TY - JOUR
T1 - A single gp120 residue can affect HIV-1 tropism in macaques
AU - Del Prete, Gregory Q.
AU - Keele, Brandon F.
AU - Fode, Jeannine
AU - Thumar, Keyur
AU - Swanstrom, Adrienne E.
AU - Rodriguez, Anthony
AU - Raymond, Alice
AU - Estes, Jacob D.
AU - LaBranche, Celia C.
AU - Montefiori, David C.
AU - KewalRamani, Vineet N.
AU - Lifson, Jeffrey D.
AU - Bieniasz, Paul D.
AU - Hatziioannou, Theodora
N1 - Publisher Copyright:
© 2017 Del Prete et al.
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.ppat.1006572
DO - 10.1371/journal.ppat.1006572
M3 - Article
C2 - 28945790
AN - SCOPUS:85030457870
SN - 1553-7366
VL - 13
JO - PLoS pathogens
JF - PLoS pathogens
IS - 9
M1 - e1006572
ER -