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

PLoS Pathogens

Lawrence J. Tartaglia¹  Hui-Wen Chang¹  Benjamin C. Lee¹  James B. Whitney¹  Peter Abbink¹  David Ng’ang’a¹  Christy L. Lavine¹  Michael Boyd¹  So-Yon Lim¹  Srisowmya Sanisetty¹  Morgane Rolland¹  Sodsai Tovanabutra²  Michael S. Seaman²  Nelson L. Michael³  Jintanat Ananworanich³  Dan H. Barouch³  Jerome H. Kim³  Merlin L. Robb³ 

[1] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America;Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America;U.S. Government Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America

关键词: HIV-1;    Rhesus monkeys;    Viral load;    CCR5 coreceptor;    Coreceptors;    Viral replication;    SIV;    Vaccines;   

DOI  :  10.1371/journal.ppat.1005431

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY