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Interleukin-1 and tumor necrosis factor-α trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID).

Authors
  • Watashi, Koichi
  • Liang, Guoxin
  • Iwamoto, Masashi
  • Marusawa, Hiroyuki
  • Uchida, Nanako
  • Daito, Takuji
  • Kitamura, Kouichi
  • Muramatsu, Masamichi
  • Ohashi, Hirofumi
  • Kiyohara, Tomoko
  • Suzuki, Ryosuke
  • Li, Jisu
  • Tong, Shuping
  • Tanaka, Yasuhito
  • Murata, Kazumoto
  • Aizaki, Hideki
  • Wakita, Takaji
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Nov 01, 2013
Volume
288
Issue
44
Pages
31715–31727
Identifiers
DOI: 10.1074/jbc.M113.501122
PMID: 24025329
Source
Medline
Keywords
License
Unknown

Abstract

Virus infection is restricted by intracellular immune responses in host cells, and this is typically modulated by stimulation of cytokines. The cytokines and host factors that determine the host cell restriction against hepatitis B virus (HBV) infection are not well understood. We screened 36 cytokines and chemokines to determine which were able to reduce the susceptibility of HepaRG cells to HBV infection. Here, we found that pretreatment with IL-1β and TNFα remarkably reduced the host cell susceptibility to HBV infection. This effect was mediated by activation of the NF-κB signaling pathway. A cytidine deaminase, activation-induced cytidine deaminase (AID), was up-regulated by both IL-1β and TNFα in a variety of hepatocyte cell lines and primary human hepatocytes. Another deaminase APOBEC3G was not induced by these proinflammatory cytokines. Knockdown of AID expression impaired the anti-HBV effect of IL-1β, and overexpression of AID antagonized HBV infection, suggesting that AID was one of the responsible factors for the anti-HBV activity of IL-1/TNFα. Although AID induced hypermutation of HBV DNA, this activity was dispensable for the anti-HBV activity. The antiviral effect of IL-1/TNFα was also observed on different HBV genotypes but not on hepatitis C virus. These results demonstrate that proinflammatory cytokines IL-1/TNFα trigger a novel antiviral mechanism involving AID to regulate host cell permissiveness to HBV infection.

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