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

• Type of Material: Article
• Authors: Siddappa N. Byrareddy, Emory University; Mila Ayash-Rashkovsky, Dana-Farber Cancer Institute; Victor Kramer, Dana-Farber Cancer Institute; Sandra Lee, Dana-Farber Cancer Institute; Mick Correll, Dana-Farber Cancer Institute; Francis Novembre, Emory University; Francois Villinger, Emory University; Welkin Johnson, Boston College; Agneta von Gegerfelt, Center for Cancer Research; Barbara Felber, Center for Cancer Research; Ruth Ruprecht, Dana-Farber Cancer Institute
• Language: English
• Date: 2013
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075556
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 9
• Start Page: e75556
• End Page: e75556
• Grant/Funding Information: This project was also funded by the National Center for Research Resources grant P51RR169 and is currently supported by the Office of Research Infrastructure Programs/OD P51OD11107.; This study was supported by National Institutes of Health grants R01 RR014180, P01 AI048240 to RMR, NIH R01 AI083118 to WEJ, and the Intramural Research Program of the National Cancer Institute, NIH to BKF.
• Research Categories: Biology, Virology; Health Sciences, Pathology; Health Sciences, Immunology

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.