HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation

Nature Medicine, 2003; 9: 1398-1403

Speaker：張美蘭                       Place：601

Commentator：陳舜華 老師                  Date：2003/11/19 15:00-16:00

Abstract：

Vif (viral infectivity factor) is necessary for HIV-1 replication in nonpermissive cells, like human T lymphocytes. Vif protein can neutralize antiviral pathway in nonpermissive cells by degrading APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic peptide like 3G). APOBEC3G which only presents in nonpermissive cells, causes cytidine deamination in RNA editing and it is an endogenous inhibitor in HIV-1 virus. In the absence of Vif, △vif, APOBEC3G has an antiviral activity of the negative strand of the HIV-1 cDNA during reverse transcription.Vif-deficient viruses can attach to and penetrate host cells but do not have the ability to infect the next cell.  Vif protein has two domains: one binds to APOBEC3G and the other regulates the degradation of APOBEC3G by a conserved sequence, SLQ (Y/F) LA motif. Vif protein induces rapid degradation of APOBEC3G by ubiquitination, that is a proteosome dependent pathway. Proteosome inhibitor, like ALLN or MG132 will increase the extent of APOBEC3G expression in wild type HIV-1. So APOBEC3G will be the therapeutic way for HIV-1 in the future. Drugs can be designed for a conversed sequence, SLQ (Y/F) LA motif in Vif protein. So that SLQ (Y/F) LA motif can’t degrade APOBEC3G, lead to APOBEC3G has an antivirus activity.

Reference：

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