Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein

TY - JOUR

T1 - Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein

AU - Sheehy, A M

AU - Gaddis, N C

AU - Choi, J D

AU - Malim, M H

PY - 2002/8/8

Y1 - 2002/8/8

N2 - Viruses have developed diverse non-immune strategies to counteract host-mediated mechanisms that confer resistance to infection. The Vif (virion infectivity factor) proteins are encoded by primate immunodeficiency viruses, most notably human immunodeficiency virus-1 (HIV-1). These proteins are potent regulators of virus infection and replication and are consequently essential for pathogenic infections in vivo(1-6). HIV-1 Vif seems to be required during the late stages of virus production(3,6) for the suppression of an innate antiviral phenotype that resides in human T lymphocytes(7,8). Thus, in the absence of Vif, expression of this phenotype renders progeny virions non-infectious. Here, we describe a unique cellular gene, CEM15, whose transient or stable expression in cells that do not normally express CEM15 recreates this phenotype, but whose antiviral action is overcome by the presence of Vif. Because the Vif: CEM15 regulatory circuit is critical for HIV-1 replication, perturbing the circuit may be a promising target for future HIV/AIDS therapies.

AB - Viruses have developed diverse non-immune strategies to counteract host-mediated mechanisms that confer resistance to infection. The Vif (virion infectivity factor) proteins are encoded by primate immunodeficiency viruses, most notably human immunodeficiency virus-1 (HIV-1). These proteins are potent regulators of virus infection and replication and are consequently essential for pathogenic infections in vivo(1-6). HIV-1 Vif seems to be required during the late stages of virus production(3,6) for the suppression of an innate antiviral phenotype that resides in human T lymphocytes(7,8). Thus, in the absence of Vif, expression of this phenotype renders progeny virions non-infectious. Here, we describe a unique cellular gene, CEM15, whose transient or stable expression in cells that do not normally express CEM15 recreates this phenotype, but whose antiviral action is overcome by the presence of Vif. Because the Vif: CEM15 regulatory circuit is critical for HIV-1 replication, perturbing the circuit may be a promising target for future HIV/AIDS therapies.

UR - http://www.scopus.com/inward/record.url?scp=0037043699&partnerID=8YFLogxK

U2 - 10.1038/nature00939

DO - 10.1038/nature00939

M3 - Article

SN - 1476-4687

VL - 418

SP - 646

EP - 650

JO - NATURE

JF - NATURE

IS - 6898

ER -