Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV

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

The IFITM proteins are capable of restricting viruses at various stages of infection [12, 13, 19, 29, 69] . We sought to determine if there was a particular stage during the HIV-1 life cycle in which nonhuman primate IFITMs inhibit HIV-1 compared to that of human IFITMs. Previously, our lab determined that human IFITMs restrict HIV-1 in part by antagonizing HIV-1 envelope [29] . In this work we found that interaction of envelope with OWM (L'Hoest's) IFITM3 was conserved (Fig 3) . However, only a slight increase (about 20%) in binding efficiency between OWM IFITM3 and HIV-1 envelope was observed (Fig 3) . However, cell-to-cell transmission data clearly demonstrated that OWM IFITM3 is more efficient than human IFITM3 to reduce HIV-1 cell-to-cell spread and prolonged viral replication (Fig 5) . These results together suggest that the main step of IFITM mediated restriction of HIV-1 occurs in the viral producer cells and is during cell-to-cell spread. It should be noted that the efficiency of HIV-1 cell-to-cell infection and replication in the presence of IFITMs are sometimes cell-type dependent [29] .