Enhanced RIG-I expression is mediated by interferon regulatory factor-2 in peripheral blood B cells from hepatitis C virus-infected patients.
Chronic hepatitis C patients carry the risk of developing into B-cell non-Hodgkin's lymphoma (B-NHL). To clarify the mechanisms underlying this association, we first investigated the molecular markers of B cells from hepatitis C virus (HCV)-infected patients. CD19-positive cells were isolated as B cells from the peripheral blood mononuclear cells of patients infected with the hepatitis C virus and IFN-related gene expression was analyzed. We found that RIG-I and IRF-2 expression were up-regulated in CD19-positive cells from the infected patients. In vitro luciferase reporter analysis using human cell lines indicated that IRF-2 activates the human RIG-I promoter. IRF-2 expression levels were enhanced by HCV cDNA transfection in Huh7 cells. In addition, we observed much less induction in the interferon stimulated gene 15 (ISG15) after Sendai virus (SenV) stimulation of CD19-positive cells from infected patients versus healthy controls, thereby suggesting an impairment of RIG-I downstream signaling in HCV-infected patients. Hence, we found that the failure of the anti-viral response with enhanced IRF-2 oncogenic protein expression in blood B cells from HCV-infected patients. Our results provide important information to better understand the role of IRFs in the cause of HCV chronic infection.
Masumi
Atsuko
A
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, 4-7-1, Gakuen Musashimurayama-shi, Tokyo 208-0011, Japan. amasumi@nih.go.jp
Ito
Masahiko
M
Mochida
Keiko
K
Hamaguchi
Isao
I
Mizukami
Takuo
T
Momose
Haruka
H
Kuramitsu
Madoka
M
Tsuruhara
Momoka
M
Takizawa
Kazuya
K
Kato
Atsushi
A
Yamaguchi
Kazunari
K
D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050836:Interferon Regulatory Factor-2 / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000821:virology; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic; D015533:Transcriptional Activation
D018941:Antigens, CD19; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases