HIV-1 mutates to evade IFITM1 restriction

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• 作者：Shilei Ding^a ; ^b ; Qinghua Pan^a ; Shan-Lu Liu^d ; ^{liushan@missouri.edu" class="auth_mail} ; Chen Liang^a ; ^b ; ^c ; ^{chen.liang@mcgill.ca" class="auth_mail}
• 关键词：HIV-1 ; IFITM1 ; Cell-to-cell transmission ; Escape mutations
• 刊名：Virology
• 出版年：April, 2014
• 年：2014
• 卷：454-455
• 期：Complete
• 页码：11-24
• 全文大小：2361 K

文摘

Interferon-induced transmembrane (IFITM) proteins inhibit the infection of a wide range of viruses including human immunodeficiency virus type 1 (HIV-1). At present, little is known about how viruses overcome IFITM restriction. In this study, we have utilized HIV-1 as a model and selected IFITM1-resistant viruses after multiple passages of HIV-1 in IFITM1-expressing SupT1 cells. Sequencing the entire viral genome revealed several mutations in the vpu and envelope genes, among which mutations Vpu34 and EnvG367E together enable efficient HIV-1 replication in IFITM1-expressing cells. Vpu34 introduces a stop codon at amino acid position 35 of Vpu, whereas EnvG367E changes the G367 residue at the CD4-binding site of gp120. These two mutations do not appear to overcome the downregulation of viral p24 expression caused by IFITM1, but rather enhance HIV-1 replication by promoting cell-to-cell virus transmission. Altogether, our data demonstrate that HIV-1 can mutate to evade IFITM1 restriction by increasing cell-to-cell transmission.