Differential restriction of human immunodeficiency virus type 2 and simian immunodeficiency virus SIVmac by TRIM5α alleles

Primate lentiviruses have narrow host ranges, due in part to their sensitivities to mammalian intracellular antiviral factors such as APOBEC3G and TRIN15 alpha. Despite the protection provided by this innate immune system, retroviruses are able to transfer between species where they can cause disease. This is true for sooty mangabey simian immunodeficiency virus, which has transferred to humans as HIV-2 and to rhesus macaques as SIVmac, where it causes AIDS. Here we examine the sensitivities of the closely related HIV-2 and S1Vmac to restriction by TRIM5 alpha. We show that rhesus TRIM5 alpha can restrict HIV-2 but not the closely related SIVmac. SIVmac has not completely escaped TRIM5 alpha, as shown by its sensitivity to distantly related TRIN15a from the New World squirrel monkey. Squirrel monkey TRIM5 alpha blocks SIVmac infection after DNA synthesis and is not saturable with restriction-sensitive virus-like particles. We map the determinant for TRIM5 alpha sensitivity to the structure in the capsid protein that recruits CypA into HIV-1 virions. We also make an SIV, mutated at this site, which bypasses restriction in all cells tested.