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

Abstract:

: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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Del Prete GQ,Keele BF,Fode J,Thummar K,Swanstrom AE,Rodriguez A,Raymond A,Estes JD,LaBranche CC,Montefiori DC,KewalRamani VN,Lifson JD,Bieniasz PD,Hatziioannou T

doi

10.1371/journal.ppat.1006572

subject

Has Abstract

pub_date

2017-09-25 00:00:00

pages

e1006572

issue

9

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-17-00711

journal_volume

13

pub_type

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