Transcriptional profiling of peripheral CD8+T cell responses to SIVΔnef and SIVmac251 challenge reveals a link between protective immunity and induction of systemic immunoregulatory mechanisms

Abstract Immunization of macaques with attenuated simian immunodeficiency virus (SIV) with deletions in nef (SIVΔnef) is shown to elicit protective immunity to infection by pathogenic SIV, yet the mechanisms that orchestrate protection and prevent pathogenesis remains unknown. We utilized whole-geno...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2014-11, Vol.468, p.581-591
Main Authors: George, Michael D, Hu, William, Billingsley, James M, Reeves, R. Keith, Sankaran-Walters, Sumathi, Johnson, R. Paul, Dandekar, Satya
Format: Article
Language:English
Subjects:
Animals
CD8+T cell response
CD8-Positive T-Lymphocytes - physiology
Female
Gene expression
Gene Expression Regulation, Viral - physiology
HIV
Immune activation
Immune regulation
Immunization
Infectious Disease
Macaca mulatta
Microarray
Receptors, Cell Surface
SAIDS Vaccines - immunology
Simian immunodeficiency virus
Simian Immunodeficiency Virus - physiology
SIV
Transcriptome
Vaccine
Viral Load
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Summary:Abstract Immunization of macaques with attenuated simian immunodeficiency virus (SIV) with deletions in nef (SIVΔnef) is shown to elicit protective immunity to infection by pathogenic SIV, yet the mechanisms that orchestrate protection and prevent pathogenesis remains unknown. We utilized whole-genome transcriptional profiling to reveal molecular signatures of protective immunity in circulating CD8+ T cells of rhesus macaques vaccinated with SIVmac239Δnef and challenged with pathogenic SIVmac251. Our findings suggest that protective immunity to pathogenic SIV infection induced by SIVmac239∆nef is associated with balanced induction of T cell activation and immunoregulatory mechanisms and dampened activation of interferon-induced signaling pathways and cytolytic enzyme production as compared with pathogenic SIVmac251 infection of unvaccinated controls. We provide evidence that protective immunity to SIVmac251 correlates with induction of biomarkers of T cell activation, differentiation, signaling, and adhesion that were down regulated in unvaccinated controls. The study highlights potential immunomodulatory networks associated with protective immunity against the virus.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2014.09.013