Virus Genes最新文献

We studied the fate of a gene called ORF8 in different coronaviruses species during their passage to humans. We showed that this gene harbored stop codons in many epidemic SARS-CoV-2 variants in humans and in up to 86% of SARS-CoV-2 circulating in 2023 and therefore could be a non-virulence gene whose disappearance helps the epidemics spread. We questioned whether this is a general phenomenon following coronavirus passage to humans from another species, most often bats. We studied SARS-CoV, SARS-CoV-2, MERS-CoV, and the four coronaviruses endemic in humans for several years or decades and observed gene degradation after species jumps from animals to humans. For SARS-CoV-2, we observed the progressive disappearance of its ORF8 with one or several stop codons and partial or even complete deletions, which is reminiscent of the 'Cheshire cat phenomenon' described in the L. Caroll's Alice's Adventures in Wonderland novel, where a cat gradually disappears to leave only a smile. In viruses that emerged earlier in humans and adapted to this host, only footprints of a few bases remain, but which are significantly associated with the original gene.

The H3 avian influenza virus (AIV) is a common avian pathogen, widely prevalent among domestic poultry and wild birds. In China, H3N8 AIVs led to two confirmed cases of human infection in 2022, followed by a deadly case in 2023. In 2019, an H3N8 AIV was identified in chickens monitored within live poultry markets of eastern China. To investigate the genetic connections between these eastern Chinese AIV strains and other influenza viruses, we sequenced all gene segments of these strains and performed a comparative analysis with sequences retrieved from the GenBank database. We performed phylogenetic analysis and molecular characterization of the virus and then assessed the viral growth kinetics and pathogenicity in mice. The results demonstrated that the H3N8 AIV possesses genetic features of H3, H4, H7, and H10 AIVs, which have been identified in ducks and chickens in China. The strain could stably replicate in DF-1, MDCK, and A549 cells. In animal experiments, the strain demonstrated moderate pathogenicity and replicated in mice without prior adaptation. In conclusion, a reassortment occurred between AIVs from diverse avian hosts, and the ongoing dissemination of H3N8 AIVs may pose a threat to human health.

Human parvovirus B19 (B19V) primarily targets erythroid progenitor cells and is associated with various hematological disorders. However, the detailed mechanisms underlying its life cycle, particularly the viral assembly process, remain largely unknown. In this study, we used in vitro engineered DNA-binding molecule-mediated chromatin immunoprecipitation (in vitro enChIP) to identify host proteins associated with the B19V genome in infected UT7/Epo-S1 cells. Using guide RNAs targeting the viral terminal hairpin region, we successfully enriched viral genomic DNA. Mass spectrometry analysis of the precipitated fractions revealed specific enrichment of desmosomal proteins, including desmoplakin (DSP), desmoglein-1, desmocollin-1, and junction plakoglobin, suggesting that the components of the entire desmosome complex may be associated with the B19V genome. Immunofluorescence microscopy showed that the viral VP2 protein was strongly localized to the extranuclear foci, where it colocalized with DSP. Pull-down assays further demonstrated that VP2, but not VP1, interacted with DSP, indicating that the VP1-unique N-terminal region (VP1u) may inhibit this interaction. Notably, B19V-infected cells displayed reduced cell-cell adhesion and diminished cellular aggregation, implying that these interactions may be involved in the disruption of cell adhesion during infection. These findings revealed a novel mechanism by which B19V exploits the host desmosomal machinery to facilitate viral propagation in infected cells.

In Saudi Arabia, where millions from different countries converge on the holy sites of Makkah and Madina, surveillance of respiratory viruses, especially influenza viruses, is of utmost importance. The influenza B virus (IBV) is constantly changing genetically, which affects vaccine effectiveness and immune evasion. While IBV epidemiology has been studied extensively around the world, little is known about its genetic dynamics in Saudi Arabia. The current study aims to investigate the genetic evolution, antigenic diversity, and potential vaccine mismatches of IBV in Riyadh throughout the 2020-2023 epidemic season. IBV-positive samples underwent whole-HA and NA gene sequencing and phylogenetic analysis. The HA and NA genes were examined for mutations, antigenic site amino acid substitutions, and glycosylation patterns. Divergence was assessed using a comparative examination of vaccination strains. During the three study seasons (winters 2020/21, 2021/22, and 2022/23), 5.26% of participants had confirmed IBV profiles, mostly female children aged 5-12 years. The HA gene contains 118 mutations, 46 of which are amino acid substitutions with significant antigenic site changes. In comparison to the B/Austria/1359417/2021 vaccination strain, 50 mutations were found, including a unique 9-nucleotide deletion. Increased O-glycosylation in Riyadh isolates indicates improved immune evasion. The phylogenetic analysis reveals that all Riyadh isolates (n = 20) belong to the B/Victoria lineage. The major lineage, B/Victoria V1A.3a.2, is consistent with worldwide circulation patterns. IBV in Riyadh shows high genetic drift and antigenic diversity, which may limit vaccine effectiveness. Continuous genomic surveillance is critical for detecting new mutations and directing vaccination updates.

Vesicular stomatitis virus (VSV) is a zoonotic infectious disease that severely impacts the livestock economy. Infection causes vesicle formation, epithelial cell lysis, and severe interstitial edema, accompanied by inflammatory cell infiltration. It can also infect humans and result in a 3 to 5-day illness characterized by fever, headache, fatigue, and muscle aches. (Phosphoribosyl pyrophosphate synthetase 2) PRPS2, a core rate-limiting enzyme in purine and pyrimidine nucleotide biosynthesis, is a key regulator of nucleotide metabolism. In this study, we found that knockdown of PRPS2 significantly attenuated VSV-GFP infection efficiency and suppressed viral replication. Conversely, overexpression of PRPS2 promoted VSV-GFP replication. Further mechanistic exploration revealed that PRPS2 knockdown enhanced IRF3 phosphorylation and upregulated the transcription of IFN-β, CXCL10, and ISG56. This study demonstrates that PRPS2 likely regulates the host innate immune response by modulating IRF3 phosphorylation, thereby influencing VSV replication. These findings reveal the role of PRPS2 in host antiviral immunity and deepen the theoretical understanding of VSV-host interactions.

Rabies, a neglected tropical zoonotic disease caused by the rabies virus (RABV), results in fatal encephalitis in both humans and animals. India, a high-burden country, accounts for nearly 30% of global rabies-related deaths. Robust surveillance combined with large-scale genomic sequencing of RABV is essential to monitor viral spread, evolution, and diversity, critical for developing targeted interventions. However, the lack of comprehensive whole genome data on Indian RABV isolates hampers detailed molecular epidemiological analysis. In this study, 630 RABV-positive samples from diverse hosts and regions across India were sequenced using an amplicon-based Illumina workflow. Phylogenetic analysis identified the Arctic-like 1a lineage as predominant, exhibiting high genetic homogeneity. Additionally, Arctic-like 1b and the Indian subcontinent lineages were detected, indicating the presence of co-circulating strains. Geographic clustering observed at the state level suggested localised transmission with limited inter-state viral movement. Mutation and selection pressure analyses revealed conserved amino acid substitutions in the glycoprotein, without alterations in key antigenic sites. These findings underscore the feasibility and significance of large-scale genomic surveillance of RABV in India, pivotal for informing effective rabies control strategies and advancing the global goal of eliminating dog-mediated human rabies deaths by 2030.

Bovine parvovirus 2 (BoPV-2), officially classified as Ungulate copiparvovirus 1 by the ICTV, and Bopivirus A, a recently recognized picornavirus, are poorly characterized viruses sporadically reported in cattle worldwide. Here, we describe the first detection of BoPV-2 and Bopivirus A in Iran-and potentially the Middle East-through RNA-seq analysis of a diarrheic neonatal calf. Four BoPV-2 contigs (82-85% nucleotide identity; 91-100% amino acid identity) were identified, clustering within the Ungulate copiparvovirus 1 clade, while the Bopivirus sequence grouped with Chinese strains BoP8 and BoP9, supporting its classification within lineage A2. Both viruses were confirmed by phylogenetic analyses based on partial RdRp (3Dpol) and ORF regions. The concurrent detection of these viruses in a single calf suggests possible co-circulation in early-life gastrointestinal infections, highlighting the complexity of the calf virome. Notably, RNA detection of the DNA virus BoPV-2 in fecal material indicates potential intestinal replication and shedding, raising questions about its transmission dynamics. These findings expand the geographic range of BoPV-2 and Bopivirus A and underscore the value of metagenomic surveillance for uncovering under-characterized viral agents contributing to neonatal calf diarrhea.

The complete genomic characterization of two Seoul virus (SEOV) strains of Rattus norvegicus captured in Buenos Aires City in 1983 and 2001 is reported for the first time. The nucleotide and amino acid identities observed between the Argentinian SEOV strains for the coding regions of the S, M, and L segments and their deduced amino acid sequences were similar to those observed between Argentinian SEOV strains and those from other parts of the world. Phylogenetic analyses using the maximum-likelihood method show that the two Argentinian SEOV strains grouped with other strains from Asia, Europe, and the US in two different clades, indicating possible independent introductions in Argentina and more studies are needed to understand the evolution and migratory movements of the SEOV. Human cases of disease have not yet been reported in Argentina, and further eco-epidemiological studies are required in order to analyze the pathogenic potential of the SEOV strains circulating in our country.

Genomic surveillance of respiratory viruses is an expanding field. As of 2024, only 110 (near-) complete genomes of human parainfluenza virus type 2 (HPIV2) were available in GenBank, none being from France. Here we aimed to obtain and analyze HPIV2 genomes from residues of HPIV2 RNA-positive respiratory samples from patients diagnosed in university hospitals of Marseille, Southern France, between 2017 and 2022. Prior to next-generation sequencing (NGS), an in-house PCR-based enrichment strategy was implemented with primers chosen with PrimalScheme. NGS used Illumina technology on a NovaSeq 6000 instrument. HPIV2 genomes were generated from NGS reads by mapping and de novo assembly using CLC Genomics. Mutations were identified by NextClade, and phylogeny was performed by MEGA and NextClade. Seventy-seven near-complete (≥ 90% coverage) genomes and 239 genomes with ≥ 70% coverage were recovered from 318 HPIV2 RNA-positive samples. Two major genotypes, G1a (n = 129 genomes) and G3 (110), were identified, and five subgenotypes, namely G1a.5 (n = 23 genomes), G1a.8 (68), G3.4 (4), G3.5 (7), and G3.7 (23), were newly proposed. Genotype-specific mutations were in the L gene (encoding RNA polymerase) for G1a (T14612A/T11981A/T12374C) and the hemagglutinin-neuraminidase-encoding gene for G3 (G8171A/A14057G/10367G). Subgenotype G3 was only detected in 2019. Subgenotype G1a was absent during the 2021-2022 winter, before becoming majority again during autumn 2022. Although preliminary, this work increased by 70% the number of HPIV2 genomes available worldwide and produced the first genomes from France. It shows an evolution of genotypes, with significant genetic diversity, and of their distribution. It justifies the genomic surveillance of this virus.

Hepatitis B virus (HBV) infection remains a leading cause of chronic liver disease and liver failure worldwide. Although miR-148a-3p has been implicated in liver pathophysiology, its specific role in HBV replication through autophagy-related signaling pathways is not fully understood. This study aimed to investigate the effects of miR-148a-3p on HBV transcription and replication, focusing on its regulation of AMPK/mTOR-dependent autophagy. HepG2.2.15 cells were transfected with miR-148a-3p mimics or inhibitors, with or without the AMPK agonist AICAR. HBV replication markers (pgRNA, HBsAg, HBeAg), autophagy-related proteins (LC3, p62, Beclin-1), and AMPK/mTOR/S6 pathway components were analyzed by Western blotting, ELISA, qRT-PCR, and immunofluorescence. Cell viability was measured using the MTT assay at 12-72-h post-transfection. Overexpression of miR-148a-3p increased pgRNA, HBsAg, and HBeAg production (P < 0.01), enhanced autophagy as indicated by elevated Beclin-1 and LC3-II with reduced p62 (P < 0.01), activated AMPK, and inhibited mTOR and S6 phosphorylation (P < 0.01). In contrast, miR-148a-3p knockdown reduced HBV replication and autophagy, effects that were partially reversed by AICAR treatment (P < 0.01). miR-148a-3p promotes HBV transcription and replication by inducing autophagy via AMPK activation and mTOR/S6 suppression. These findings provide mechanistic insight into HBV pathogenesis and identify miR-148a-3p as a potential therapeutic target for regulating HBV replication and autophagy.