期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：27
页码：7112-7117
DOI：10.1073/pnas.1619640114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：CCR5 (R5)-tropic, but not CXCR4 (X4)-tropic, HIV-1 is associated with primary HIV-1 infection and transmission. Recent studies have shown that IFN-induced transmembrane (IFITM) proteins, including IFITM1, IFITM2, and IFITM3, restrict a broad range of viruses. Here, we demonstrate that an IFITM2 isoform (Δ20 IFITM2) lacking 20 amino acids at the N terminus differentially restricts X4 and R5 HIV-1. Δ20 IFITM2 suppresses replication of X4 HIV-1 strains by inhibiting their entry. High levels of Δ20 IFITM2 expression could be detected in CD4+ T cells and in monocytes. Infection of X4 viruses in monocyte-derived macrophages and dendritic cells is enhanced upon depletion of IFITM2 isoforms. Furthermore, we also show that coreceptor use is the determining factor for differential HIV-1 restriction of Δ20 IFITM2. When we replace the C terminus of CCR5 with the C terminus of CXCR4, R5 viruses become more susceptible to Δ20 IFITM2-mediated restriction. In contrast to previous studies, our research reveals that neither X4 nor R5 HIV-1 is suppressed by IFITM2 and IFITM3. The multifactor gatekeeping model has been proposed to explain restriction of X4 viruses in the early stage of HIV-1 diseases. Our findings indicate that Δ20 IFITM2 may serve as a major contributor to this gatekeeping mechanism.
关键词：Δ20 IFITM2 ; gatekeeping ; HIV ; interferon-inducible transmembrane protein ; viral entry
