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

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-1? and TNF? remarkably reduced the host cell susceptibility to HBV infection. This effect was mediated by activation of the NF-?B signaling pathway. A cytidine deaminase, activation-induced cytidine deaminase (AID), was up-regulated by both IL-1? and TNF? 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-1?, and overexpression of AID antagonized HBV infection, suggesting that AID was one of the responsible factors for the anti-HBV activity of IL-1/TNF?. Although AID induced hypermutation of HBV DNA, this activity was dispensable for the anti-HBV activity. The antiviral effect of IL-1/TNF? was also observed on different HBV genotypes but not on hepatitis C virus. These results demonstrate that proinflammatory cytokines IL-1/TNF? trigger a novel antiviral mechanism involving AID to regulate host cell permissiveness to HBV infection.

SUBMITTER: Watashi K

PROVIDER: S-EPMC3814766 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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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).

Watashi Koichi K Liang Guoxin G Iwamoto Masashi M Marusawa Hiroyuki H Uchida Nanako N Daito Takuji T Kitamura Kouichi K Muramatsu Masamichi M Ohashi Hirofumi H Kiyohara Tomoko T Suzuki Ryosuke R Li Jisu J Tong Shuping S Tanaka Yasuhito Y Murata Kazumoto K Aizaki Hideki H Wakita Takaji T

The Journal of biological chemistry 20130911 44

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 sus ...[more]

PMID: 24025329

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Project description:Activation-induced cytidine deaminase (AID) is expressed in B cells within germinal centers and is critically involved in class switch recombination and somatic hypermutation of immunoglobulin loci. Functionally active AID can additionally be detected within ectopic follicular structures developed at sites of chronic inflammation. Furthermore, AID may target non-Ig genes in B- and non-B-cell background. Therefore, AID-associated effects are of increasing interest in disease areas such as allergy, inflammation, autoimmunity, and cancer.Pathway- or disease-relevant multigene signatures have attracted substantial attention for therapeutic target proposal, diagnostic tools, and monitoring of therapy response. To delineate the impact of AID in etiology of multifactorial diseases, we designed the AID-associated 25-gene signature. Chronic rhinosinusitis with nasal polyps was used as an inflammation-driven airway disease model; high levels of IgE have been previously shown to be present within polyp tissue. Expression levels of 16 genes were found to be modulated in polyps including AID, IgG and IgE mature transcripts which reflect AID activity; clustering algorithm revealed an AID-specific gene signature for the disease state with nasal polyp. Complementary, AID-positive ectopic lymphoid structures were detected within polyp tissues by in situ immunostaining. Our data demonstrate the class switch recombination and somatic hypermutation events likely taking place locally in the airways and in addition to the previously highlighted markers and/or targets as IL5 and IgE suggest novel candidate genes to be considered for treatment of nasal polyposis including among others IL13 and CD23. Thus, the algorithm presented herein including the multigene signature approach, analysis of co-regularities and creation of AID-associated functional network gives an integrated view of biological processes and might be further applied to assess role of altered AID expression in etiology of other diseases, in particular, aberrant immunity and cancer.

Dataset Information

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

Publications

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

Similar Datasets

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