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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container_issue 9
container_start_page e1006572
container_title PLoS pathogens
container_volume 13
creator 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
description 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.
doi_str_mv 10.1371/journal.ppat.1006572
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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. 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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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c661t-3e89e222c532b6e5ecde0ca4c3be5a88352f62752a1f9444b260fc86334c3d753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Adaptation</topic><topic>Adaptation, Physiological - physiology</topic><topic>AIDS</topic><topic>Amino acids</topic><topic>Animal models</topic><topic>Animals</topic><topic>Binding sites</topic><topic>Biology and life sciences</topic><topic>Biomedical research</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>CD4 antigen</topic><topic>CD4 Antigens - metabolism</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Glycoprotein gp120</topic><topic>Glycoproteins</topic><topic>HIV</topic><topic>HIV Envelope Protein gp120 - chemistry</topic><topic>HIV Envelope Protein gp120 - genetics</topic><topic>HIV Infections - genetics</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - physiology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Infections</topic><topic>Laboratories</topic><topic>Macaca mulatta</topic><topic>Macaca nemestrina</topic><topic>Macaques</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Monkeys &amp; 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subjects Acquired immune deficiency syndrome
Adaptation
Adaptation, Physiological - physiology
AIDS
Amino acids
Animal models
Animals
Binding sites
Biology and life sciences
Biomedical research
Cancer
Care and treatment
CD4 antigen
CD4 Antigens - metabolism
Disease Models, Animal
Female
Flow Cytometry
Glycoprotein gp120
Glycoproteins
HIV
HIV Envelope Protein gp120 - chemistry
HIV Envelope Protein gp120 - genetics
HIV Infections - genetics
HIV Infections - virology
HIV-1 - physiology
Human immunodeficiency virus
Humans
Immunoblotting
Infections
Laboratories
Macaca mulatta
Macaca nemestrina
Macaques
Male
Medical research
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title A single gp120 residue can affect HIV-1 tropism in macaques
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