An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein.
The vif gene of human immunodeficiency virus type 1 (HIV-1) encodes a basic Mr 23,000 protein that is necessary for production of infectious virions by nonpermissive cells (human lymphocytes and macrophages) but not by permissive cells such as HeLa-CD4. It had been proposed that permissive cells may contain an unidentified factor that functions like the viral Vif protein. To test this hypothesis, we produced pseudotyped wild-type and vif-deleted HIV gpt virions (which contain the HIV-1 genome with the bacterial mycophenolic acid resistance gene gpt in place of the viral env gene) in permissive cells, and we used them to generate nonpermissive H9 leukemic T cells that express these proviruses. We then fused these H9 cells with permissive HeLa cells that express the HIV-1 envelope glycoprotein gp120-gp41, and we asked whether the heterokaryons would release infectious HIV gpt virions. The results clearly showed that the vif-deleted virions released by the heterokaryons were noninfectious whereas the wild-type virions were highly infectious. This strongly suggests that nonpermissive cells, the natural targets of HIV-1, contain a potent endogenous inhibitor of HIV-1 replication that is overcome by Vif.
Madani
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Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA.
Kabat
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D000818:Animals; D000998:Antiviral Agents / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D019556:COS Cells; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D017353:Gene Deletion; D016346:Gene Products, vif / Q000235:genetics / Q000502:physiology*; D016341:Genes, vif; D005816:Genetic Complementation Test; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000276:immunology* / Q000821:virology*; D014774:Virulence / Q000235:genetics / Q000502:physiology; D054320:vif Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D016346:Gene Products, vif; D054320:vif Gene Products, Human Immunodeficiency Virus