Protecting APOBEC3G: a potential new target for HIV drug discovery.
Human immune cells possess a built-in mechanism that could potentially block the replication of retroviruses such as HIV-1. This protective mechanism centers on apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), a DNA-editing enzyme produced by host cells infected by certain retroviruses that is then incorporated into virions. Due to its cytidine deaminase activity, APOBEC3G is able to mutate the minus-strand DNA formed during reverse transcription. These events ultimately halt completion of the HIV life cycle. Unfortunately, HIV-1 encodes a protein termed virion infectivity factor (Vif) that specifically suppresses the activity of APOBEC3G. Vif achieves this effect by depleting the intracellular stores of APOBEC3G, thus making this antiviral enzyme unavailable for incorporation into budding virions. APOBEC3G depletion involves the recruitment of a specific E3 ligase complex by Vif leading to the polyubiquitylation and proteasome-mediated degradation of this enzyme. The potent activity of APOBEC3G has led to considerable interest in the identification of small molecules that interrupt the Vif-induced degradative process.
Stopak
Kimberly
K
Gladstone Institute of Virology and Immunology, University of California, San Francisco, 1650 Owens Street, San Francisco, CA 9418, USA.
Greene
Warner C
WC
D000071480:APOBEC-3G Deaminase; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D003564:Cytidine Deaminase; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D009700:Nucleoside Deaminases; D011506:Proteins / Q000187:drug effects* / Q000502:physiology; D012097:Repressor Proteins
D019380:Anti-HIV Agents; D011506:Proteins; D012097:Repressor Proteins; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase