The C-terminal nsP1a protein of porcine astrovirus antagonizes interferon beta production by targets MAVS and IRF3 signaling.

Astroviruses (AstV) are positive-sense, single-stranded RNA viruses that can infect humans and a broad spectrum of mammalian and avian species. Recently, Astrovirus strains from various hosts have been implicated in extra-intestinal infections, leading to symptoms such as encephalitis, meningitis, hepatitis, nephropathy and gout. These findings highlight the significant risks associated with its pathogenicity and its potential for interspecies transmission. The astrovirus nsP1a polyprotein is known to produce at least four distinct products. However, the precise demarcation of boundaries for these proteins remains unclear yet. Interferons, along with their antiviral immune responses, have important roles during early stages of viral infection. Viruses typically employ their encoded proteins to evade host-generated immune responses during infections through different mechanisms. In this study, we identified nonstructural proteins of PAstV1 that hinder the type I interferon (IFN) pathway. This was achieved using an IFN-β promoter reporter and by analyzing IFN-β mRNA levels in HEK 293 T cells. Our findings indicate that PAstV1 nsP1a/4 inhibits IFN-β promoter activation mediated via components in the RIG-I-like receptor (RLR) signaling pathway, specifically RIG-I, MDA5, MAVS, and IRF3. Further analyses revealed that PAstV1 nsP1a/4 protein interacts with MAVS and IRF3 to impede the RIG-I/MDA5 signaling and affects their ability to induce IFN. Overall, our results demonstrate that the ectopic expression of PAstV1 nsP1a/4 antagonizes IFN-β production by interacts with MAVS and IRF3. This reveals a novel mechanism by which PAstV nonstructural proteins evade the host's innate antiviral immune response.