Vif-mediated degradation of APOBEC3G

Stable Identifier
R-HSA-180585
Type
Pathway
Species
Homo sapiens
Related Species
Human immunodeficiency virus 1
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The HIV-1 accessory protein Vif (Viral infectivity factor) is required for the efficient infection of primary cell populations (e.g., lymphocytes and macrophages) and 'non-permissive' cell lines. Vif neutralises the host DNA editing enzyme, APOBEC3G, in the producer cell. Indeed, in the absence of a functional Vif, APOBEC3G is selectively incorporated into the budding virions and in the next cycle of infection leads to the deamination of deoxycytidines (dC) within the minus-strand cDNA during reverse transcription (Sheehy et al 2003; Li et al., 2005 ; Stopak et al. 2003).
Deamination changes cytidine to uracil and thus results in G to A transitions and stop codons in the provirus. The aberrant cDNAs produced in the infected cell can either be integrated in form of non-functional proviruses or degraded. Vif counteracts the antiviral activity of APOBEC3G by associating directly with it and promoting its polyubiquitination and degradation by the 26S proteasome.
Vif binds APOBEC3G and recruits it into an E3 ubiquitin-enzyme complex composed by the cytoplasmic proteins Cullin5, Rbx, ElonginC and ElonginB (Yu et al., 2003) . Thus, in the presence of Vif, APOBEC3G incorporation into the virion is minimal.

Literature References
PubMed ID Title Journal Year
14564014 Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex

Yu, X, Yu, Y, Liu, B, Luo, K, Kong, W, Mao, P, Yu, XF

Science 2003
15781449 Ubiquitination of APOBEC3G by an HIV-1 Vif-Cullin5-Elongin B-Elongin C complex is essential for Vif function

Kobayashi, M, Takaori-Kondo, A, Miyauchi, Y, Iwai, K, Uchiyama, T

J Biol Chem 2005
14528300 The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif

Sheehy, AM, Gaddis, NC, Malim, MH

Nat Med 2003
Participants
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Disease
Name Identifier Synonyms
Human immunodeficiency virus infectious disease 526 HIV infection
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Created