 virus (P-10) revealed two nucleotide substitutions in the 5′ UTR and six amino acid changes in the viral polyprotein compared to the PD-H founder. P-10, however, consisted of a heterogeneous virus population. Therefore, the detected mutations were introduced into the cDNA of PD-H, from which the recombinant virus PD-MC38 was generated. PD-MC38 exhibited significantly enhanced replication and lytic activity in MC38 cells compared to PD-H, whereas its oncolytic activity in other colorectal cancer cell lines was comparable to or even lower than that of PD-H. These findings demonstrate that volume-based passaging is suitable to generate tumor cell-specific adapted PD-H. Moreover, compared to the dose-dependent passaging, volume-based passaging significantly reduced the time required to generate the adapted virus. Full article

(This article belongs to the Section General Virology)

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15 pages, 1044 KiB

Open AccessArticle

High-Throughput Sequencing for the Detection of Viruses in Grapevine: Performance Analysis and Best Practices

by Kristian A. Stevens and Maher Al Rwahnih

Viruses 2024, 16(12), 1957; https://doi.org/10.3390/v16121957 - 20 Dec 2024

Viewed by 528

Abstract

Among the cultivated crop species, the economically and culturally important grapevine plays host to the greatest number of distinctly characterized viruses. A critical component of the management and containment of these viral diseases in grapevine is both the identification of infected vines and [...] Read more.

Among the cultivated crop species, the economically and culturally important grapevine plays host to the greatest number of distinctly characterized viruses. A critical component of the management and containment of these viral diseases in grapevine is both the identification of infected vines and the characterization of new pathogens. Next-generation high-throughput sequencing technologies, i.e., HTS technologies, have been widely adopted for their ability to quickly, broadly and directly characterize molecular sequences associated with potential pathogens. We empirically analyze the performance of HTS as a diagnostic tool in a phytosanitary context and make recommendations on its deployment for detecting known and novel viruses in grapevine. Three popular and widely used modalities for analyzing HTS data are characterized and compared using the standard diagnostic performance criteria of sensitivity (the true positive rate), specificity (the true negative rate) and analytical sensitivity (dilution series). Full article

(This article belongs to the Special Issue Advances in Plant Virus/Viroid Detection and Identification Methods)

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15 pages, 6418 KiB

Open AccessArticle

Phylogenetic and Pathogenic Analysis of H5N1 and H5N6 High Pathogenicity Avian Influenza Virus Isolated from Poultry Farms (Layer and Broiler Chickens) in Japan in the 2023/2024 Season

by Hayate Nishiura, Asuka Kumagai, Junki Mine, Yoshihiro Takadate, Saki Sakuma, Ryota Tsunekuni, Yuko Uchida and Kohtaro Miyazawa

Viruses 2024, 16(12), 1956; https://doi.org/10.3390/v16121956 - 20 Dec 2024

Viewed by 929

Abstract

During the 2023–2024 winter, 11 high pathogenicity avian influenza (HPAI) outbreaks caused by clade 2.3.4.4b H5N1 and H5N6 HPAI viruses were confirmed in Japanese domestic poultry among 10 prefectures (n = 10 and 1, respectively). In this study, we aimed to genetically [...] Read more.

During the 2023–2024 winter, 11 high pathogenicity avian influenza (HPAI) outbreaks caused by clade 2.3.4.4b H5N1 and H5N6 HPAI viruses were confirmed in Japanese domestic poultry among 10 prefectures (n = 10 and 1, respectively). In this study, we aimed to genetically and pathologically characterize these viruses. Phylogenetic analysis revealed that H5N1 viruses were classified into the G2d-0 genotype, whereas the H5N6 virus was a novel genotype in Japan, designated as G2c-12. The G2c-12 virus shared PB2, PB1, PA, HA, and M genes with previous G2c viruses, but had NP and NS genes originating from avian influenza viruses in wild birds abroad. The N6 NA gene was derived from an H5N6 HPAI virus that was different from the viruses responsible for the outbreaks in Japan in 2016–2017 and 2017–2018. Experimental infections in chickens infected with H5N1(G2d-0) and H5N6(G2c-12) HPAI viruses showed no significant differences in the 50% chicken lethal dose, mean death time, or virus shedding from the trachea and cloaca, or in the histopathological findings. Different genotypes of the viruses worldwide, their introduction into the country, and their stable lethality in chickens may have triggered the four consecutive seasons of HPAI outbreaks in Japan. Full article

(This article belongs to the Section Animal Viruses)

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11 pages, 730 KiB

Open AccessArticle

Persistence of Long COVID Symptoms Two Years After SARS-CoV-2 Infection: A Prospective Longitudinal Cohort Study

by Gili Joseph, Ili Margalit, Yael Weiss-Ottolenghi, Carmit Rubin, Havi Murad, Raquel C. Gardner, Noam Barda, Elena Ben-Shachar, Victoria Indenbaum, Mayan Gilboa, Sharon Alroy-Preis, Yitshak Kreiss, Yaniv Lustig and Gili Regev-Yochay

Viruses 2024, 16(12), 1955; https://doi.org/10.3390/v16121955 - 20 Dec 2024

Viewed by 954

Abstract

Background/Objectives: Millions of individuals worldwide continue to experience symptoms following SARS-CoV-2 infection. This study aimed to assess the prevalence and phenotype of multi-system symptoms attributed to Long COVID—including fatigue, pain, cognitive-emotional disturbances, headache, cardiopulmonary issues, and alterations in taste and smell—that have persisted [...] Read more.

Background/Objectives: Millions of individuals worldwide continue to experience symptoms following SARS-CoV-2 infection. This study aimed to assess the prevalence and phenotype of multi-system symptoms attributed to Long COVID—including fatigue, pain, cognitive-emotional disturbances, headache, cardiopulmonary issues, and alterations in taste and smell—that have persisted for at least two years after acute infection, which we define as “persistent Long COVID”. Additionally, the study aimed to identify clinical features and blood biomarkers associated with persistent Long COVID symptoms. Methods: We sent a detailed long COVID symptoms questionnaire to an existing cohort of 1258 vaccinated adults (age 18–79 years) who had mild infection (e.g., non-hospitalized) SARS-CoV-2 Delta variant 2 years earlier. These individuals had comprehensive datasets, including blood samples, available for further analysis. We estimated prevalence of persistent long COVID two years post-infection using weighted adjustment (Horvitz–Thompson estimator) to overcome reporting bias. Multivariable logistic regression models were used to determine association of clinical features and blood biomarkers (pre-infection SARS-CoV-2 RBD-IgG, SARS-CoV-2 neutralizing antibodies, and pre-infection and post-infection neurofilament light) with prevalence of persistent long COVID. Results: N = 323 participants responded to the survey, of whom N = 74 (23%) reported at least one long COVID symptom that had persisted for two years after the acute infection. Weighted prevalence of persistent long COVID symptoms was 21.5% (95% CI = 16.7–26.3%). Female gender, smoking, and severity of acute COVID-19 infection were significantly associated with persistent Long COVID. The blood biomarkers assessed were not significantly associated with persistent Long COVID. Conclusions: Among vaccinated adults two years after mild infection with Delta variant SARS-CoV-2, persistent symptoms attributed to Long COVID are extremely common, certain subgroups are at higher risk, and further research into biological mechanisms and potential treatment targets is needed. Full article

(This article belongs to the Special Issue Beyond Acute: Navigating Long COVID and Post-Viral Complications)

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13 pages, 1354 KiB

Open AccessPerspective

The Temporal Order of Mixed Viral Infections Matters: Common Events That Are Neglected in Plant Viral Diseases

by Celia de Moya-Ruiz, Inmaculada Ferriol and Pedro Gómez

Viruses 2024, 16(12), 1954; https://doi.org/10.3390/v16121954 - 20 Dec 2024

Viewed by 722

Abstract

Mixed infections of plant viruses are common in crops and represent a critical biotic factor with substantial epidemiological implications for plant viral diseases. Compared to single-virus infections, mixed infections arise from simultaneous or sequential infections, which can inevitably affect the ecology and evolution [...] Read more.

Mixed infections of plant viruses are common in crops and represent a critical biotic factor with substantial epidemiological implications for plant viral diseases. Compared to single-virus infections, mixed infections arise from simultaneous or sequential infections, which can inevitably affect the ecology and evolution of the diseases. These infections can either exacerbate or ameliorate symptom severity, including virus–virus interactions within the same host that may influence a range of viral traits associated with disease emergence. This underscores the need for a more comprehensive understanding of how the order of virus arrival to the host can impact plant disease dynamics. From this perspective, we reviewed the current evidence regarding the impact of mixed infections within the framework of simultaneous and sequential infections in plants, considering the mode of viral transmission. We also examined how the temporal order of mixed infections could affect the dynamics of viral populations and present a case study of two aphid-transmitted viruses infecting melon plants, suggesting that the order of virus arrival significantly affects viral load and disease outcomes. Finally, we anticipate future research that reconciles molecular epidemiology and evolutionary ecology, underlining the importance of biotic interactions in shaping viral epidemiology and plant disease dynamics in agroecosystems. Full article

(This article belongs to the Special Issue Plant Viruses and Their Vectors: Epidemiology and Control)

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16 pages, 2300 KiB

Open AccessArticle

Genetic Diversity and Antiretroviral Resistance in HIV-1-Infected Patients Newly Diagnosed in Cabo Verde

by Silvânia Da Veiga Leal, Victor Pimentel, Paloma Gonçalves, Isabel Inês Monteiro de Pina Araújo, Ricardo Parreira, Nuno Taveira, Marta Pingarilho and Ana B. Abecasis

Viruses 2024, 16(12), 1953; https://doi.org/10.3390/v16121953 - 20 Dec 2024

Viewed by 802

Abstract

The high genetic variability of HIV-1 and the emergence of transmitted drug resistance (TDR) can impact treatment efficacy. In this study, we investigated the prevalent HIV-1 genotypes and drug-resistance-associated mutations in drug-naïve HIV-1 individuals in Cabo Verde. The study, conducted between 2018 and [...] Read more.

The high genetic variability of HIV-1 and the emergence of transmitted drug resistance (TDR) can impact treatment efficacy. In this study, we investigated the prevalent HIV-1 genotypes and drug-resistance-associated mutations in drug-naïve HIV-1 individuals in Cabo Verde. The study, conducted between 2018 and 2019, included drug-naïve HIV-1 individuals from the São Vicente, Boa Vista, Fogo, and Santiago islands. The HIV-1 pol gene was sequenced using Sanger sequencing. TDR was identified using the Stanford Calibrated Population Resistance tool, and resistance levels to different drugs were interpreted with the Stanford HIV database. The genetic diversity of HIV-1 was determined through phylogenetic analysis, and epidemiological and behavioural data were collected via questionnaires. Of the 73 participants, the majority were male (52.1%). The CRF02_AG recombinant form predominated (41.1%), followed by subtype G (37.0%). The overall prevalence of TDR was 9.6%. Nucleoside Reverse Transcriptase Inhibitor (NRTI) mutations occurred in 2.7% of individuals, while Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) mutations occurred in 9.6%. The most prevalent mutations were K103N (5.5%) and M184V (2.7%). No protease- or integrase-associated mutations were found. The high levels of resistance to NNRTIs found demonstrate the need for surveillance of resistance mutations to ensure the efficacy and durability of the current therapeutic regimen, which includes Dolutegravir. Full article

(This article belongs to the Special Issue The Challenge of HIV Diversity)

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16 pages, 1748 KiB

Open AccessArticle

Influenza Virus Surveillance from the 1918 Influenza Pandemic to the 2020 Coronavirus Pandemic in New York State, USA

by Kay L. Escuyer, Donna L. Gowie and Kirsten St. George

Viruses 2024, 16(12), 1952; https://doi.org/10.3390/v16121952 - 20 Dec 2024

Viewed by 796

Abstract

A historical perspective of more than one hundred years of influenza surveillance in New York State demonstrates the progression from anecdotes and case counts to next-generation sequencing and electronic database management, greatly improving pandemic preparedness and response. Here, we determined if influenza virologic [...] Read more.

A historical perspective of more than one hundred years of influenza surveillance in New York State demonstrates the progression from anecdotes and case counts to next-generation sequencing and electronic database management, greatly improving pandemic preparedness and response. Here, we determined if influenza virologic surveillance at the New York State public health laboratory (NYS PHL) tests sufficient specimen numbers within preferred confidence limits to assess situational awareness and detect novel viruses that pose a pandemic risk. To this end, we analyzed retrospective electronic data on laboratory test results for the influenza seasons 1997–1998 to 2021–2022 according to sample sizes recommended in the Influenza Virologic Surveillance Right Size Roadmap issued by the Association of Public Health Laboratories and Centers for Disease Control and Prevention. Although data solely from specimens submitted to the NYS PHL were insufficient to meet surveillance goals, when supplemented with testing data from clinical laboratories participating in surveillance programs, the recommended surveillance goals were achieved. Despite the sudden decline in influenza cases in 2020–2021, impacted by the COVID-19 mitigation measures, the dramatic increases in influenza cases surrounding the coronavirus pandemic reveal that influenza remains a national and international public health threat. Sample submissions to public health laboratories must be encouraged to facilitate monitoring for emerging viruses and preparedness for another pandemic. Full article

(This article belongs to the Special Issue Impact of Pandemic Measures on the Epidemiology and Seasonality of Other Viruses)

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16 pages, 4757 KiB

Open AccessArticle

A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo Viruses

by Qinglin Kang, Gege Li, Yan Wu, Shaoyan Wang, Zhengshan Chen, Xiaodong Zai, Xiaoyan Pan, Rong Wang, Jiansheng Lu, Peng Du, Zhixin Yang, Xiangyang Chi, Gengfu Xiao and Junjie Xu

Viruses 2024, 16(12), 1951; https://doi.org/10.3390/v16121951 - 20 Dec 2024

Viewed by 991

Abstract

The Junín virus (JUNV) is one of the New World arenaviruses that cause severe hemorrhagic fever. Human transferrin receptor 1 (hTfR1) has been identified as the main receptor for JUNV for virus entry into host cells. To date, no treatment has been approved [...] Read more.

The Junín virus (JUNV) is one of the New World arenaviruses that cause severe hemorrhagic fever. Human transferrin receptor 1 (hTfR1) has been identified as the main receptor for JUNV for virus entry into host cells. To date, no treatment has been approved for JUNV. Herein, we investigated 12 anti-hTfR1 VHH (variable domain of the heavy chain of heavy-chain antibody) antibodies and confirmed their interaction with hTfR1. Most of them could bind to the hTfR1 apical domain, which is the glycoprotein 1 (GP1) binding domain of JUNV. Among them, 18N18 exhibited neutralizing activity against both the human immunodeficiency virus (HIV)-vectored lentiviral Junín pseudoviruses and the recombinant vesicular stomatitis virus (VSV)-vectored Junín pseudoviruses. We also verified that 18N18 blocked the interaction between hTfR1 and JUNV GP1. In addition, 18N18 could neutralize another New World arenavirus, the Machupo virus. Using AlphaFold 3-based simulation of 18N18–hTfR1 docking, we determined that 18N18’s binding epitope was located at the JUNV GP1 binding epitope. 18N18 represents a candidate for JUNV treatment and provides a potential approach that could be applied to New World arenaviruses. Full article

(This article belongs to the Special Issue B Cell-Mediated Immunity to Viruses)

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14 pages, 932 KiB

Open AccessArticle

High Detection Rate of Rotavirus Infection Among Children Admitted with Acute Gastroenteritis to Six Public Hospitals in Luanda Province After the Introduction of Rotarix^® Vaccine: A Cross-Sectional Study

by Dikudila Vita, Manuel Lemos, Zoraima Neto, Mathebula Evans, Ngiambudulu M. Francisco, Filomeno Fortes, Ema Fernandes, Celso Cunha and Claudia Istrate

Viruses 2024, 16(12), 1949; https://doi.org/10.3390/v16121949 - 20 Dec 2024

Viewed by 844

Abstract

Rotavirus group A (RVA) is a major cause of pediatric acute gastroenteritis (AGE). Vaccination is an effective public health strategy and Angola implemented it in 2014. This hospital-based study aimed to estimate the prevalence of RVA infection and the severity of AGE in [...] Read more.

Rotavirus group A (RVA) is a major cause of pediatric acute gastroenteritis (AGE). Vaccination is an effective public health strategy and Angola implemented it in 2014. This hospital-based study aimed to estimate the prevalence of RVA infection and the severity of AGE in children under five years of age treated at six hospitals in Luanda Province. Between April 2021 and May 2022, 1251 fecal samples were screened by an immunochromatographic rapid test (SD Bioline). Data on socio-demographic profile, nutritional status, and clinical assessment were obtained. The association of RVA infection and AGE severity with possible risk factors was evaluated with a binary logistic regression model. Overall, the detection rate was 57.8% and girls tend to be more often infected than boys (55.2%). Infection was more common in the youngest group (1 to 6 months, 60.3%). Important sources of RVA infection were drinking water kept in tanks (57.9%) and private sanitary facilities with piped water (61%). Surprisingly, according to the Vesikari Scale score, the most severe symptoms were observed in children vaccinated with two doses (80.7%). RVA prevalence remains high despite vaccination, and further studies should address the association between infection sources and disease severity, as well as the causes underlying vaccine (un)effectiveness. Full article

(This article belongs to the Special Issue The 9th Edition of the European Rotavirus Biology Meeting (ERBM-9))

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12 pages, 1157 KiB

Open AccessArticle

Performance of Ultrasensitive Polymerase Chain Reaction Testing for JC Polyomavirus in Cerebrospinal Fluid Compared with Pathological Diagnosis of Progressive Multifocal Leukoencephalopathy

by Kenta Takahashi, Kazuo Nakamichi, Yuko Sato, Harutaka Katano, Hideki Hasegawa, Masayuki Saijo and Tadaki Suzuki

Viruses 2024, 16(12), 1950; https://doi.org/10.3390/v16121950 - 19 Dec 2024

Viewed by 596

Abstract

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the JC polyomavirus (JCPyV). Based on the clinical criteria, PML is diagnosed via polymerase chain reaction (PCR) detection of JCPyV DNA in cerebrospinal fluid (CSF) in combination with neurological and imaging findings. Although [...] Read more.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the JC polyomavirus (JCPyV). Based on the clinical criteria, PML is diagnosed via polymerase chain reaction (PCR) detection of JCPyV DNA in cerebrospinal fluid (CSF) in combination with neurological and imaging findings. Although the utility of CSF JCPyV testing using ultrasensitive PCR assays has been suggested, its potential requires further evaluation. This study retrospectively analyzed the detection performance of ultrasensitive PCR for CSF JCPyV in patients who underwent brain tissue examination based on the pathological diagnostic criteria for PML. Of the 110 patients with pathologically confirmed definite PML or not PML, standard and ultrasensitive CSF testing was performed for 36 and 74 patients, respectively. The sensitivity of ultrasensitive CSF JCPyV testing of the initial specimens was 85%. With the addition of the follow-up testing, this figure increased to 95%. The specificity and false-positive rate of ultrasensitive CSF JCPyV testing, including follow-up, were 100% and 0%, respectively. No statistically significant correlation was observed between CSF and brain JCPyV levels. The results of this study demonstrate the high sensitivity and accuracy of ultrasensitive CSF JCPyV testing and provide essential information for the clinical diagnosis of PML. Full article

(This article belongs to the Special Issue JC Polyomavirus)

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13 pages, 2458 KiB

Open AccessArticle

Detection of DNA Viruses in Free-Ranging Rat Populations in Hungary

by Márton Z. Vidovszky, András Surján, Gábor Földvári and László Egyed

Viruses 2024, 16(12), 1948; https://doi.org/10.3390/v16121948 - 19 Dec 2024

Viewed by 612

Abstract

To address a gap in our understanding of viral infections in epidemiologically important rat species, we aimed to detect DNA viruses from the tissues of free-ranging rat populations in Hungary. DNA viruses were identified from the parenchymal organs of 230 Rattus norvegicus and [...] Read more.

To address a gap in our understanding of viral infections in epidemiologically important rat species, we aimed to detect DNA viruses from the tissues of free-ranging rat populations in Hungary. DNA viruses were identified from the parenchymal organs of 230 Rattus norvegicus and Rattus rattus, using family-specific pan-PCR assays followed by sequencing of the PCR products. Adeno-, herpes-, circo-, and polyomaviruses were detected, while irido-, pox-, and dependoparvoviruses were not. Adenovirus DNA was present in 6.5% of the samples, herpesvirus and polyomavirus DNA in 12.2%, and circovirus DNA in 1.7%. All detected herpesviruses belonged to the β and γ subfamilies, with a majority being β herpesviruses. Some adenovirus and herpesvirus sequences were novel, while only the known Rattus norvegicus polyomavirus 1 was detected for polyomaviruses. The rare circovirus-positive samples revealed the presence of both rodent and bird circoviruses, indicating the ability of circoviruses to cross species barriers. Our findings show that rats host a variety of DNA viruses, many of which were previously uncharacterized, highlighting the need for further diagnostic studies. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 3317 KiB

Open AccessArticle

Respiratory Virus-Specific and Time-Dependent Interference of Adenovirus Type 2, SARS-CoV-2 and Influenza Virus H1N1pdm09 During Viral Dual Co-Infection and Superinfection In Vitro

by Maria Alfreda Stincarelli, Rosaria Arvia, Bernardo Guidotti and Simone Giannecchini

Viruses 2024, 16(12), 1947; https://doi.org/10.3390/v16121947 - 19 Dec 2024

Viewed by 823

Abstract

Background. Understanding the interference patterns of respiratory viruses could be important for shedding light on potential strategies to combat these human infectious agents. Objective. To investigate the possible interactions between adenovirus type 2 (AdV2), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza [...] Read more.

Background. Understanding the interference patterns of respiratory viruses could be important for shedding light on potential strategies to combat these human infectious agents. Objective. To investigate the possible interactions between adenovirus type 2 (AdV2), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/H1N1 pandemic (H1N1pdm09) using the A549 cell line. Methods. Single infections, co-infections, and superinfections (at 3 and 24 h after the first virus infection) were performed by varying the multiplicity of infection (MOI). Virus replication kinetics and the mRNA expression of IFN-α, IL-1α and IL-6 were assessed by real-time qPCR. Results. Co-infection experiments showed different growth dynamics, depending on the presence of the specific virus and time. AdV2 replication remained stable or possibly enhanced in the presence of co-infection with each of the two H1N1pdm09 and SARS-CoV-2 viruses used. In contrast, SARS-CoV-2 replication was facilitated by H1N1pdm09 but hindered by AdV2, indicating possible different interactions. Finally, H1N1pdm09 replication exhibited variably effectiveness in the presence of AdV2 and SARS-CoV-2. Superinfection experiments showed that the replication of all viruses was affected by time and MOI. The mRNA expression of IFN-α, IL-1α and IL-6 showed divergent results depending on the virus used and the time of infection. Conclusions. Further investigation of co-infection or superinfection may be helpful in understanding the potential relationship involved in the outcome of viral respiratory infection in the human population. Full article

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

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11 pages, 4265 KiB

Open AccessArticle

Development of a Synthetic VP1 Protein Peptide-Based ELISA to Detect Antibodies Against Porcine Bocavirus Group 3

by Chao Gong, Hui He, Yuguang Fu, Baoyu Li, Bin Yang, Jianlong Li, Xiaodong He, Juncheng Han, Yi Zhang, Guangliang Liu and Qingyong Guo

Viruses 2024, 16(12), 1946; https://doi.org/10.3390/v16121946 - 19 Dec 2024

Viewed by 585

Abstract

Porcine bocavirus (PBoV), classified within the genus Bocaparvovirus, has been reported worldwide. PBoV has been divided into group 1, group 2, and group 3. PBoV group 3 (G3) viruses are the most prevalent in China. Currently, effective serological methods for the detection of [...] Read more.

Porcine bocavirus (PBoV), classified within the genus Bocaparvovirus, has been reported worldwide. PBoV has been divided into group 1, group 2, and group 3. PBoV group 3 (G3) viruses are the most prevalent in China. Currently, effective serological methods for the detection of antibodies against PBoV G3 are limited. In this study, we developed an indirect ELISA using a synthetic VP1 peptide designed on the basis of the conserved region of the PBoV VP1 protein as a coating antigen. Through matrix titration, the optimal coating concentration of the VP1 peptide (0.5 μg/mL), serum dilution (1:200), and working concentration of the secondary antibody (1:50,000) were determined. The cutoff value of this developed ELISA was set as 0.4239. Further investigations revealed that this developed ELISA had no cross-reactivity with positive serum antibodies against FMDV-O, FMDV-A, PRV, ASFV, SF, PCV2, PEDV, and TGEV. The detection limit of the method was a 1:1600 dilution of standard positive serum against PBoV G3. The coefficients of variation for both the intra- and interassay data were lower than 10%. A total of 1373 serum samples collected from 12 provinces in China between 2022 and 2023 were subjected to indirect ELISA. The results showed that 47.56% of the samples were PBoV G3 positive. These results reveal that peptide-based ELISA is a reliable and cost-effective method for detecting PBoV G3 antibodies. It also facilitates the investigation of the prevalence and distribution of PBoV G3. Full article

(This article belongs to the Special Issue Porcine Viruses 2024)

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20 pages, 762 KiB

Open AccessArticle

Circulating MicroRNAs Related to Arterial Stiffness in Adults with HIV Infection

by Sideris Nanoudis, Maria P. Yavropoulou, Olga Tsachouridou, Maria Pikilidou, Dimitrios Pilalas, Kalliopi Kotsa, Lemonia Skoura, Pantelis Zebekakis and Symeon Metallidis

Viruses 2024, 16(12), 1945; https://doi.org/10.3390/v16121945 - 19 Dec 2024

Viewed by 765

Abstract

People with HIV (PWH) have an elevated risk of cardiovascular disease compared to those without HIV. This study aimed to investigate the relative serum expression of microRNAs (miRNAs) associated with arterial stiffness, a significant marker of cardiovascular disease. A total of 36 male [...] Read more.

People with HIV (PWH) have an elevated risk of cardiovascular disease compared to those without HIV. This study aimed to investigate the relative serum expression of microRNAs (miRNAs) associated with arterial stiffness, a significant marker of cardiovascular disease. A total of 36 male PWH and 36 people without HIV, matched for age, body mass index, pack years, and dyslipidemia, were included in the study. Participants with a history of hypertension, diabetes mellitus, cardiovascular disease, cancer, or intravenous drug use were excluded. Markers of arterial stiffness, including carotid–femoral pulse wave velocity (cfPWV) and augmentation index adjusted to 75 beats per minute (AIx@75), were measured via applanation tonometry. We analyzed the relative expression of 11 circulating miRNAs using real-time PCR: let-7b-5p, miR-19b-3p, miR-21-5p, miR-29a-3p, miR-126-3p, miR-130a-3p, miR-145-5p, miR-181b-5p, miR-221-3p, miR-222-3p, and miR-223-3p. cfPWV was significantly higher in PWH compared to people without HIV (9.3 vs. 8.6 m/s, p = 0.019), while AIx@75, peripheral, and aortic blood pressures did not differ among groups. The relative expression of circulating miRNAs was significantly higher in PWH compared to controls for let-7b-5p (fold change: 5.24, p = 0.027), miR-21-5p (fold change: 3.41, p < 0.001), miR-126-3p (fold change: 1.23, p = 0.019), and miR-222-3p (fold change: 3.31, p = 0.002). Conversely, the relative expression of circulating miR-19b-3p was significantly lower in PWH (fold change: 0.61, p = 0.049). Among HIV-related factors, the nadir CD4+T-cell count of <200 cells/mm³ was independently associated with the relative expression of circulating let-7b-5p (β = 0.344, p = 0.049), while current non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment was independently associated with the relative expression of circulating miR-126-3p (β = 0.389, p = 0.010). No associations were found between the duration of HIV infection or the duration of ART and the serum miRNA expression. This study highlights a distinct circulating miRNA profile in PWH with higher cfPWV compared to those without HIV, which may contribute to increased arterial stiffness. Full article

(This article belongs to the Section General Virology)

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25 pages, 7460 KiB

Open AccessArticle

Human Melanoma and Glioblastoma Cells Express Cathepsins Supporting Reovirus Moscow Strain Infection

by Yulia Ammour, Eugenia Nikolaeva, Olesya Sagimbaeva, Pavel Shamsutdinov, Anastasia Astapenko, Yulia Zhelaeva, Marina Gavrilova, Olga Susova, Aleksey Mitrofanov, Ali Bekyashev, Tatiana Nasedkina, Oxana Svitich, Evgeny Faizuloev and Vitaly Zverev

Viruses 2024, 16(12), 1944; https://doi.org/10.3390/v16121944 - 19 Dec 2024

Viewed by 691

Abstract

This study evaluates the oncolytic potential of the Moscow strain of reovirus against human metastatic melanoma and glioblastoma cells. The Moscow strain effectively infects and replicates within human melanoma cell lines and primary glioblastoma cells, while sparing non-malignant human cells. Infection leads to [...] Read more.

This study evaluates the oncolytic potential of the Moscow strain of reovirus against human metastatic melanoma and glioblastoma cells. The Moscow strain effectively infects and replicates within human melanoma cell lines and primary glioblastoma cells, while sparing non-malignant human cells. Infection leads to the selective destruction of neoplastic cells, mediated by functional viral replication. A positive correlation was identified between viral RNA accumulation and tumor cell death, with no replication observed in non-malignant cells. This study highlights the critical roles of cathepsins B, L, and S as mediators of the oncolytic process. The pharmacological inhibition of these enzymes significantly attenuated reovirus-induced cytotoxicity in melanoma and glioblastoma cells. Conversely, PKR production analysis revealed minimal activation in reovirus-infected tumor cells, suggesting that the hyperactivation of the RAS-signaling pathway and subsequent PKR inhibition do not directly contribute to the selective efficacy of reovirus. Moreover, infected tumor cells exhibited features of both apoptotic and non-apoptotic death, emphasizing the intricate mechanisms of reovirus-mediated oncolysis. These findings underscore the therapeutic promise of the Moscow strain of reovirus as a selective and potent oncolytic agent for targeting melanoma and glioblastoma cells. Full article

(This article belongs to the Special Issue Progress and Prospects in Oncolytic Virotherapy)

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32 pages, 13522 KiB

Open AccessArticle

Characterization of Hepatitis B Virus Transcripts in Chronically HBV-Infected Chimpanzees and Patients Treated with ARC-520 siRNA Demonstrates Transcriptional Silencing of cccDNA

by Christine I. Wooddell, Dean Sanders, Zhao Xu, Lung-Yi Mak, Thomas Schluep, Wai-Kay Seto, Bruce D. Given and Man-Fung Yuen

Viruses 2024, 16(12), 1943; https://doi.org/10.3390/v16121943 - 19 Dec 2024

Viewed by 819

Abstract

Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts with the potential to encode HBx, HBsAg, HBeAg, core, and polymerase, [...] Read more.

Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts with the potential to encode HBx, HBsAg, HBeAg, core, and polymerase, as well as transcripts likely to be derived from dimers of dslDNA, and these differed between HBeAg-positive (HBeAg+) and HBeAg-negative (HBeAg−) individuals. HBV transcripts from the last follow-up ~30 months post-ARC-520 treatment were categorized from one HBeAg+ (one of two previously highly viremic patients that became HBeAg− upon treatment and had greatly reduced cccDNA products) and four HBeAg− patients. The previously HBeAg+ patient received a biopsy that revealed that he had 3.4 copies/cell cccDNA (two to three orders of magnitude more cccDNA than HBeAg− chimpanzees) but expressed primarily truncated X and HBsAg from iDNA, like two patients that were HBeAg− at the start of the study and had one copy/cell cccDNA. No HBV transcripts were detected in two other HBeAg− patients that had ~0.3 copies/cell cccDNA, one of which had seroconverted for HBsAg. The paucity of cccDNA-derived transcripts in the presence of high cccDNA demonstrates the transcriptional silencing of HBV following MD siRNA treatment with ETV. Full article

(This article belongs to the Special Issue HBV Transcriptional and Post-transcriptional Regulation)

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11 pages, 4549 KiB

Open AccessArticle

Immune Response to SARS-CoV-2 XBB.1.5 and JN.1 Variants Following XBB.1.5 Booster Vaccination in Liver Transplant Recipients

by Philippa von der Schulenburg, Georg M. N. Behrens, Markus Hoffmann, Alexandra Linke, Inga Nehlmeier, Amy Madeleine Kempf, Metodi Stankov, Marc Lütgehetmann, Jacqueline Jahnke-Triankowski, Marylyn M. Addo, Lutz Fischer, Ansgar W. Lohse, Stefan Pöhlmann, Julian Schulze zur Wiesch and Martina Sterneck

Viruses 2024, 16(12), 1942; https://doi.org/10.3390/v16121942 - 19 Dec 2024

Viewed by 729

Abstract

Background/Objectives: The efficacy of monovalent BNT162b2 Omicron XBB.1.5 booster vaccination in liver transplant recipients (LTRs) has yet to be described, particularly regarding the immune response to emerging variants like JN.1. Methods: This study evaluated humoral and cellular immune responses in 34 liver transplant [...] Read more.

Background/Objectives: The efficacy of monovalent BNT162b2 Omicron XBB.1.5 booster vaccination in liver transplant recipients (LTRs) has yet to be described, particularly regarding the immune response to emerging variants like JN.1. Methods: This study evaluated humoral and cellular immune responses in 34 liver transplant recipients (LTRs) with varying SARS-CoV-2 immune histories before and after receiving a BNT162b2 Omicron XBB.1.5 booster vaccination. The assessment involved variant-specific serology, pseudovirus neutralization tests, and Interferon-γ release assays. Results: Participants had a median of four prior vaccinations, with 91.2% having a history of infection. Post-vaccination, significant increases in both Wuhan anti-S and Omicron-specific IgG antibodies and improved neutralization of B.1, XBB.1.5, and JN.1 pseudovirus particles were observed. Also, T-cell responses significantly increased post-vaccination. However, 17.6% of LTRs had no neutralizing antibodies against XBB.1.5 and JN.1, while 100% of healthy controls did. Shortly after vaccination, 18% of patients developed mild COVID-19. These LTRs had particularly low immune responses at baseline. Conclusions: The monovalent XBB.1.5 booster improved overall SARS-CoV-2-specific immunity. However, some LTRs still showed low or undetectable immune responses, indicating that ongoing monitoring and further booster doses are necessary in this high-risk group. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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6 pages, 851 KiB

Open AccessBrief Report

Tracing the Dispersal Pathway of HIV-1 Subtype C to Bahia: Phylogenetic Connections to Southern Brazil

by Daniel Polita, Laise de Moraes, Marta Giovanetti, Filipe Ferreira de Almeida Rego, Luciane Amorim Santos, Dennis Maletich Junqueira and Ricardo Khouri

Viruses 2024, 16(12), 1941; https://doi.org/10.3390/v16121941 - 19 Dec 2024

Viewed by 520

Abstract

The HIV-1 epidemic in Brazil is predominantly characterized by subtype B, except in the southern states, where subtype C (HIV-1C) is more prevalent. Continuous monitoring of this profile is essential to maintain an accurate understanding of the molecular landscape of the HIV epidemic [...] Read more.

The HIV-1 epidemic in Brazil is predominantly characterized by subtype B, except in the southern states, where subtype C (HIV-1C) is more prevalent. Continuous monitoring of this profile is essential to maintain an accurate understanding of the molecular landscape of the HIV epidemic in Brazil. In this study, we isolated and sequenced seven new HIV-1C strains from the state of Bahia, located in the Northeast region of Brazil. To reconstruct the phylogenetic history of HIV-1C in the Northeast and investigate its connections with other regions of the country and globally, we first compiled a dataset of 3631 HIV-1C sequences from Brazil, Africa, and Europe. As expected, most of the new HIV-1C sequences from Bahia (n = 6) clustered within the well-known Brazilian clade. However, one sequence from Bahia clustered within the African clade, suggesting a possible new introduction of HIV-1C into Brazil. Furthermore, our findings indicate that the HIV-1C cases in Bahia likely originated from southern states, particularly Santa Catarina. This study provides valuable insights into the molecular profile of the HIV epidemic in Brazil, expanding our understanding of HIV-1C beyond the Southern region. Full article

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

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16 pages, 2709 KiB

Open AccessArticle

PD1-Targeted Transgene Delivery to Treg Cells

by Vladislav A. Zhuchkov, Yulia E. Kravchenko, Elena I. Frolova and Stepan P. Chumakov

Viruses 2024, 16(12), 1940; https://doi.org/10.3390/v16121940 - 19 Dec 2024

Viewed by 734

Abstract

Achieving the precise targeting of lentiviral vectors (LVs) to specific cell populations is crucial for effective gene therapy, particularly in cancer treatment where the modulation of the tumor microenvironment can enhance anti-tumor immunity. Programmed cell death protein 1 (PD-1) is overexpressed on activated [...] Read more.

Achieving the precise targeting of lentiviral vectors (LVs) to specific cell populations is crucial for effective gene therapy, particularly in cancer treatment where the modulation of the tumor microenvironment can enhance anti-tumor immunity. Programmed cell death protein 1 (PD-1) is overexpressed on activated tumor-infiltrating T lymphocytes, including regulatory T cells that suppress immune responses via FOXP3 expression. We developed PD1-targeted LVs by incorporating the anti-PD1 nanobody nb102c3 into receptor-blinded measles virus H and VSV-G_mut glycoproteins. We assessed the retargeting potential of nb102c3 and evaluated transduction efficiency in activated T lymphocytes. FOXP3 expression was suppressed using shRNA delivered by these LVs. Our results demonstrate that PD1-targeted LVs exerted pronounced tropism towards PD1⁺ cells, enabling the selective transduction of activated T lymphocytes while sparing naive T cells. The suppression of FOXP3 in Tregs reduced their suppressive activity. PD1-targeted glycoprotein H provided greater specificity, whereas the VSV-G_mut, together with the anti-PD1 pseudoreceptor, achieved higher viral titers but was less selective. Our study demonstrates that PD1-targeted LVs may offer a novel strategy to modulate immune responses within the tumor microenvironment with the potential for developing new therapeutic strategies aimed at enhancing anti-tumor immunity. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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2 pages, 143 KiB

Open AccessEditorial

Exploring the Mechanisms for Virus Invasion at the Barrier of Host Defense Involving Signaling Pathways

by Bumsuk Hahm

Viruses 2024, 16(12), 1939; https://doi.org/10.3390/v16121939 - 19 Dec 2024

Viewed by 469

Abstract

Pathogenic viruses trigger or disrupt multiple signaling networks to establish an environment optimized for their own replication and productive infection [...] Full article

(This article belongs to the Special Issue Viral Strategies to Regulate Host Immunity or Signal Pathways)

34 pages, 2227 KiB

Open AccessReview

Metformin in Antiviral Therapy: Evidence and Perspectives

by Iryna Halabitska, Pavlo Petakh, Oleh Lushchak, Iryna Kamyshna, Valentyn Oksenych and Oleksandr Kamyshnyi

Viruses 2024, 16(12), 1938; https://doi.org/10.3390/v16121938 - 18 Dec 2024

Viewed by 1087

Abstract

Metformin, a widely used antidiabetic medication, has emerged as a promising broad-spectrum antiviral agent due to its ability to modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes cellular energy reserves that viruses rely on, effectively limiting the replication of [...] Read more.

Metformin, a widely used antidiabetic medication, has emerged as a promising broad-spectrum antiviral agent due to its ability to modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes cellular energy reserves that viruses rely on, effectively limiting the replication of pathogens such as influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting the mTOR pathway, crucial for viral protein synthesis and reactivation, is particularly significant in managing infections caused by HIV, CMV, and EBV. Furthermore, metformin reduces oxidative stress and reactive oxygen species (ROS), which are critical for replicating arboviruses such as Zika and dengue. The drug also regulates immune responses, cellular differentiation, and inflammation, disrupting the life cycle of HPV and potentially other viruses. These diverse mechanisms suppress viral replication, enhance immune system functionality, and contribute to better clinical outcomes. This multifaceted approach highlights metformin’s potential as an adjunctive therapy in treating a wide range of viral infections. Full article

(This article belongs to the Special Issue Broad-Spectrum Antivirals and Interaction with Viruses: 2nd Edition)

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Viruses, Volume 16, Issue 12 (December 2024) – 164 articles

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