Preprint Brief Report Version 1 Preserved in Portico This version is not peer-reviewed

Phenotypic Divergence of P Proteins of Australian Bat Lyssavirus Lineages Circulating in Microbats and Flying Foxes

Version 1 : Received: 18 February 2021 / Approved: 19 February 2021 / Online: 19 February 2021 (10:06:42 CET)

A peer-reviewed article of this Preprint also exists.

Deffrasnes, C.; Luo, M.-X.; Wiltzer-Bach, L.; David, C.T.; Lieu, K.G.; Wang, L.-F.; Jans, D.A.; Marsh, G.A.; Moseley, G.W. Phenotypic Divergence of P Proteins of Australian Bat Lyssavirus Lineages Circulating in Microbats and Flying Foxes. Viruses 2021, 13, 831. Deffrasnes, C.; Luo, M.-X.; Wiltzer-Bach, L.; David, C.T.; Lieu, K.G.; Wang, L.-F.; Jans, D.A.; Marsh, G.A.; Moseley, G.W. Phenotypic Divergence of P Proteins of Australian Bat Lyssavirus Lineages Circulating in Microbats and Flying Foxes. Viruses 2021, 13, 831.

Journal reference: Viruses 2021, 13, 831
DOI: 10.3390/v13050831

Abstract

Bats are reservoirs of many pathogenic viruses including the lyssaviruses rabies virus (RABV) and Australian bat lyssavirus (ABLV). Lyssavirus strains are closely associated with particular host reservoir species, with evidence of specific adaptation. Associated phenotypic changes remain poorly understood but are likely to involve P protein, a key mediator of the intracellular virus-host interface. Here, we examine the phenotype of P protein of ABLV, which circulates as two defined lineages associated with frugivorous and insectivorous bats, providing the opportunity compare proteins of viruses adapted to divergent bat species. We report that key functions of P protein in interferon/STAT1 antagonism and the capacity of P protein to undergo nuclear trafficking differ between lineages. Molecular mapping indicates that these differences are functionally distinct, and appear to involve modulatory effects on regulatory regions or structural impact, rather than changes to defined interaction sequences. This results in partial but significant phenotypic divergence, consistent with ‘fine-tuning’ to host biology, and with potentially distinct properties in the virus-host interface between bat families that represent key zoonotic reservoirs.

Subject Areas

Australian bat lyssavirus; lyssavirus; rabies virus; immune evasion; nuclear trafficking; interferon; STAT1; bats; virus reservoirs; adaptation

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