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.

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.

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.

We computationally characterized G-quadruplex (G4) distributions across 31 coronavirus genomes to identify conserved structural features as potential antiviral therapeutic targets. Through an integrated approach combining consensus G4 detection, dinucleotide-preserving null models, and pooled Poisson rate ratios, we identified a paradoxical G4 distribution pattern: genome-wide depletion (mean fold change = 0.56) coupled with strong regional enrichment in Spike (S) protein (incidence rate ratio [IRR] = 17.9; 95% CI: 11.7-27.6) and Nucleocapsid (N) protein (IRR = 15.2; 95% CI: 8.7-26.6), while untranslated regions (UTRs) showed complete G4 absence. Thermodynamic stability assessment identified 38 stable G4 candidates (ΔG < -5 kcal/mol), with 52.6% concentrated in Nucleocapsid protein regions, suggesting candidates for structure-based antiviral drug development awaiting experimental confirmation. This paradoxical distribution pattern-genome-wide depletion coupled with strong regional enrichment in functionally critical proteins (Spike and Nucleocapsid)-provides a mechanistic framework for developing betacoronavirus-targeted therapeutics based on conserved G4 structures.

The host-hepatitis C virus (HCV) interaction determines whether the acute phase of HCV infection will undergo complete resolution or progress to the development of viral persistence and, ultimately, chronic HCV infection. The host cell mechanism that fights against the virus culminates in the production of interferons (IFNs), IFN-stimulated genes, and cytokines as well as the induction of autophagy and apoptosis. Innate immune responses modulate adaptive immune responses. T cells often fail and the virus persists as a result of T-cell exhaustion and the emergence of viral escape mutations. Exhausted T cells are unable to control the virus infection. A reversal of T-cell exhaustion after treatment with direct-acting antivirals (DAAs), characterized by the enhanced proliferation of HCV-specific CD8+T cells, down-regulates programmed cell death-1 (PD-1) expression and transitions cells towards a TCF-1+CD127+ memory-like T-cell phenotype. The early initiation of treatment with DAAs during the acute phase of HCV infection is important because it reduces immune exhaustion and results in stronger HCV-specific T-cell responses after treatment, thereby reducing the risk of possible reinfection. Furthermore, since the successful treatment of HCV by DAAs does not lead to the complete reversal of T-cell exhaustion, HCV reinfections may occur. Therefore, a prophylactic vaccine is needed to avoid reinfections and achieve the global elimination of HCV infections. This review provides an overview of the current understanding of the pathophysiology behind HCV infection where the current research and treatment are pointing towards.