Signatures in Simian Immunodeficiency Virus SIVsmE660 Envelope gp120 Are Associated with Mucosal Transmission but Not Vaccination Breakthrough in Rhesus Macaques

• Type of Material: Article
• Authors: S. Abigail Smith, Emory University; Katie M. Kilgore, Emory University; Sudhir Kasturi, Emory University; Bali Pulendran, Emory University; Eric Hunter, Emory University; Rama Amara, Emory University; Cynthia Derdeyn, Emory University
• Language: English
• Date: 2016-02-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2016, American Society for Microbiology.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.02711-15
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 90
• Issue: 4
• Start Page: 1880
• End Page: 1887
• Grant/Funding Information: National Institute of Allergy and Infectious Diseases (NIAID) http://dx.doi.org/10.13039/100000060 R01-AI58706 to . HHS; The work was also funded by grants NIH P51-RR000165 and P51-OD011132 to the Yerkes National Primate Research Center.; NIH; National Institute of Allergy and Infectious Diseases (NIAID) http://dx.doi.org/10.13039/100000060 P01-AI096187; HHS
• Keywords: HIV-1; CHALLENGE; DNA PRIME; T-CELL RESPONSES; RELATIVE RESISTANCE; Virology; HETEROSEXUAL TRANSMISSION; Life Sciences & Biomedicine; ANTIBODY-RESPONSES; Science & Technology; SIV; INFECTION; MVA VACCINE
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology; Biology, Microbiology

Abstract

Mucosal surfaces are vulnerable to human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection and thus are key sites for eliciting vaccine-mediated protection. Vaccine protocols carried out at the Yerkes Primate Research Center utilized SIVmac239-based immunization strategies with intrarectal and intravaginal SIVsmE660 challenge of rhesus macaques. We investigated whether there were genetic signatures associated with SIVsmE660 intrarectal and intravaginal transmissions in vaccinated and unvaccinated monkeys. When transmitted/founder (T/F) envelope (Env) sequences from 49 vaccinated and 15 unvaccinated macaques were compared to each other, we were unable to identify any vaccine breakthrough signatures. In contrast,when the vaccinated and control T/F Envs were combined and compared to the challenge stock, residues at gp120 positions 23, 45, 47, and 70 (Ile-Ala-Lys-Asn [I-A-K-N]) emerged as signatures of mucosal transmission. However, T/F Envs derived from intrarectal and intravaginal infections were not different. Our data suggest that the vaginal and rectal mucosal environments both imposed a strong selection bias for SIVsmE660 variants carrying I-A-K-N that was not further enhanced by immunization.These findings, combined with the strong conservation of A-K-N in most HIV-2/SIVsmm isolates and the analogous residues in HIV-1/SIVcpz isolates, suggest that these residues confer increased transmission fitness to SIVsmE660.