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Sensors 2015, 15(10), 27160-27173; doi:10.3390/s151027160

Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV)

1
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan
2
Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan
Present Address: Department of Immunology, Graduate School of Medicine, Kumamoto University, Honjo, Chuoh-ku, Kumamoto 860-8556, Japan
*
Authors to whom correspondence should be addressed.
Academic Editor: Alexander Star
Received: 26 May 2015 / Revised: 10 October 2015 / Accepted: 19 October 2015 / Published: 23 October 2015
(This article belongs to the Section Biosensors)
View Full-Text   |   Download PDF [872 KB, uploaded 23 October 2015]   |  

Abstract

Hepatitis C virus (HCV) infects hepatocytes but not dendritic cells (DCs), but DCs effectively mature in response to HCV-infected hepatocytes. Using gene-disrupted mice and hydrodynamic injection strategy, we found the MAVS pathway to be crucial for induction of type III interferons (IFNs) in response to HCV in mouse. Human hepatocytes barely express TLR3 under non-infectious states, but frequently express it in HCV infection. Type I and III IFNs are induced upon stimulation with polyI:C, an analog of double-stranded (ds)RNA. Activation of TLR3 and the TICAM-1 pathway, followed by DC-mediated activation of cellular immunity, is augmented during exposure to viral RNA. Although type III IFNs are released from replication-competent human hepatocytes, DC-mediated CTL proliferation and NK cell activation hardly occur in response to the released type III IFNs. Yet, type I IFNs and HCV-infected hepatocytes can induce maturation of DCs in either human or mouse origin. In addition, mouse CD8+ DCs mature in response to HCV-infected hepatocytes unless the TLR3/TICAM-1 pathway is blocked. We found the exosomes containing HCV RNA in the supernatant of the HCV-infected hepatocytes act as a source of TLR3-mediated DC maturation. Here we summarize our view on the mechanism by which DCs mature to induce NK and CTL in a status of HCV infection. View Full-Text
Keywords: Hepatitis C virus (HCV); interferon (IFN)-lambda; dendritic cells (DCs); Toll-like receptor 3 (TLR3); natural killer (NK) cell; cytotoxic T lymphocyte (CTL) Hepatitis C virus (HCV); interferon (IFN)-lambda; dendritic cells (DCs); Toll-like receptor 3 (TLR3); natural killer (NK) cell; cytotoxic T lymphocyte (CTL)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Nakai, M.; Oshiumi, H.; Funami, K.; Okamoto, M.; Matsumoto, M.; Seya, T.; Sakamoto, N. Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV). Sensors 2015, 15, 27160-27173.

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