Virus Genes最新文献

One challenge in utilizing the Measles virus (MV) for cancer therapy is the number of virus particles required, nearly a million times greater than the amount reported for vaccination. This study aims to design and develop a cell line with increased production capacity to supply the required amounts of MV in oncolytic virotherapy. The sphingosine kinase 1 (SphK1) gene was inserted into a pIRES2-EGFP plasmid and transiently transfected into four cell lines: MRC-5, HEK293, Vero, and A549. Fluorescent light intensity was measured using flow cytometry, and the MV production titer was determined using the TCID50 method. Transient transfection of pIRES2-EGFP-SphK1 was associated with increases in MV yield of approximately 3 logs in HEK293, 2 logs in Vero and A549, and 1 log in MRC-5 cells compared to controls and has impacted the morphology of MRC-5 cells. The top 100 genes co-expressed with SphK1 were identified with the ARCHS4 RNA-seq data resource, and functional enrichment with EnrichR suggested involvement in interleukin and cytokine signaling, extracellular matrix organization, and stress responses. The observed results indicate that augmenting the expression of the SphK1 gene may enhance MV production and influence cellular behavior, although effects appear to be cell line-dependent. A better understanding of cell-specific S1P signaling and cytoskeletal regulation could assist in optimizing cell lines for scalable virotherapy production.

Human retroviruses such as HIV-1 and HTLV-1 hijack host cellular mechanisms for their replication, survival, and pathogenesis, often causing profound genomic instability. This review explores the dual role of homologous recombination (HR), explicitly mediated by the recombinase RAD51, in the context of retroviral infections. RAD51 is central to high-fidelity repair of DNA double-strand breaks, yet its activity is manipulated differently by HIV-1 and HTLV-1. In HIV-1 infection, RAD51 expression is elevated by viral proteins like Tat and Vpr, promoting DNA repair and enhancing viral transcription through interactions with NF-κB, thereby supporting viral persistence. Conversely, HTLV-1 suppresses RAD51-mediated HR via viral proteins such as p30 and Tax, promoting error-prone DNA repair pathways that contribute to oncogenesis. These contrasting effects may underscore RAD51's functional plasticity as both a facilitator of viral replication and a potential antiviral restriction factor. Furthermore, the therapeutic modulation of RAD51 activity-especially in combination with PARP inhibitors offers promising avenues for treating retrovirus-associated malignancies such as adult T-cell leukemia/lymphoma. This review highlights RAD51 as a pivotal connection in the interplay between genome stability and retroviral pathobiology.

Bluetongue (BT), a significant economic disease affecting domestic and wild ruminants, requires rapid and precise diagnostic methods. The diversity of BTV serotypes, coupled with their high genetic and antigenic variability, poses substantial challenges for disease control and prevention. To address this, multiplex Magpix assays were developed for the simultaneous and accurate detection of BTV serotypes and topotypes. Primers and probes were designed to target segment 2 (Seg-2) of the BTV genome, a highly variable region that enables serotype-specific identification using probes conjugated to magnetic beads.The developed Magpix assays facilitate the identification of multiple BTV serotypes from a single sample. Five multiplex Magpix assays were created to detect eastern and western strains of 12 distinct currently circulating BTV serotypes (1, 2, 3, 4, 5, 9, 10, 12, 16, 21, 23, and 24) in India to align with the current epidemiological landscape. These assays were categorized as follows: eastern assays-E1 (1e, 2e, 4e), E2 (3e, 9e), and E3 (16e, 21e, 23e); and western assays-W1 (1w, 10w, 12w) and W2 (2w, 5w, and 24w). The detection limits varied across assays, with E1 showing a higher detection limit (500 pg) compared to E2 (50 pg), E3 (50 pg), W1 (5 pg), and W2 (5 pg). Importantly, the assays exhibited no cross-reactivity with other related viruses.These five multiplex Magpix assays provide an effective diagnostic tool for identifying circulating BTV strains in India. Additionally, the system offers flexibility for expansion to include more serotypes as needed, enhancing its utility for BT surveillance and control. In summary, the introduction of these advanced diagnostic methods presents a significant opportunity for more strategic and effective management of BTV, thereby ensuring better protection for both livestock and the livelihoods dependent on them.

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.