Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.

TitleSelection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.
Publication TypeJournal Article
Year of Publication2014
AuthorsDel Prete GQ, Ailers B, Moldt B, Keele BF, Estes JD, Rodriguez A, Sampias M, Oswald K, Fast R, Trubey CM, Chertova E, Smedley J, Labranche CC, Montefiori DC, Burton DR, Shaw GM, Markowitz M, Piatak M, KewalRamani VN, Bieniasz PD, Lifson JD, Hatziioannou T
JournalCell Host Microbe
Volume16
Issue3
Pagination412-8
Date Published09/10/2014
ISSN1934-6069
Abstract

Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.

DOI10.1016/j.chom.2014.08.003
Alternate JournalCell Host Microbe
PubMed ID25211081
PubMed Central IDPMC4268878
Grant ListHHSN261200800001E / / PHS HHS / United States
HHSN27201100016C / / PHS HHS / United States
R01 AI094604 / AI / NIAID NIH HHS / United States
R01AI50111 / AI / NIAID NIH HHS / United States
R21 AI093255 / AI / NIAID NIH HHS / United States
R21AI093255 / AI / NIAID NIH HHS / United States
R33 AI087383 / AI / NIAID NIH HHS / United States
R37 AI064003 / AI / NIAID NIH HHS / United States
R37AI64003 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
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