| Autor: |
Deffrasnes C; Department of Microbiology, Biomedicine Discovery Institute, Monash University, 19 Innovation Walk (Bldg 76), Melbourne, VIC 3800, Australia., Luo MX; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Road, The University of Melbourne, Melbourne, VIC 3010, Australia., Wiltzer-Bach L; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, 19 Innovation Walk (Bldg 77), Melbourne, VIC 3800, Australia., David CT; Department of Microbiology, Biomedicine Discovery Institute, Monash University, 19 Innovation Walk (Bldg 76), Melbourne, VIC 3800, Australia., Lieu KG; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Road, The University of Melbourne, Melbourne, VIC 3010, Australia., Wang LF; Programme in Emerging Infectious Disease, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.; SingHealth Duke-NUS Global Health Institute, 8 College Road, Singapore 169857, Singapore., Jans DA; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, 19 Innovation Walk (Bldg 77), Melbourne, VIC 3800, Australia., Marsh GA; Australian Centre for Disease Preparedness, CSIRO Health and Biosecurity, 5 Portarlington Road, East Geelong, VIC 3220, Australia., Moseley GW; Department of Microbiology, Biomedicine Discovery Institute, Monash University, 19 Innovation Walk (Bldg 76), Melbourne, VIC 3800, Australia. |
| Abstrakt: |
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 phosphoprotein (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 to compare proteins of viruses adapted to divergent bat species. We report that key functions of P protein in the antagonism of interferon/signal transducers and activators of transcription 1 (STAT1) signaling 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. |
