IFN-α blockade during ART-treated SIV infection lowers tissue vDNA, rescues immune function, and improves overall health

Louise A. Swainson, Ashish Arunkumar Sharma, Khader Ghneim, Susan Pereira Ribeiro, Peter Wilkinson, Richard M. Dunham, Rebecca G. Albright, Samson Wong, Jacob D. Estes, Michael Piatak, Steven G. Deeks, Peter W. Hunt, Rafick Pierre Sekaly, Joseph M. McCune

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Type I IFNs (TI-IFNs) drive immune effector functions during acute viral infections and regulate cell cycling and systemic metabolism. That said, chronic TI-IFN signaling in the context of HIV infection treated with antiretroviral therapy (ART) also facilitates viral persistence, in part by promoting immunosuppressive responses and CD8+ T cell exhaustion. To determine whether inhibition of IFN-α might provide benefit in the setting of chronic, ART-treated SIV infection of rhesus macaques, we administered an anti-IFN-α antibody followed by an analytical treatment interruption (ATI). IFN-α blockade was well-tolerated and associated with lower expression of TIIFN- inducible genes (including those that are antiviral) and reduced tissue viral DNA (vDNA). The reduction in vDNA was further accompanied by higher innate proinflammatory plasma cytokines, expression of monocyte activation genes, IL-12-induced effector CD8+ T cell genes, increased heme/metabolic activity, and lower plasma TGF-β levels. Upon ATI, SIV-infected, ART-suppressed nonhuman primates treated with anti-IFN-α displayed lower levels of weight loss and improved erythroid function relative to untreated controls. Overall, these data demonstrated that IFN-α blockade during ART-treated SIV infection was safe and associated with the induction of immune/ erythroid pathways that reduced viral persistence during ART while mitigating the weight loss and anemia that typically ensue after ART interruption.

Original languageEnglish (US)
Article numbere153046
JournalJCI Insight
Volume7
Issue number5
DOIs
StatePublished - Mar 8 2022
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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