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Published on: August 31, 2014
APOBEC3G complexes decrease human immunodeficiency virus type 1 production
Kenneth L Martin1, Megan Johnson, Richard T D'Aquila
1Division of Infectious Disease, Department of Medicine, Vanderbilt University School of Medicine, AA-2205E Medical Center North, Nashville, TN 37232-2358, USA.
APOBEC3G (A3G) complexes in producer cells reduce human immunodeficiency virus type 1 (HIV-1) production. HIV-1 virion infectivity factor (Vif) counteracts this effect by degrading A3G.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- APOBEC3G (A3G) is a host antiviral factor that restricts human immunodeficiency virus type 1 (HIV-1) replication.
- HIV-1 virion infectivity factor (Vif) antagonizes A3G by targeting it for proteasomal degradation.
- A3G can form cytoplasmic complexes in producer cells, but their functional impact on HIV-1 replication is unclear.
Purpose of the Study:
- To investigate the functional effects of APOBEC3G (A3G) complexes in producer cells on HIV-1 replication.
- To determine if A3G complexes influence HIV-1 particle production and viral Gag protein stability.
Main Methods:
- HeLa cells were cotransfected with HIV-1 constructs and either wild-type A3G or mutant A3G forms.
- A3G complex formation, pseudovirus particle production, and intracellular HIV-1 Gag half-life were assessed.
- T cell lines (CEM and CEM-SS) were used to evaluate HIV-1 replication with or without Vif and A3G complexes.
Main Results:
- Cells expressing A3G that formed complexes showed decreased pseudovirus particle production compared to cells with non-complex-forming A3G mutants.
- Intracellular HIV-1 Gag half-life was significantly shorter in cells containing A3G complexes.
- HIV-1 virion output was reduced in T cells with A3G complexes when infected with Vif-negative HIV-1.
Conclusions:
- Endogenous APOBEC3G (A3G) complexes in producer cells significantly decrease HIV-1 production.
- The formation of A3G complexes impacts HIV-1 Gag stability and virion output.
- HIV-1 virion infectivity factor (Vif) counteracts the inhibitory effect of A3G complexes by promoting A3G degradation.
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