FUNCTION AND EVOLUTION OF HOST ANTIVIRAL FACTORS
Semih U. Tareen1,2
1 Molecular and Cellular Biology Program, University of Washington, Seattle, WA,
USA, 2 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle,
WA, USA. Hosts have to be able to counteract pathogenic diversity with a broad palette of host
immunity. In addition to innate and adaptive immunity, �intrinsic immunity� is a third
type of host immunity in vertebrates. Intrinsic immunity consists of cell autonomous
intracellular factors that protect the genome against retroviruses and retrotransposons.
Unlike adaptive immunity, similar to innate immunity, intrinsic immunity does not need
to go through activation or immunological education. An example intrinsic immunity
factor is Trim5alpha (Trim5a). Trim5a specifically recognizes capsids of retroviruses
through protein-protein interactions and restricts viral infections. The selective pressures
exerted by the viral capsid on Trim5a through these specific interactions have caused
Trim5a to be under immense adaptive evolutionary pressure during host evolution.
However, evolutionary studies looking at Trim5a in mammals show that these pressures
are episodic and not constant. Therefore the maintenance of Trim5a where these
pressures are lacking suggests additional roles for Trim5a that are independent of
retroviral capsid recognition. We identified and characterized the rodent homologs of
Trim5a. Based on the functions of the murine homologs of Trim5a we have identified
ancestral and conserved functions for Trim5a which are involved in innate immunity, cell
signaling and maintenance of retroviral latency. My research focuses on how a rapidly
evolving antiviral factor such as Trim5a is able to maintain its other cellular functions in
innate immunity and cell signaling while still being able to take part in the evolutionary arms race between host and pathogen.
September 15, 13:30, FENS 2019