174 TRIM5a: A Mediator of Innate Intracellular Immunity to Retroviruses M Stremlau1, B Song1, M Perron1, C Owens1, C Owens, H Javanbakht1, W Ulm2, R Mulligan2, B Gold3, C O'hUigin3, C Winkler4, C Winkler, C Winkler, M Dean3, and Joseph Sodroski*1 1Dana-Farber Cancer Inst, Boston, MA, USA; 2Children's Hosp, Harvard Med Sch, Boston, MA, USA ; 3NCI, Frederick, MD, USA; and 4SAIC-Frederick, MD, USA

Several retroviruses, including human and simian immunodeficiency viruses and N-tropic murine leukemia viruses, encounter early blocks after entering the cells of particular primate species.  These blocks are mediated by TRIM5a, which targets the viral capsid.  TRIM5a consists of RING, B-box 2, coiled coil and B30.2(SPRY) domains.  Variation among the TRIM5a orthologues of different primate species is found in all domains, but is most dramatic in the B30.2(SPRY) domain.  Length polymorphism as well as amino acid variation is found in four regions (v1 - v4) of the TRIM5a B30.2 domain.  Episodic length expansion of v1 occurred during the evolution of Old World primates, whereas length expansion of v3 occurred during New World primate evolution.  In some species, this length expansion involves tandem duplications or triplications.  The estimated time periods during which these expansions occurred correspond to periods in which new endogenous retrovirus sequences appeared in primates.  Functional studies of TRIM5a chimerae support the importance of the B30.2 v1 region in antiretroviral potency.  Thus, lineage-specific variation among primate TRIM5a proteins accounts for different abilities to restrict particular retroviruses.