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

PLoS Pathogens

Jacob D. Estes¹  Brandon F. Keele¹  Adrienne E. Swanstrom¹  Gregory Q. Del Prete¹  Vineet N. KewalRamani²  David C. Montefiori³  Celia C. LaBranche³  Jeffrey D. Lifson³  Theodora Hatziioannou⁴  Anthony Rodriguez⁵  Keyur Thummar⁵  Paul D. Bieniasz⁵  Jeannine Fode⁵  Alice Raymond⁵ 

[1] AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States of America;Center for Cancer Research, National Cancer Institute, Frederick, MD, United States of America;Department of Surgery, Duke University Medical Center, Durham, NC, United States of America;Howard Hughes Medical Institute, The Rockefeller University, New York, NY, United States of America;Laboratory of Retrovirology, The Rockefeller University, New York, NY, United States of America

关键词: Macaque;    HIV-1;    Viral replication;    Cloning;    Rhesus monkeys;    T cells;    Polymerase chain reaction;    CD coreceptors;   

DOI  :  10.1371/journal.ppat.1006572

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY