Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu

Vasundhara Varthakavi, Ellen Heimann-Nichols, Rita M. Smith, Yuehui Sun, Richard J. Bram, Showkat Ali, Jeremy Rose, Lingmei Ding, Paul Spearman

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)641-647
Number of pages7
JournalNature Medicine
Volume14
Issue number6
DOIs
StatePublished - Jun 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Varthakavi, V., Heimann-Nichols, E., Smith, R. M., Sun, Y., Bram, R. J., Ali, S., Rose, J., Ding, L., & Spearman, P. (2008). Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu. Nature Medicine, 14(6), 641-647. https://doi.org/10.1038/nm1778