@article{607fc30ebc17413185d5a66618e6b832,
title = "Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu",
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.",
author = "Vasundhara Varthakavi and Ellen Heimann-Nichols and Smith, {Rita M.} and Yuehui Sun and Bram, {Richard J.} and Showkat Ali and Jeremy Rose and Lingmei Ding and Paul Spearman",
note = "Funding Information: CA-specific antibodies were a gift from S. Goff (Columbia University). A. Weiss and T. Folks (US NIH AIDS Research and Reference Program) provided HeLa, Cos-7, Jurkat E6-1 and A3.01 cells. R. Bram and D. Billadeau (Mayo Clinic) provided plasmid pCMS3.eGFP.H1p. N. Landau (New York University) provided plasmid plasmid pSV-c-MLV-env–. This research was supported by grants from Vanderbilt-Meharry Center for AIDS Research Developmental Core funded by the US NIH (to V.V.), the Vanderbilt Department of Pediatrics (to V.V.), Building Interdisciplinary Research Careers in Women{\textquoteright}s Health (to V.V.) and the US NIH (AI058828 to P.S. and 5R01CA112414 to R.J.B). We thank S.P. Goff (Columbia University) and K. Strebel (NIH) for reagents used in the study. We thank the Center for AIDS Research cell immunopathogenesis core and Emory School of Medicine EM core for help. We also thank R.T. D{\textquoteright}Aquila and H.E. Ruley for critical review of the manuscript.",
year = "2008",
month = jun,
doi = "10.1038/nm1778",
language = "English (US)",
volume = "14",
pages = "641--647",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "6",
}