Live Attenuated Rev-Independent Nef-SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques

Siddappa N. Byrareddy, Mila Ayash-Rashkovsky, Victor G. Kramer, Sandra J. Lee, Mick Correll, Francis J. Novembre, Francois Villinger, Welkin E. Johnson, Agneta von Gegerfelt, Barbara K. Felber, Ruth M. Ruprecht

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background:Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef- simian immunodeficiency virus (Rev-Ind Nef-SIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges.Methodology/Principal Findings:Three groups of four RM were inoculated with Rev-Ind Nef-SIV and compared. Group 1 was inoculated 8 years prior and again 15 months before low dose intrarectal challenges with SIVsmE660. Group 2 animals were inoculated with Rev-Ind Nef-SIV at 15 months and Group 3 at 2 weeks prior to the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls. All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660. Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became superinfected with the challenge virus, in contrast to the two other vaccine groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene expression analysis showed significant upregulation of innate immune response-related chemokines and their receptors, most notably CCR5 in Group 3 animals during acute infection with Rev-Ind Nef-SIV.Conclusions/Significance:We conclude that although Rev-Ind Nef-SIV remained apathogenic, acute replication of the vaccine strain was not protective but associated with increased acquisition of heterologous mucosal SIVsmE660 challenges.

Original languageEnglish (US)
Article numbere75556
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 30 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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