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Title

HIV-1 adapts to replicate in cells expressing common marmoset APOBEC3G and BST2

AuthorsFernández-Oliva, Alberto; Finzi, Andrés; Haim, Hillel; Menéndez-Arias, Luis ; Sodroski, Joseph; Pacheco, Beatriz
Issue Date28-Oct-2016
PublisherAmerican Society for Microbiology
CitationJournal of Virology 90: 725- 740 (2016)
AbstractPrevious studies have shown that a major block to HIV-1 replication in common marmosets operates at the level of viral entry and that this block can be overcome by adaptation of the virus in tissue-cultured cells. However, our current studies indicate that HIV-1 encounters additional postentry blocks in common marmoset peripheral blood mononuclear cells. Here, we show that the common marmoset APOBEC3G (A3G) and BST2 proteins block HIV-1 in cell cultures. Using a directed-evolution method that takes advantage of the natural ability of HIV-1 to mutate during replication, we have been able to overcome these blocks in tissue-cultured cells. In the adapted viruses, specific changes were observed in gag, vif, env, and nef. The contribution of these changes to virus replication in the presence of the A3G and BST2 restriction factors was studied. We found that certain amino acid changes in Vif and Env that arise during adaptation to marmoset A3G and BST2 allow the virus to replicate in the presence of these restriction factors. The changes in Vif reduce expression levels and encapsidation of marmoset APOBEC3G, while the changes in Env increase viral fitness and discretely favor cell-to-cell transmission of the virus, allowing viral escape from these restriction factors
URIhttp://hdl.handle.net/10261/151557
DOI10.1128/JVI.02431-15
Identifiersdoi: 10.1128/JVI.02431-15
issn: 1098-5514
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