Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu.
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.
Varthakavi
Vasundhara
V
Department of Pediatrics, Division of Infectious Diseases, Vanderbilt University School of Medicine, 1161 21st Avenue South, D-7235 MCN, Nashville, Tennessee 37232-2581, USA. vasundhara.varthakavi@vanderbilt.edu
Heimann-Nichols
Ellen
E
Smith
Rita M
RM
Sun
Yuehui
Y
Bram
Richard J
RJ
Ali
Showkat
S
Rose
Jeremy
J
Ding
Lingmei
L
Spearman
Paul
P
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D018274:Electroporation; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008024:Ligands; D010957:Plasmids; D013601:T-Lymphocytes / Q000648:ultrastructure / Q000821:virology; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000086082:Viroporin Proteins
D048868:Adaptor Proteins, Signal Transducing; D049452:Green Fluorescent Proteins; D054298:Human Immunodeficiency Virus Proteins; D008024:Ligands; D054334:Viral Regulatory and Accessory Proteins; C089404:CAMLG protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins