Boyi Xu, Chenchen Jiang, Lei Di, Lan Zhou, Zhouyuan Wang, Yi Tang, Rendong Fang, Hongzhi Wang
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Novel Duck Orthoreovirus σA Protein Inhibits Interferon Signaling by Impeding STAT1/STAT2 Nuclear Translocation
Novel duck orthoreovirus (NDRV) infection induces severe splenic necrosis and immunosuppression in ducks, leading to substantial economic losses in the duck farming industry. While the avian orthoreovirus (ARV) σA protein is known to exhibit interferon (IFN) antagonistic activity, whether NDRV possesses a similar function and the underlying molecular mechanisms remain unclear. This study demonstrates that NDRV not only counteracts the antiviral clearance effect of type I IFN (IFN-I) but also markedly suppresses IFN-mediated signal transduction. Further investigations revealed that the NDRV σA protein specifically inhibits IFN signaling and its associated antiviral effects by blocking the nuclear translocation of STAT1/STAT2, thereby, facilitating innate immune escape. This discovery elucidates for the first time a novel mechanism by which the NDRV σA protein regulates the JAK-STAT signaling pathway. These findings provide a theoretical foundation for the development of antiviral strategies targeting immune regulation.
期刊介绍:
Transboundary and Emerging Diseases brings together in one place the latest research on infectious diseases considered to hold the greatest economic threat to animals and humans worldwide. The journal provides a venue for global research on their diagnosis, prevention and management, and for papers on public health, pathogenesis, epidemiology, statistical modeling, diagnostics, biosecurity issues, genomics, vaccine development and rapid communication of new outbreaks. Papers should include timely research approaches using state-of-the-art technologies. The editors encourage papers adopting a science-based approach on socio-economic and environmental factors influencing the management of the bio-security threat posed by these diseases, including risk analysis and disease spread modeling. Preference will be given to communications focusing on novel science-based approaches to controlling transboundary and emerging diseases. The following topics are generally considered out-of-scope, but decisions are made on a case-by-case basis (for example, studies on cryptic wildlife populations, and those on potential species extinctions):
Pathogen discovery: a common pathogen newly recognised in a specific country, or a new pathogen or genetic sequence for which there is little context about — or insights regarding — its emergence or spread.
Prevalence estimation surveys and risk factor studies based on survey (rather than longitudinal) methodology, except when such studies are unique. Surveys of knowledge, attitudes and practices are within scope.
Diagnostic test development if not accompanied by robust sensitivity and specificity estimation from field studies.
Studies focused only on laboratory methods in which relevance to disease emergence and spread is not obvious or can not be inferred (“pure research” type studies).
Narrative literature reviews which do not generate new knowledge. Systematic and scoping reviews, and meta-analyses are within scope.