Natural resistance to HIV infection: The Vif-APOBEC interaction.
Members of the APOBEC family of cellular polynucleotide cytidine deaminases (e.g., APOBEC3G) are potent inhibitors of HIV infection. Wild type viral infections are largely spared from APOBEC function through the action of the viral Vif protein. In Vif's absence, inhibitory APOBEC proteins are encapsidated by budding virus particles leading to excessive cytidine (C) to uridine (U) hypermutation of negative sense reverse transcripts in newly infected cells. This registers as guanosine (G) to adenosine (A) mutations in plus stranded cDNA. Because the functions of Vif and APOBEC proteins oppose each other, it is likely that fluctuations in the Vif/APOBEC balance can influence the natural history of HIV infection. Experimental support for this notion would further justify and stimulate drug discovery initiatives in this area.
Malim
Michael H
MH
Department of Infectious Diseases, King's College London, School of Medicine, 2nd Floor, New Guy's House, Guy's Hospital, London Bridge, London SE1 9RT, UK. michael.malim@kcl.ac.uk
D000071479:APOBEC-1 Deaminase; D000818:Animals; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003641:Deamination; D016346:Gene Products, vif / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D009154:Mutation; D010641:Phenotype; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D018076:DNA, Complementary; D016346:Gene Products, vif; D054320:vif Gene Products, Human Immunodeficiency Virus; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase