%0 Journal Article %T HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation %A Andrew Soper %A Diako Ebrahimi %A Eri Yamada %A Guillermo Juarez-Fernandez %A Kei Sato %A Miyu Moriwaki %A Naoko Misawa %A Reuben S. Harris %A Rokusuke Yoshikawa %A Shingo Iwami %A Shinji Nakaoka %A Takaaki Funo %A Yoshio Koyanagi %A Yusuke Nakano %A Yuuya Tachiki %J - %D 2017 %R 10.1371/journal.ppat.1006348 %X APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1 %K HIV-1 %K Mouse models %K T cells %K Haplotypes %K Sequence databases %K Plasmid construction %K Gene expression %K Phylogenetic analysis %U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006348