TY - JOUR T1 - Live Attenuated Rev-Independent Nef¯SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques A1 - Byrareddy, Siddappa N. A1 - Ayash-Rashkovsky, Mila A1 - Kramer, Victor G. A1 - Lee, Sandra J. A1 - Correll, Mick A1 - Novembre, Francis J. A1 - Villinger, Francois A1 - Johnson, Welkin E. A1 - von Gegerfelt, Agneta A1 - Felber, Barbara K. A1 - Ruprecht, Ruth M. Y1 - 2013/09/30 N2 - BackgroundRhesus 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 FindingsThree 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/SignificanceWe 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. JF - PLOS ONE JA - PLOS ONE VL - 8 IS - 9 UR - https://doi.org/10.1371/journal.pone.0075556 SP - e75556 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pone.0075556 ER -