RIG-I mediates the co-induction of tumor necrosis factor and type I interferon elicited by myxoma virus in primary human macrophages

Fuan Wang, Xiujuan Gao, John W. Barrett, Qing Shao, Eric Bartee, Mohamed R. Mohamed, Masmudur Rahman, Steve Werden, Timothy Irvine, Jingxin Cao, Gregory A. Dekaban, Grant McFadden

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

The sensing of pathogen infection and subsequent triggering of innate immunity are key to controlling zoonotic infections. Myxoma virus (MV) is a cytoplasmic DNA poxvirus that in nature infects only rabbits. Our previous studies have shown that MV infection of primary mouse cells is restricted by virus-induced type I interferon (IFN). However, little is known about the innate sensor(s) involved in activating signaling pathways leading to cellular defense responses in primary human immune cells. Here, we show that the complete restriction of MV infection in the primary human fibroblasts requires both tumor necrosis factor (TNF) and type I IFN. We also demonstrate that MV infection of primary human macrophages (pHMs) activates the cytoplasmic RNA sensor called retinoic acid inducible gene I (RIG-I), which coordinately induces the production of both TNF and type I IFN. Of note, RIG-I sensing of MV infection in pHMs initiates a sustained TNF induction through the sequential involvement of the downstream IFN-regulatory factors 3 and 7 (IRF3 and IRF7). Thus, RIG-I-mediated co-induction of TNF and type I IFN by virus-infected pHMs represents a novel innate defense mechanism to restrict viral infection in human cells. These results also reveal a new regulatory mechanism for TNF induction following viral infection.

Original languageEnglish (US)
Article numbere1000099
JournalPLoS Pathogens
Volume4
Issue number7
DOIs
StatePublished - Jul 2008

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Wang, F., Gao, X., Barrett, J. W., Shao, Q., Bartee, E., Mohamed, M. R., Rahman, M., Werden, S., Irvine, T., Cao, J., Dekaban, G. A., & McFadden, G. (2008). RIG-I mediates the co-induction of tumor necrosis factor and type I interferon elicited by myxoma virus in primary human macrophages. PLoS Pathogens, 4(7), [e1000099]. https://doi.org/10.1371/journal.ppat.1000099