Stage-specific IFN-induced and IFN gene expression reveal convergence of type I and type II IFN and highlight their role in both acute and chronic stage of pathogenic SIV infection

PLoS One. 2018 Jan 11;13(1):e0190334. doi: 10.1371/journal.pone.0190334. eCollection 2018.

Abstract

Interferons (IFNs) 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 IFN genes and ISGs in tissues of SIV infected macaques to understand the respective roles of type I and type II IFNs. Both IFN types were induced in lymph nodes during early stage of primary infection and to some extent in rectal biopsies but not in PBMCs. Induction of Type II IFN expression persisted during the chronic phase, in contrast to undetectable induction of type I IFN expression. Global gene expression analysis with a major focus on 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Chronic Disease
  • Gene Expression*
  • Interferon Type I / genetics*
  • Interferon-gamma / genetics*
  • Macaca fascicularis
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / physiology
  • Transcriptome
  • Virus Replication

Substances

  • Interferon Type I
  • Interferon-gamma

Grants and funding

This work was supported by the Agence Nationale de Recherches sur le SIDA et les hépatites virales (www.anrs.fr). NE, SD and CPBP benefited from ANRS post-doctoral fellowships. This work was also supported by Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) through research project grant 11360 attributed to BV, by the agence Nationale de la Recherche (http://www.agence-nationale-recherche.fr) “Programme d’Investissements d’Avenir” (PIA) under Grant ANR-11-INBS-0008, that funds the Infectious Disease Models and Innovative Therapies (IDMIT, Fontenay-aux-Roses, France) infrastructure, and PIA grant ANR-10-EQPX-02-01 that funds the FlowCyTech facility (project investigator RLG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.