A single gp120 residue can affect HIV-1 tropism in macaques

Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express H...

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Veröffentlicht in:PLoS pathogens 2017-09, Vol.13 (9), p.e1006572
Hauptverfasser: Del Prete, Gregory Q, Keele, Brandon F, Fode, Jeannine, Thummar, Keyur, Swanstrom, Adrienne E, Rodriguez, Anthony, Raymond, Alice, Estes, Jacob D, LaBranche, Celia C, Montefiori, David C, KewalRamani, Vineet N, Lifson, Jeffrey D, Bieniasz, Paul D, Hatziioannou, Theodora
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Sprache:eng
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Zusammenfassung:Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env) glycoproteins, (SHIVs) and simian-tropic HIV-1 (stHIV) strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1006572