Hendra virus genotypes 1 and 2 differ in V protein-mediated immune evasion

Hendra virus (HeV) is a highly pathogenic virus endemic to Australia that causes lethal infections in horses and humans following spillover from bat reservoirs. There are two known genotypes: genotype 1 and 2 (HeV-g1 and HeV-g2). Both have caused lethal disease in horses, but HeV-g1 causes a more severe disease than HeV-g2 in non-human primates. The molecular mechanisms underlying these differences are poorly understood. The capacity of viruses to evade the interferon (IFN)-mediated antiviral innate immune response is important in infection and disease, and in HeV, the virulence factor V protein is a key mediator and one of the most divergent proteins between the genotypes. We compared the IFN antagonist functions of the V proteins of HeV-g1 and HeV-g2, finding that HeV-g1-V was more potent than HeV-g2-V in antagonizing the induction of type-I IFN; we further found that the proteins differ in nucleocytoplasmic localization. Consistent with these findings, HeV-g1 suppressed type-I IFN production more effectively than HeV-g2 during infection. These data reveal differences in the fundamental biology of HeV genotypes, which may be significant to pathogenesis.