Virus research最新文献

Bovine leukemia virus (BLV), a member of the delta retrovirus family, is transmitted horizontally among cows. BLV causes enzootic bovine leukosis and has great economic impact on the cattle industry. Recently, secretory-defective Env proteins (e.g., Refrex-1 and FeLIX) have been detected in domestic cats and shown to possess antiretroviral activity against gammaretroviruses via viral receptor interference. Therefore, we investigated whether BLV-derived molecules engineered similarly exhibit antiviral activity against BLV infection. We generated several proteins consisting of the BLV envelope surface unit (SU) region and signal peptide, without the transmembrane region, and tested their inhibitory effects on BLV infection. These artificial mutant Env-SU proteins were detected as secreted proteins in cultured cells. Colony formation and quantitative PCR assays revealed that the secreted Env-SU proteins exhibited an inhibitory effect on BLV infection. In conclusion, the engineered BLV Env-SU protein was found to effectively inhibit BLV infection, likely through a mechanism consistent with viral receptor interference and is expected to contribute to the development of infection-prevention methods against BLV.

Despite the clinical possibility of reducing hepatitis B virus (HBV) to almost undetectable levels through nucleotide analogs or interferon, the process of hepatic fibrosis in HBV hepatitis carriers perdures. This study will investigate the function of RAB25 in HBV-induced liver fibrosis and related mechanisms. In the study, the expression level of RAB25 was shown to be increased within liver fibrotic tissue samples in Gene Expression Omnibus (GEO) microarrays (GSE171294 and GSE84044) and clinical samples as well as in HBV-induced hepatic stellate cells (HSCs) activation. Silencing RAB25 inhibited HSCs activation induced by TGF-β1 and HBV-associated hepatocellular carcinoma cells HepG2.2.15, also significantly inhibited HSCs viability, proliferation, and migration and the expression levels of α-SMA, Collagen I, MMP2, and PCNA. However, the overexpression of RAB25 significantly promoted HBV-associated hepatocellular carcinoma cells and TGF-β1-induced HSCs activation. Mechanistically, silencing RAB25 in HSCs significantly repressed PI3K/AKT activation triggered by HBV-associated hepatocellular carcinoma cells. However, the overexpression of RAB25 notably promoted PI3K/AKT activation. In conclusion, silencing of RAB25 inhibits HBV-associated hepatocellular carcinoma cell-induced hepatic fibrosis by suppressing the PI3K/AKT signaling. RAB25 has been proven to be an underlying target for clinical treatment of HBV-associated liver fibrosis.

Background: Influenza vaccination is an effective measure for reducing the risk of severe influenza infection. However, the task of achieving adequate vaccination rates remains a global challenge. It is unclear whether delayed influenza vaccination is useful for influenza patients. We conducted this study to investigate whether delayed vaccination can reduce mortality in these patients.

Methods: This retrospective cohort study was conducted by reference to the Medical Information Mart for Intensive Care IV (MIMIC-IV) 3.0 database, focusing on patients admitted to the ICU with a diagnosis of influenza. Patients were divided into two groups on the basis of post-admission vaccine use. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to reduce baseline imbalance. The primary outcome was 28-day mortality. Regression analysis and machine learning models, including the Boruta algorithm and LASSO analysis, were used to assess the association between postadmission influenza vaccination use and prognosis results. Sensitivity and subgroup analyses were conducted to evaluate the robustness of the findings.

Results: This study focused on a cohort of 277 influenza patients from 2008 to 2022. Following the implementation of a 1:1 nearest-neighbor PSM procedure, 164 patients were successfully matched. In the PSM cohort, delayed vaccination was not associated with 28-day mortality (Model I: RR, 1.07; 95 % CI, 0.55-2.08; P=0.838; Model II: RR, 0.84; 95 % CI, 0.44-1.61; P = 0.602; Model III: RR, 0.81; 95 % CI, 0.43-1.56; P = 0.534). In the IPTW cohort, the association remained non-significant (Model I: RR, 1.22; 95 % CI, 0.73-2.03; P=0.446; Model II: RR, 1.12; 95 % CI, 0.66-1.91; P=0.662; Model III: RR, 1.17; 95 % CI, 0.72-1.88; P = 0.524). The secondary outcomes, including 60-day mortality, 90-day mortality, ICU mortality and hospital mortality, use of continuous renal replacement therapy and need for mechanical ventilation, remained consistent.

Conclusions: Our study revealed that delayed vaccination did not improve outcomes for critically ill influenza patients, thus highlighting the urgent need for early vaccination to reduce the severity of the disease and protect vulnerable people.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high mortality and limited therapeutic options. Poly(rC)-binding protein 2 (PCBP2) is a multifunctional RNA-binding protein involved in post-transcriptional regulation and innate immune modulation. Although PCBP2 has been reported to negatively regulate antiviral signaling in other viral infections, its role in Dabie bandavirus (DBV) infection remains unclear.

Methods: Single-cell transcriptomic analysis was performed to characterize PCBP2 mRNA expression across immune cell populations in peripheral blood. PCBP2 expression levels were further examined in DBV-infected clinical samples, IFNAR⁻/⁻ mouse models, and THP-1 cells using quantitative RT-PCR, western blotting, and immunohistochemistry. THP-1 cells with plasmid-mediated PCBP2 overexpression or lentivirus-mediated PCBP2 knockdown were established to investigate the functional role of PCBP2. Activation of the RIG-I-like receptor (RLR) signaling pathway was evaluated by assessing key signaling molecules and downstream interferon responses. The impact of PCBP2 on DBV replication was determined by TCID₅₀ assay, viral nucleoprotein (NP) expression, and immunofluorescence analysis.

Results: PCBP2 expression was significantly downregulated during DBV infection in clinical samples, animal models, and cell cultures, and reduced PCBP2 expression was associated with increased disease severity and unfavorable clinical outcomes. Functional analyses demonstrated that PCBP2 suppressed DBV-induced activation of type I interferon signaling and interferon-stimulated genes, including ISG12a and G1P3. Mechanistically, PCBP2 directly interacted with the mitochondrial antiviral signaling protein MAVS and promoted its K48-linked polyubiquitination, resulting in proteasome-dependent degradation and attenuation of the MAVS-TBK1-IRF3 signaling axis. Consistent with its immunosuppressive role, PCBP2 knockdown significantly reduced DBV replication, whereas PCBP2 overexpression enhanced viral replication in THP-1 cells.

Conclusions: These findings identify PCBP2 as a critical negative regulator of RLR-mediated antiviral signaling during DBV infection. By facilitating MAVS degradation and suppressing innate immune responses, PCBP2 promotes viral replication, providing new insights into DBV immune evasion mechanisms and highlighting PCBP2 as a potential host-directed therapeutic target for SFTS.

Several geminiviruses have been show to possess cross-kingdom gene expression capability. In addition, the intergenic region (IR) of geminivirus genomes is known to regulate the transcription of viral early genes (complementary-sense, C-sense) and late genes (virion-sense, V-sense) located in opposite directions in viral genomic DNAs. However, the underlying mechanism remained elusive. In this study, the transcriptional regulation activities in the IR of ageratum yellow vein virus isolate NT (AYVV-NT), a monopartite geminivirus, were characterized in Escherichia coli, by using a promoter-trapping system. A functional bidirectional promoter core and regulatory elements for C- and V-sense genes were identified in the IR of AYVV-NT. Quantitative analyses revealed differences in promoter activity in various E. coli strains, suggesting that promoter regulation is strain-dependent and influenced by bacterial transcription factors. These findings provide insights into how plant-infecting geminiviruses may regulate gene expression in prokaryotic environments and highlight the potential applications of such viral regulatory elements in bacterial expression systems.

Oncolytic viruses (OVs) represent a promising immunotherapy for cancer treatment, though their clinical application is often limited by systemic toxicity and low immunogenicity. To address this, we developed NDV-GT, a genetically engineered Newcastle disease virus that encodes porcine α-1,3-galactosyltransferase. These epitopes are recognized by pre-existing natural antibodies, triggering a hyperacute rejection response characterized by complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Furthermore, NDV-GT modulates the tumor microenvironment by promoting T-cell infiltration and cytokine secretion, converting immunologically "cold" tumors into "hot" ones. Mechanistically, the virus inhibits PI3K/AKT and NF-κB signaling pathways, inducing apoptosis and suppressing tumor proliferation. In a preliminary clinical study of 20 patients with advanced refractory carcinomas, NDV-GT achieved a 90.0% disease control rate with no serious adverse events, underscoring its potential as a novel, safe, and effective oncolytic agent that elicits robust antitumor immunity.