Poster Presentation Lorne Infection and Immunity 2023

Divergence in immune evasion capacity between different genotypes of Hendra and Nipah virus (#204)

Melanie Tripp 1 2 , Cassandra David 2 , Jasmina Luczo 1 , Kim Halpin 1 , Gregory Moseley 2
  1. AAHL, CSIRO-ACDP, East Geelong, VIC, Australia
  2. Department of Microbiology, Monash University, Clayton, VIC, Australia

Hendra (HeV) and Nipah virus (NiV) are highly pathogenic paramyxoviruses that, with several related viruses, form the genus Henipavirus. The natural reservoir of HeV and NiV is fruit bats, and ongoing spillover events have resulted in severe disease with high mortality in humans, horses, and pigs (1). The ability of these viruses to evade the interferon (IFN)-mediated innate immune response is considered to be a critical pathogenesis factor, and is mediated principally by accessory proteins encoded by the P gene; P, V, W and C through a variety of mechanisms (2). HeV and NiV both comprise at least 2 genotypes (HeV-g1 and the recently defined HeV-g2, in addition to NiV Bangladesh [NiV B] and Malaysia [NiV M]) (3). Differences in outcomes of spillover of NiV B and NiV M suggest potential variation in molecular mechanisms of pathogenesis; however data relating to this is currently lacking (4). While most of the viral proteins have high amino acid homology, P, V and W show the greatest divergence.

 

Here, we examined potential differences between P, V and W of different genotypes in antagonism of the critical IFN induction and signaling pathways. Using approaches including fluorescence microscopy, reporter assays, and immunoprecipitation analysis, we found that the capacity to inhibit IFN pathways is broadly conserved. However, significant differences in the extent of antagonist function were identified between viral species and genotypes. Ongoing research will define the molecular basis of these differences and their significance in infection, using our established approaches and unique biosafety facilities (5, 6).

 

These data provide the first indications that substitutions between the P gene of henipavirus genotypes have impacted functions in IFN-antagonism. This provides insights into potential differences in disease outcomes and is important to understanding the risks associated with outbreaks of different viruses and genotypes.

  1. Halpin K, Rota P. A Review of Hendra Virus and Nipah Virus Infections in Man and Other Animals. Zoonoses - Infections Affecting Humans and Animals. 2014:997–1012.
  2. Audsley MD, Moseley GW. Paramyxovirus evasion of innate immunity: Diverse strategies for common targets. World J Virol. 2013;2(2):57-70
  3. Wang J, Anderson DE, Halpin K, Hong X, Chen H, Walker S, et al. A new Hendra virus genotype found in Australian flying foxes. Virol J. 2021;18(1):197.
  4. Mire CE, Satterfield BA, Geisbert JB, Agans KN, Borisevich V, Yan L, et al. Pathogenic Differences between Nipah Virus Bangladesh and Malaysia Strains in Primates: Implications for Antibody Therapy. Sci Rep. 2016;6:30916
  5. Brice AM, Rozario AM, Rawlinson SM, David CT, Wiltzer-Bach L, Jans DA, et al. Lyssavirus P Protein Isoforms Diverge Significantly in Subcellular Interactions Underlying Mechanisms of Interferon Antagonism. J Virol. 2022:e0139622.
  6. Chen M, Tachedjian M, Marsh GA, Cui J, Wang LF. Distinct Cell Transcriptomic Landscapes Upon Henipavirus Infections. Front Microbiol. 2020;11:986.