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Author Notes:

Address correspondence to Cynthia A. Derdeyn, Email: cderdey@emory.edu

We gratefully acknowledge Brandon Keele for providing SGA sequences from the SIVsmE660 VH200 challenge stock, Lori Spicer and Samantha Burton for technical assistance, and Harriet Robinson for helpful discussions.

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Subjects:

Research Funding:

HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) http://dx.doi.org/10.13039/100000060 R01-AI58706 to . HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) http://dx.doi.org/10.13039/100000060 P01-AI096187

The work was also funded by grants NIH P51-RR000165 and P51-OD011132 to the Yerkes National Primate Research Center.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Virology
  • T-CELL RESPONSES
  • HETEROSEXUAL TRANSMISSION
  • RELATIVE RESISTANCE
  • ANTIBODY-RESPONSES
  • MVA VACCINE
  • DNA PRIME
  • CHALLENGE
  • INFECTION
  • SIV
  • HIV-1

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

Tools:

Journal Title:

Journal of Virology

Volume:

Volume 90, Number 4

Publisher:

, Pages 1880-1887

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2016, American Society for Microbiology.

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