Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV

Wilkins, Jordan; Zheng, Yi-Min; Yu, Jingyou; Liang, Chen; Liu, Shan-Lu

While the various primate IFITMs are closely related and share a high degree of homology, there are several differences at the amino acid level that could account for stronger restrictive properties of some nonhuman primate IFITMs (S2 Fig). During purifying selection, changes that are deleterious to the gene function are removed from a population. In contrast, rare polymorphisms that present advantages to the population can occur and be preserved [70] . Though further investigation is needed, it is likely that polymorphisms in the IFITMs are responsible for their varying degrees of viral restriction [36, 71, 72] . It may also be that HIV/SIV Env has undergone positive selection that allows it to partially escape IFITM restriction to varying degrees [29, 51] . To date, no known viral accessory gene(s) have been identified to specifically antagonize the IFITM proteins [50] , which could explain why primate IFITMs are under purifying selection. Hence, it is likely that the differential restrictions of IFITMs lie in the functional interactions between IFITM and primate lentivirus Env proteins. Indeed, we show here that human IFITMs are capable of interacting with HIV-1 envelope and that this interaction is evolutionarily conserved for OWM IFITM3 (Fig 3) . More work is needed to elucidate the detailed mechanism(s) of IFITM restriction as well as viral countermeasures.