Interleukin-1 and Tumor Necrosis Factor-α Trigger Restriction of Hepatitis B Virus Infection via a Cytidine Deaminase Activation-induced Cytidine Deaminase (AID)
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 cytoki...
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| Veröffentlicht in: | The Journal of biological chemistry 2013-11, Vol.288 (44), p.31715-31727 |
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| creator | 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 |
| description | 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.
Background: Cytokines and host factors triggering innate immunity against hepatitis B virus (HBV) are not well understood.
Results: IL-1 and TNFα induced cytidine deaminase AID, an anti-HBV host factor, and reduced HBV infection into hepatocytes.
Conclusion: IL-1/TNFα reduced host susceptibility to HBV infection through AID up-regulation.
Significance: Proinflammatory cytokines modulate HBV infection through a novel innate immune pathway involving AID. |
| doi_str_mv | 10.1074/jbc.M113.501122 |
| format | Article |
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Background: Cytokines and host factors triggering innate immunity against hepatitis B virus (HBV) are not well understood.
Results: IL-1 and TNFα induced cytidine deaminase AID, an anti-HBV host factor, and reduced HBV infection into hepatocytes.
Conclusion: IL-1/TNFα reduced host susceptibility to HBV infection through AID up-regulation.
Significance: Proinflammatory cytokines modulate HBV infection through a novel innate immune pathway involving AID.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M113.501122</identifier><identifier>PMID: 24025329</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>AID ; APOBEC3G ; Cytidine Deaminase - biosynthesis ; Cytidine Deaminase - genetics ; Cytidine Deaminase - immunology ; Deaminase ; DNA, Viral - biosynthesis ; DNA, Viral - genetics ; DNA, Viral - immunology ; Gene Expression Regulation, Enzymologic ; HBV ; Hep G2 Cells ; Hepacivirus - genetics ; Hepacivirus - immunology ; Hepacivirus - metabolism ; HepaRG ; Hepatitis B - genetics ; Hepatitis B - immunology ; Hepatitis B - metabolism ; Hepatitis B virus ; Hepatitis B virus - genetics ; Hepatitis B virus - immunology ; Hepatitis B virus - metabolism ; Hepatitis C virus ; Humans ; Innate Immunity ; Interferon ; Interleukin ; Interleukin-1beta - genetics ; Interleukin-1beta - immunology ; Interleukin-1beta - metabolism ; Microbiology ; Mutation ; Tumor Necrosis Factor (TNF) ; Tumor Necrosis Factor-alpha - genetics ; Tumor Necrosis Factor-alpha - immunology ; Tumor Necrosis Factor-alpha - metabolism ; Up-Regulation - genetics ; Virus</subject><ispartof>The Journal of biological chemistry, 2013-11, Vol.288 (44), p.31715-31727</ispartof><rights>2013 © 2013 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2013 by The American Society for Biochemistry and Molecular Biology, Inc. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4352-1b74b25eb3b5b67924c655eacee07795bf024c9c2466fee845adf6885c1664203</citedby><cites>FETCH-LOGICAL-c4352-1b74b25eb3b5b67924c655eacee07795bf024c9c2466fee845adf6885c1664203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814766/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814766/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24025329$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Watashi, Koichi</creatorcontrib><creatorcontrib>Liang, Guoxin</creatorcontrib><creatorcontrib>Iwamoto, Masashi</creatorcontrib><creatorcontrib>Marusawa, Hiroyuki</creatorcontrib><creatorcontrib>Uchida, Nanako</creatorcontrib><creatorcontrib>Daito, Takuji</creatorcontrib><creatorcontrib>Kitamura, Kouichi</creatorcontrib><creatorcontrib>Muramatsu, Masamichi</creatorcontrib><creatorcontrib>Ohashi, Hirofumi</creatorcontrib><creatorcontrib>Kiyohara, Tomoko</creatorcontrib><creatorcontrib>Suzuki, Ryosuke</creatorcontrib><creatorcontrib>Li, Jisu</creatorcontrib><creatorcontrib>Tong, Shuping</creatorcontrib><creatorcontrib>Tanaka, Yasuhito</creatorcontrib><creatorcontrib>Murata, Kazumoto</creatorcontrib><creatorcontrib>Aizaki, Hideki</creatorcontrib><creatorcontrib>Wakita, Takaji</creatorcontrib><title>Interleukin-1 and Tumor Necrosis Factor-α Trigger Restriction of Hepatitis B Virus Infection via a Cytidine Deaminase Activation-induced Cytidine Deaminase (AID)</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>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.
Background: Cytokines and host factors triggering innate immunity against hepatitis B virus (HBV) are not well understood.
Results: IL-1 and TNFα induced cytidine deaminase AID, an anti-HBV host factor, and reduced HBV infection into hepatocytes.
Conclusion: IL-1/TNFα reduced host susceptibility to HBV infection through AID up-regulation.
Significance: Proinflammatory cytokines modulate HBV infection through a novel innate immune pathway involving AID.</description><subject>AID</subject><subject>APOBEC3G</subject><subject>Cytidine Deaminase - biosynthesis</subject><subject>Cytidine Deaminase - genetics</subject><subject>Cytidine Deaminase - immunology</subject><subject>Deaminase</subject><subject>DNA, Viral - biosynthesis</subject><subject>DNA, Viral - genetics</subject><subject>DNA, Viral - immunology</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>HBV</subject><subject>Hep G2 Cells</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - immunology</subject><subject>Hepacivirus - metabolism</subject><subject>HepaRG</subject><subject>Hepatitis B - genetics</subject><subject>Hepatitis B - immunology</subject><subject>Hepatitis B - metabolism</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B virus - immunology</subject><subject>Hepatitis B virus - metabolism</subject><subject>Hepatitis C virus</subject><subject>Humans</subject><subject>Innate Immunity</subject><subject>Interferon</subject><subject>Interleukin</subject><subject>Interleukin-1beta - genetics</subject><subject>Interleukin-1beta - immunology</subject><subject>Interleukin-1beta - metabolism</subject><subject>Microbiology</subject><subject>Mutation</subject><subject>Tumor Necrosis Factor (TNF)</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Up-Regulation - genetics</subject><subject>Virus</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNktFqFDEUhoNY7Fq99k5yWS9mm2SSzMyNsG6tXagKsop3IZM5s546m1mTmYW-jm_gi_hMZpm2KCgYAoGcLz8n5_8JecbZnLNCnl3Xbv6W83yuGOdCPCAzzso8yxX__JDMGBM8q4Qqj8njGK9ZWrLij8ixkEyoXFQz8n3lBwgdjF_RZ5xa39D1uO0DfQcu9BEjvbBu6EP28wddB9xsINAPEIeAbsDe076ll7CzAw4JfUU_YRgjXfkWpvIeLbV0eTNggx7oOdgtehuBLlJ9bw9Mhr4ZHTR_o04Xq_MXT8hRa7sIT2_PE_Lx4vV6eZldvX-zWi6uMidzJTJeF7IWCuq8VrUuKiGdVgqsA2BFUam6ZemqckJq3QKUUtmm1WWpHNdaCpafkJeT7m6st9A48EOwndkF3NpwY3qL5s-Kxy9m0-9NXnJZaJ0ETm8FQv9tTEMyW4wOus566MdouNRSMaV09R-orESRp53Qswk9-BEDtPcdcWYOITApBOYQAjOFIL14_vtH7vk71xNQTQCkce4RgokOwScTMCTjTNPjP8V_ATC0wzY</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Watashi, Koichi</creator><creator>Liang, Guoxin</creator><creator>Iwamoto, Masashi</creator><creator>Marusawa, Hiroyuki</creator><creator>Uchida, Nanako</creator><creator>Daito, Takuji</creator><creator>Kitamura, Kouichi</creator><creator>Muramatsu, Masamichi</creator><creator>Ohashi, Hirofumi</creator><creator>Kiyohara, Tomoko</creator><creator>Suzuki, Ryosuke</creator><creator>Li, Jisu</creator><creator>Tong, Shuping</creator><creator>Tanaka, Yasuhito</creator><creator>Murata, Kazumoto</creator><creator>Aizaki, Hideki</creator><creator>Wakita, Takaji</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20131101</creationdate><title>Interleukin-1 and Tumor Necrosis Factor-α Trigger Restriction of Hepatitis B Virus Infection via a Cytidine Deaminase Activation-induced Cytidine Deaminase (AID)</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4352-1b74b25eb3b5b67924c655eacee07795bf024c9c2466fee845adf6885c1664203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>AID</topic><topic>APOBEC3G</topic><topic>Cytidine Deaminase - biosynthesis</topic><topic>Cytidine Deaminase - genetics</topic><topic>Cytidine Deaminase - immunology</topic><topic>Deaminase</topic><topic>DNA, Viral - biosynthesis</topic><topic>DNA, Viral - genetics</topic><topic>DNA, Viral - immunology</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>HBV</topic><topic>Hep G2 Cells</topic><topic>Hepacivirus - genetics</topic><topic>Hepacivirus - immunology</topic><topic>Hepacivirus - metabolism</topic><topic>HepaRG</topic><topic>Hepatitis B - genetics</topic><topic>Hepatitis B - immunology</topic><topic>Hepatitis B - metabolism</topic><topic>Hepatitis B virus</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B virus - immunology</topic><topic>Hepatitis B virus - metabolism</topic><topic>Hepatitis C virus</topic><topic>Humans</topic><topic>Innate Immunity</topic><topic>Interferon</topic><topic>Interleukin</topic><topic>Interleukin-1beta - genetics</topic><topic>Interleukin-1beta - immunology</topic><topic>Interleukin-1beta - metabolism</topic><topic>Microbiology</topic><topic>Mutation</topic><topic>Tumor Necrosis Factor (TNF)</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumor Necrosis Factor-alpha - immunology</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Up-Regulation - genetics</topic><topic>Virus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Watashi, Koichi</creatorcontrib><creatorcontrib>Liang, Guoxin</creatorcontrib><creatorcontrib>Iwamoto, Masashi</creatorcontrib><creatorcontrib>Marusawa, Hiroyuki</creatorcontrib><creatorcontrib>Uchida, Nanako</creatorcontrib><creatorcontrib>Daito, Takuji</creatorcontrib><creatorcontrib>Kitamura, Kouichi</creatorcontrib><creatorcontrib>Muramatsu, Masamichi</creatorcontrib><creatorcontrib>Ohashi, Hirofumi</creatorcontrib><creatorcontrib>Kiyohara, Tomoko</creatorcontrib><creatorcontrib>Suzuki, Ryosuke</creatorcontrib><creatorcontrib>Li, Jisu</creatorcontrib><creatorcontrib>Tong, Shuping</creatorcontrib><creatorcontrib>Tanaka, Yasuhito</creatorcontrib><creatorcontrib>Murata, Kazumoto</creatorcontrib><creatorcontrib>Aizaki, Hideki</creatorcontrib><creatorcontrib>Wakita, Takaji</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Watashi, Koichi</au><au>Liang, Guoxin</au><au>Iwamoto, Masashi</au><au>Marusawa, Hiroyuki</au><au>Uchida, Nanako</au><au>Daito, Takuji</au><au>Kitamura, Kouichi</au><au>Muramatsu, Masamichi</au><au>Ohashi, Hirofumi</au><au>Kiyohara, Tomoko</au><au>Suzuki, Ryosuke</au><au>Li, Jisu</au><au>Tong, Shuping</au><au>Tanaka, Yasuhito</au><au>Murata, Kazumoto</au><au>Aizaki, Hideki</au><au>Wakita, Takaji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-1 and Tumor Necrosis Factor-α Trigger Restriction of Hepatitis B Virus Infection via a Cytidine Deaminase Activation-induced Cytidine Deaminase (AID)</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>288</volume><issue>44</issue><spage>31715</spage><epage>31727</epage><pages>31715-31727</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><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.
Background: Cytokines and host factors triggering innate immunity against hepatitis B virus (HBV) are not well understood.
Results: IL-1 and TNFα induced cytidine deaminase AID, an anti-HBV host factor, and reduced HBV infection into hepatocytes.
Conclusion: IL-1/TNFα reduced host susceptibility to HBV infection through AID up-regulation.
Significance: Proinflammatory cytokines modulate HBV infection through a novel innate immune pathway involving AID.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24025329</pmid><doi>10.1074/jbc.M113.501122</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 2013-11, Vol.288 (44), p.31715-31727 |
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| subjects | AID APOBEC3G Cytidine Deaminase - biosynthesis Cytidine Deaminase - genetics Cytidine Deaminase - immunology Deaminase DNA, Viral - biosynthesis DNA, Viral - genetics DNA, Viral - immunology Gene Expression Regulation, Enzymologic HBV Hep G2 Cells Hepacivirus - genetics Hepacivirus - immunology Hepacivirus - metabolism HepaRG Hepatitis B - genetics Hepatitis B - immunology Hepatitis B - metabolism Hepatitis B virus Hepatitis B virus - genetics Hepatitis B virus - immunology Hepatitis B virus - metabolism Hepatitis C virus Humans Innate Immunity Interferon Interleukin Interleukin-1beta - genetics Interleukin-1beta - immunology Interleukin-1beta - metabolism Microbiology Mutation Tumor Necrosis Factor (TNF) Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - immunology Tumor Necrosis Factor-alpha - metabolism Up-Regulation - genetics Virus |
| title | Interleukin-1 and Tumor Necrosis Factor-α Trigger Restriction of Hepatitis B Virus Infection via a Cytidine Deaminase Activation-induced Cytidine Deaminase (AID) |
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