Primate lentiviruses are differentially inhibited by interferon-induced transmembrane proteins

Interferon-induced transmembrane (IFITM) proteins inhibit the entry of a large number of viruses. Not surprisingly, many viruses are refractory to this inhibition. In this study, we report that different strains of HIV and SIV are inhibited by human IFITM proteins to various degrees, with SIV of African green monkeys (SIV(AGM)) being mostly restricted by human IFITM2. Interestingly, SIV(AGM) is as much inhibited by human IFITM2 as by IFITM3 of its own host African green monkeys. Our data further demonstrate that the entry of SIV(AGM) is impaired by human IFITM2 and that this inhibition is overcome by the cholesterol-binding compound amphotericin B that also overcomes IFITM inhibition of influenza A viruses. These results suggest that IFITM proteins exploit similar mechanisms to inhibit the entry of both pH-independent primate lentiviruses and the pH-dependent influenza A viruses.