Treatment of SIV-infected sooty mangabeys with a type-I IFN agonist results in decreased virus replication without inducing hyperimmune activation.

TitleTreatment of SIV-infected sooty mangabeys with a type-I IFN agonist results in decreased virus replication without inducing hyperimmune activation.
Publication TypeJournal Article
Year of Publication2012
AuthorsVanderford TH, Slichter C, Rogers KA, Lawson BO, Obaede R, Else JG, Villinger F, Bosinger SE, Silvestri G
JournalBlood
Volume119
Issue24
Pagination5750-7
Date Published2012 Jun 14
ISSN1528-0020
KeywordsAnimals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Cercocebus atys, Gene Expression Regulation, Humans, Interferon Type I, Lymphocyte Activation, Lymphocyte Depletion, Macaca mulatta, Recombinant Proteins, Simian Acquired Immunodeficiency Syndrome, Simian immunodeficiency virus, Species Specificity, Viral Load, Viremia, Virus Replication
Abstract

A key feature differentiating nonpathogenic SIV infection of sooty mangabeys (SMs) from pathogenic HIV/SIV infections is the rapid resolution of type I IFN (IFN-I) responses and IFN-stimulated gene expression during the acute-to-chronic phase transition and the establishment of an immune quiescent state that persists throughout the chronic infection. We hypothesized that low levels of IFN-I signaling may help to prevent chronic immune activation and disease progression in SIV-infected SMs. To assess the effects of IFN-I signaling in this setting, in the present study, we administered recombinant rhesus macaque IFNα2-IgFc (rmIFNα2) to 8 naturally SIV-infected SMs weekly for 16 weeks. Gene-expression profiling revealed a strong up-regulation of IFN-stimulated genes in the blood of treated animals, confirming the reagent's bioactivity. Interestingly, we observed an approximately 1-log decrease in viral load that persisted through day 35 of treatment. Flow cytometric analysis of lymphocytes in the blood, lymph nodes, and rectal biopsies did not reveal a significant decline of CD4(+) T cells, a robust increase in lymphocyte activation, or change in the level of SIV-specific CD8(+) T cells. The results of the present study indicate that administration of type I IFNs in SIV-infected SMs induces a significant anti-viral effect that is not associated with a detectable increase in chronic immune activation.

DOI10.1182/blood-2012-02-411496
Alternate JournalBlood
PubMed ID22550346