Primate lentiviruses are differentially inhibited by interferon-induced transmembrane proteins

Abstract

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 (SIVAGM) being mostly restricted by human IFITM2. Interestingly, SIVAGM 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 SIVAGM 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.

The Interferon-Stimulated GeneIfitm3Restricts West Nile Virus Infection and Pathogenesis

“…Based primarily on studies in cell culture, the ISG IFITM3 has been suggested to have antiviral activity against a variety of viral pathogens, including flaviviruses (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). A demonstrable antiviral role for IFITM3/Ifitm3 in vivo has been established previously only for IAV and RSV (3,43,45,46).…”

“…Although initial studies described possible roles of IFITM1, IFITM2, and IFITM3 in development, apoptosis, cell proliferation, and cell signaling (5)(6)(7)(8)(9)(10)(11)(12)(13), a subsequent report suggested that ectopic expression of IFITM1 in mouse L cells could restrict infection of vesicular stomatitis virus (VSV) (14). A decade later, gene silencing and ectopic expression studies established that IFITM proteins have antiviral activity in cell culture against members of the Flaviviridae, Orthomyxoviridae, Filoviridae, Rhabdoviridae, Retroviridae, Bunyaviridae, Reoviridae, Togaviridae, and Paramyxoviridae families (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Nonetheless, some enveloped and nonenveloped viruses appear to be resistant to the actions of IFITM proteins, including arenaviruses, papillomaviruses, cytomegaloviruses, and adenoviruses (16,17,29).…”

Human, Pig, and Mouse Interferon-Induced Transmembrane Proteins Partially Restrict Pseudotyped Lentiviral Vectors

“…In fact, studies suggest that amphotericin B may provide such a reagent. 35,36 Using technologies such as the Connectivity Map, 37 gene expression profiles from cells with and without IFITM expression could be used as queries to identify candidate drugs for screening in future work. Transient knockdown of IFITMs, using small interfering RNA (siRNA) technologies, is a less appealing strategy because of the resulting interferon stimulation that simultaneously augments antiviral defenses, including IFITMs.…”

The V3 Loop of HIV-1 Env Determines Viral Susceptibility to IFITM3 Impairment of Viral Infectivity

“…A number of different viral envelopes, including those of murine leukemia virus (MLV), Lassa virus, Machupo virus, and lymphocytic choriomeningitis virus, are relatively resistant to the inhibition of IFITM proteins when they are expressed in target cells (1). Different HIV and simian immunodeficiency virus (SIV) strains also show different degrees of susceptibility to IFITM inhibition in target cells (26,27). However, it is not known whether any viral envelopes resist the inhibition of IFITM proteins that are incorporated into virus particles.…”