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An asymptomatic and persistent enteric virus is restricted from causing disease by the host immune system in a STAT1-dependent manner

University of British Columbia

Mammalian evolution has occurred while hosting mutualistic, commensal, and pathogenic micro- and macro-organisms for millennia. The virome can provide beneficial immune-stimulating signals or it can provide detrimental immune-stimulating signals that impact host health. Mechanisms that are important for relaying signals from the virome to the immune system are not well understood. Here I investigate the importance of a signalling molecule, Signal Transducer and Activator of Transcription-1 (STAT1), in controlling the immune response to an asymptomatic and persistent virus infection by murine Norovirus strain CR6 (CR6). By evaluating clinical parameters and virus-specific adaptive immune responses I was able to better understand how the host can coordinate appropriate immune responses to persistent enteric virus infections. Moreover, I confirmed that host-virome signals could limit CR6 burdens and systemic dissemination in immunosufficient mice. I conclude with a new perspective of how CR6 persists asymptomatically; by therapeutically limiting CR6 replication, I uncovered that unlike other persistent virus infections CR6 persistence may not be due to the apparent weak immune responses against it. Importantly, CR6 persistence requires STAT1 signalling, because deficient signalling leads to uncontrolled virus replication and ultimately host mortality, which limits virus transmission potential

Text

2017-10-27

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/63463

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/