Junín virus infection activates the type I interferon pathway in a RIG-I-dependent manner

Cheng Huang, Olga A. Kolokoltsova, Nadezdha E. Yun, Alexey V. Seregin, Allison L. Poussard, Aida G. Walker, Allan R. Brasier, Yingxin Zhao, Bing Tian, Juan Carlos de la Torre, Slobodan Paessler

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43 Scopus citations

Abstract

Junín virus (JUNV), an arenavirus, is the causative agent of Argentine hemorrhagic fever, an infectious human disease with 15-30% case fatality. The pathogenesis of AHF is still not well understood. Elevated levels of interferon and cytokines are reported in AHF patients, which might be correlated to the severity of the disease. However the innate immune response to JUNV infection has not been well evaluated. Previous studies have suggested that the virulent strain of JUNV does not induce IFN in human macrophages and monocytes, whereas the attenuated strain of JUNV was found to induce IFN response in murine macrophages via the TLR-2 signaling pathway. In this study, we investigated the interaction between JUNV and IFN pathway in human epithelial cells highly permissive to JUNV infection. We have determined the expression pattern of interferon-stimulated genes (ISGs) and IFN-β at both mRNA and protein levels during JUNV infection. Our results clearly indicate that JUNV infection activates the type I IFN response. STAT1 phosphorylation, a downstream marker of activation of IFN signaling pathway, was readily detected in JUNV infected IFN-competent cells. Our studies also demonstrated for the first time that RIG-I was required for IFN production during JUNV infection. IFN activation was detected during infection by either the virulent or attenuated vaccine strain of JUNV. Curiously, both virus strains were relatively insensitive to human IFN treatment. Our studies collectively indicated that JUNV infection could induce host type I IFN response and provided new insights into the interaction between JUNV and host innate immune system, which might be important in future studies on vaccine development and antiviral treatment.

Original languageEnglish (US)
Article numbere1659
JournalPLoS neglected tropical diseases
Volume6
Issue number5
DOIs
StatePublished - May 2012

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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    Huang, C., Kolokoltsova, O. A., Yun, N. E., Seregin, A. V., Poussard, A. L., Walker, A. G., Brasier, A. R., Zhao, Y., Tian, B., de la Torre, J. C., & Paessler, S. (2012). Junín virus infection activates the type I interferon pathway in a RIG-I-dependent manner. PLoS neglected tropical diseases, 6(5), [e1659]. https://doi.org/10.1371/journal.pntd.0001659