Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV

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

IFITM proteins have been characterized as restriction factors as they are interferon inducible and restrict many enveloped viruses. Herein, we show that primate IFITMs have undergone purifying or negative selection suggesting that primate IFITMs are atypical restriction factors that are not directly antagonized by viruses. In this study, we determined the sequence for 14 new nonhuman primate IFITMs from Gorilla, L'Hoest's, Moustached, Sykes, Mangabey, Mandrill, and Guereza and demonstrated that primate IFITMs have undergone purifying selection rather than positive selection. Negative selection of primate IFITMs would suggest they have not been highly antagonized by viruses; to date there are no known viral antagonists that directly target the IFITMs. These results may suggest that the primate IFITMs contain an ancient primary function that is not involved in viral restriction. Indeed, IFITMs have been implicated in several cellular functions including immunity, germ cell development, cell adhesion, oncogenesis, bone mineralization, proliferation and cell death [21, [65] [66] [67] [68] . Furthermore, in the absence of IFN, IFITM proteins have been shown to be basally expressed in cells (including gorilla fibroblasts, Fig 6A) [65] .