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Updated: Jun 13, 2026
14:23
A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
APOBEC3G contributes to HIV-1 variation through sublethal mutagenesis.
Holly A Sadler1, Mark D Stenglein, Reuben S Harris
1Institute for Molecular Virology, 18-242 Moos Tower, 515 Delaware St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
Journal of Virology
|May 14, 2010
Summary
The APOBEC3G protein causes sublethal mutations in HIV-1, leading to viable viruses. These mutations contribute to HIV-1 evolution and drug resistance.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Mammalian APOBEC3 proteins are crucial for innate immunity against retroviruses.
- APOBEC3G inhibits HIV-1 by causing lethal mutations during reverse transcription.
Purpose of the Study:
- To investigate if APOBEC3G induces sublethal mutations in HIV-1, maintaining infectivity and contributing to viral variation.
- To formally demonstrate sublethal mutagenesis by APOBEC3G on HIV-1.
Main Methods:
- Development of a novel model system using an HIV-1 vector and APOBEC3G-expressing cells.
- Analysis of proviruses for APOBEC3G-mediated mutations, including their location and impact on infectivity.
- Rescue and infectivity assays of mutated proviruses.
Main Results:
- Observed single APOBEC3G-mediated G-to-A mutations in HIV-1 proviruses, occurring at specific hot spots.
- Demonstrated that these mutated proviruses, even with APOBEC3G presence (and Vif absence), retained infectivity.
- Confirmed the induction of sublethal mutagenesis by APOBEC3G.
Conclusions:
- APOBEC3G restriction of HIV-1 can produce viable viral progeny with sublethal G-to-A mutations.
- These sublethal mutations are a potential driver of HIV-1 evolution, pathogenesis, immune escape, and drug resistance.
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