Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences

Lawrence J. Tartaglia, Hui Wen Chang, Benjamin C. Lee, Peter Abbink, David Ng’ang’a, Michael Boyd, Christy L. Lavine, So Yon Lim, Srisowmya Sanisetty, James B. Whitney, Michael S. Seaman, Morgane Rolland, Sodsai Tovanabutra, Jintanat Ananworanich, Merlin L. Robb, Jerome H. Kim, Nelson L. Michael, Dan H. Barouch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Simian-human immunodeficiency virus (SHIV) challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE) env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection.

Original languageEnglish
Article numbere1005431
JournalPLoS Pathogens
Issue number2
StatePublished - Feb 2016
Externally publishedYes


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