Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques

Abstract

The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans. The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry. However, it is still unclear to what extent the antiviral activity of IFITM3 observed in cell culture translates into inhibition of HIV/SIV spread in the infected host. We have shown previously that although rhIFITM3 inhibits SIV entry into cultured cells, polymorphisms in the rhIFITM3 gene are not strongly associated with viral load or disease progression in SIV infected macaques. Here, we examined whether rhIFITM3(2), which is closely related to rhIFITM3 at the sequence level, exerts antiviral activity and whether polymorphisms in the rhIFITM3(2) gene impact the course of SIV infection. We show that expression of rhIFITM3(2) is interferon-inducible and inhibits SIV entry into cells, although with reduced efficiency as compared to rhIFITM3. We further report the identification of 19 polymorphisms in the rhIFITM3(2) gene. However, analysis of a well characterized cohort of SIV infected macaques revealed that none of the polymorphisms had a significant impact upon the course of SIV infection. These results and our previous work suggest that polymorphisms in the rhIFITM3 and rhIFITM3(2) genes do not strongly modulate the course of SIV infection in macaques.

Interferon-Induced Transmembrane Proteins Inhibit Infection by the Kaposi’s Sarcoma-Associated Herpesvirus and the Related Rhesus Monkey Rhadinovirus in a Cell Type-Specific Manner

“…Vice versa it was also shown that primate IFITMs are effective against human viruses (69,70), in line with the high degree of conservation of IFITMs in primate species (71,72).…”

An atlas of immune cell transcriptomes in human immunodeficiency virus-infected immunological non-responders identified marker genes that control viral replication

“…[ 26 ] IFITM3, an interferon-inducible transmembrane protein, has been found to exert an inhibitory effect against HIV and simian immunodeficiency virus infection during the host cell entry phase. [ 27 ] This cytokine reduces HIV-1 infectivity through a mechanism that is not fully understood. [ 28 ] Furthermore, IFITM proteins, and in particular IFITM3, can bind with HIV-1 viruses and inhibit their fusion and cell-to-cell transmission.…”