Hendra virus (HeV) is a highly pathogenic paramyxovirus (genus Henipavirus) resident in fruit bats. Spill-over events have resulted in severe disease with high mortality in humans and horses (1). The ability of henipaviruses to evade the interferon (IFN)-mediated antiviral innate immune response is considered to be a critical pathogenesis factor, and is mediated principally by the P, V, W and C proteins through various mechanisms (2). HeV comprises at least 2 genotypes (HeV-g1 and the recently defined HeV-g2) (3). Amongst the viral proteins, P, V and W show the greatest sequence divergence, suggestive of potential functional differences. However, analysis of such differences, which may have significant impact on viral infection and disease, is lacking.
Here, we examined the capacity of P, V and W to antagonize IFN induction and signalling pathways critical to innate immune responses, and associated subcellular trafficking of P/V/W. Using protein expression and viral infection assays, we found that the capacity to antagonize immune signalling is broadly conserved, but significant differences in the extent of antagonism of IFN production differs. Intriguingly, this correlated with differing capacity for nucleocytoplasmic trafficking. Furthermore, viral replication kinetics also appear to differ. Together these data suggest that pathogenesis may differ between the genotypes.
These data provide the first indications that sequence differences in the P gene of genotypes of a henipavirus result in altered function, including in immune evasion/replication. Ongoing research is addressing the potential relationship of these functional differences, which is important to understanding risks associated with outbreaks of different genotypes.