Stage-specific ISG expression reveals functional convergence of type I and II IFNs in SIV infection

Abstract

AbstractInterferons play a major role in controlling viral infections including HIV/SIV infections. Persistent up-regulation of interferon-stimulated-genes (ISGs) is associated with chronic immune activation and progression in SIV/HIV infections, but the respective contribution of different IFNs is unclear. We analyzed the expression of annotated IFN-induced genes in SIV-infected macaques to decrypt the respective roles of type-I (α,β) and type-II (γ) IFNs. Both IFN types were induced in lymph nodes during early stage of primary infection. Induction of type-II IFN persisted during the chronic phase, in contrast to undetectable induction of type-I IFN. Interferome-based analysis of ISGs revealed that at both acute and chronic infection phases most differentially expressed ISGs were inducible by both type-I and type-II IFNs and displayed the highest increases, indicating strong convergence and synergy between type-I and type-II IFNs. The analysis of functional signatures of ISG expression revealed temporal changes in IFN expression patterns identifying phase-specific ISGs. These results suggest that IFN-γ strongly contribute to shape ISG upregulation in addition to type-I IFN and may contribute to progression.