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

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 antiviral effect that is not associated with a detectable increase in chronic immune activation. © 2012 by The American Society of Hematology.