Viruses-Basel最新文献

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

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

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

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

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

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

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

The emergence and spread of highly pathogenic avian influenza virus A subtype H5N1 (HP H5N1-IAV), particularly clade H5N1 2.3.4.4b, pose a severe global health threat, affecting various species, including mammals. Historically, cattle have been considered less susceptible to IAV, but recent outbreaks of H5N1-IAV 2.3.4.4b in dairy farms suggest a shift in host tropism, underscoring the urgency of expanded surveillance and the need for adaptable diagnostic tools in outbreak management. This study investigated the presence of anti-nucleoprotein (NP) antibodies in serum and milk and viral RNA in milk on dairy farms affected by outbreaks in Texas, Kansas, and Michigan using a multi-species IAV ELISA and RT-qPCR. The analysis of ELISA results from a Michigan dairy farm outbreak demonstrated a positive correlation between paired serum and milk sample results, confirming the reliability of both specimen types. Our findings also revealed high diagnostic performance during the convalescent phase (up to 96%), further improving sensitivity through serial sampling. Additionally, the evaluation of diagnostic specificity using serum and milk samples from IAV-free farms showed an excellent performance (99.6%). This study underscores the efficacy of the IAV NP-blocking ELISA for detecting and monitoring H5N1-IAV 2.3.4.4b circulation in dairy farms, whose recent emergence raises significant animal welfare and zoonotic concerns, necessitating expanded surveillance efforts.

Hepatitis E virus (HEV) poses a significant global health threat, with an estimated 20 million infections occurring annually. Despite being a self-limiting illness, in most cases, HEV infection can lead to severe outcomes, particularly in pregnant women and individuals with pre-existing liver disease. In the absence of specific antiviral treatments, the exploration of RNAi interference (RNAi) as a targeted strategy provides valuable insights for urgently needed therapeutic interventions against Hepatitis E. We designed small interfering RNAs (siRNAs) against HEV, which target the helicase domain and the open reading frame 3 (ORF3). These target regions will reduce the risk of viral escape through mutations, as they belong to the most conserved regions in the HEV genome. The siRNAs targeting the ORF3 efficiently inhibited viral replication in A549 cells after HEV infection. Importantly, the siRNA was also highly effective at inhibiting HEV in the persistently infected A549 cell line, which provides a suitable model for chronic infection in patients. Furthermore, we showed that a 5' triphosphate modification on the siRNA sense strand activates the RIG-I receptor, a cytoplasmic pattern recognition receptor that recognizes viral RNA. Upon activation, RIG-I triggers a signaling cascade, effectively suppressing HEV replication. This dual-action strategy, combining the activation of the adaptive immune response and the inherent RNAi pathway, inhibits HEV replication successfully and may lead to the development of new therapies.

The porcine reproductive and respiratory syndrome virus (PRRSV) belongs to the Arteriviridae family and is a single-stranded, positively stranded RNA virus. The currently available PRRSV vaccines are mainly inactivated and attenuated vaccines, yet none of the commercial vaccines can provide comprehensive, long-lasting, and effective protection against PRRSV. SR717 is a pyridazine-3-carboxamide compound, which is commonly used as a non-nucleoside STING agonist with antitumor and antiviral activities. Nevertheless, there is no evidence that SR717 has any antiviral effects against PRRSV. In this study, a dose-dependent inhibitory effect of SR717 was observed against numerous strains of PRRSV using qRT-PCR, IFA, and WB methods. Furthermore, SR717 was found to stimulate the production of anti-viral molecules and trigger the activation of the signaling cascade known as the stimulator of interferon genes (STING) pathway, which contributed to hindering the reproduction of viruses by a certain margin. Collectively, these results indicate that SR717 is capable of inhibiting PRRSV infection in vitro and may have potential as an antiviral drug against PRRSV.