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

Nat Med. 2008 Jun;14(6):641-7. doi: 10.1038/nm1778. Epub 2008 May 25.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Electroporation
  • Gene Deletion
  • Green Fluorescent Proteins / metabolism
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • HeLa Cells
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / metabolism*
  • Human Immunodeficiency Virus Proteins / ultrastructure
  • Humans
  • Ligands
  • Plasmids
  • T-Lymphocytes / ultrastructure
  • T-Lymphocytes / virology
  • Transfection
  • Viral Regulatory and Accessory Proteins / genetics
  • Viral Regulatory and Accessory Proteins / metabolism*
  • Viral Regulatory and Accessory Proteins / ultrastructure

Substances

  • Adaptor Proteins, Signal Transducing
  • CAMLG protein, human
  • Human Immunodeficiency Virus Proteins
  • Ligands
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1
  • Green Fluorescent Proteins