Article abstract
Nature Medicine 14, 641 - 647 (2008)
Published online: 25 May 2008 | doi:10.1038/nm1778
Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu
Vasundhara Varthakavi1, Ellen Heimann-Nichols1, Rita M Smith1, Yuehui Sun1, Richard J Bram2, Showkat Ali3, Jeremy Rose3, Lingmei Ding3 & Paul Spearman3
Abstract
The HIV-1 Vpu protein is required for efficient viral release from human cells. For HIV-2, the envelope (Env) protein replaces the role of Vpu. Both Vpu and HIV-2 Env enhance virus release by counteracting an innate host-cell block within human cells that is absent in African green monkey (AGM) cells. Here we identify calcium-modulating cyclophilin ligand (CAML) as a Vpu-interacting host factor that restricts HIV-1 release. Expression of human CAML (encoded by CAMLG) in AGM cells conferred a strong restriction of virus release that was reversed by Vpu and HIV-2 Env, suggesting that CAML is the mechanistic link between these two viral regulators. Depletion of CAML in human cells eliminated the need for Vpu in enhancing HIV-1 and murine leukemia virus release. These results point to CAML as a Vpu-sensitive host restriction factor that inhibits HIV release from human cells. The ability of CAML to inhibit virus release should illuminate new therapeutic strategies against HIV.
- Department of Pediatrics, Division of Infectious Diseases, Vanderbilt University School of Medicine, 1161 21st Avenue South, D-7235 MCN, Nashville, Tennessee 37232-2581, USA.
- Department of Pediatric and Adolescent Medicine, Division of Pediatric Research Laboratories, Mayo Clinic, Mayo Medical School, 200 First Street Southwest, Rochester, Minnesota 55905, USA.
- Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, 2015 Upper Gate Drive, Atlanta, Georgia 30322, USA.
Correspondence to: Vasundhara Varthakavi1 e-mail: vasundhara.varthakavi@vanderbilt.edu
Correspondence to: Paul Spearman3 e-mail: paul.spearman@emory.edu
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