Specific incorporation of cyclophilin A into HIV-1 virions.
Little is known about host factors necessary for retroviral virion assembly or uncoating. We have previously shown that the principal structural protein of the human immunodeficiency virus HIV-1, the Gag polyprotein, binds the cyclophilin peptidyl-prolyl isomerases; cyclophilins catalyse a rate-limiting step in protein folding and protect cells from heat shock. Here we demonstrate that cyclophilin A is specifically incorporated into HIV-1 virions but not into virions of other primate immunodeficiency viruses. A proline-rich region conserved in all HIV-1 Gag polyproteins is required for cyclophilin A binding and incorporation. Disruption of a single proline blocks the Gag-cyclophilin interaction in vitro, prevents cyclophilin A incorporation into virions, and inhibits HIV-1 replication. Our results indicate that the interaction of Gag with cyclophilin A is necessary for the formation of infectious HIV-1 virions.
Franke
E K
EK
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Yuan
H E
HE
Luban
J
J
D000591:Amino Acid Isomerases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D019696:Peptidylprolyl Isomerase; D015302:Simian Immunodeficiency Virus / Q000378:metabolism; D014162:Transfection; D014771:Virion / Q000378:metabolism*; D014779:Virus Replication
D002352:Carrier Proteins; D015683:Gene Products, gag; D009838:Oligodeoxyribonucleotides; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase