Impact of suboptimal APOBEC3G neutralization on the emergence of HIV drug resistance in humanized mice

HIV diversification facilitates immune escape and complicates antiretroviral therapy. Both viral (e.g., reverse transcriptase, RT) and host factors (e.g., APOBEC3G (A3G)) can introduce mutations into HIV genomes which can drive viral evolution. However, the contribution of APOBEC3 mutagenesis to viral diversification is not well understood in vivo. Recent studies demonstrate humanized mouse models combined with deep sequencing approaches enable high resolution characterization of HIV dynamics. Here we utilized Illumina MiSeq technology and unique molecular IDs to quantitatively examine the evolving HIV quasispecies over time in plasma of humanized mice infected with distinct NL4-3 clones that differ in abilities to neutralize A3G (e.g., HIV-WT, HIV-45G (Vif-E45G)).