Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein.
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. HIV-1 Vif seems to be required during the late stages of virus production for the suppression of an innate antiviral phenotype that resides in human T lymphocytes. 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.
Sheehy
Ann M
AM
Department of Microbiology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Gaddis
Nathan C
NC
Choi
Jonathan D
JD
Malim
Michael H
MH
D000071480:APOBEC-3G Deaminase; D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D003001:Cloning, Molecular; D003564:Cytidine Deaminase; D017353:Gene Deletion; D016346:Gene Products, vif / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009700:Nucleoside Deaminases; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014771:Virion / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase