Junín virus infection activates the type I interferon pathway in a RIG-I-dependent manner.
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.
Galveston National Laboratory, Department of Pathology and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA.
Cheng
C
Huang
Olga A
OA
Kolokoltsova
Nadezdha E
NE
Yun
Alexey V
AV
Seregin
Allison L
AL
Poussard
Aida G
AG
Walker
Allan R
AR
Brasier
Yingxin
Y
Zhao
Bing
B
Tian
Juan Carlos
JC
de la Torre
Slobodan
S
Paessler
D001117:Arenaviridae Infections / Q000276:immunology*; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology*; D020869:Gene Expression Profiling; D006478:Hemorrhagic Fever, American / Q000821:virology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D018051:Junin virus / Q000276:immunology* / Q000472:pathogenicity; D010766:Phosphorylation; D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor / Q000378:metabolism
D007370:Interferon Type I; D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases