Genomic Analysis of the Host Response to Hepatitis C Virus Infection
We have examined the progression of hepatitis C virus (HCV) infections by gene expression analysis of liver biopsies in acutely infected chimpanzees that developed persistent infection, transient viral clearance, or sustained clearance. Both common responses and outcome-specific changes in expressio...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2002-11, Vol.99 (24), p.15669-15674 |
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| container_issue | 24 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 99 |
| creator | Su, Andrew I. Pezacki, John P. Wodicka, Lisa Brideau, Amy D. Supekova, Lubica Thimme, Robert Wieland, Stefan Bukh, Jens Purcell, Robert H. Schultz, Peter G. Chisari, Francis V. |
| description | We have examined the progression of hepatitis C virus (HCV) infections by gene expression analysis of liver biopsies in acutely infected chimpanzees that developed persistent infection, transient viral clearance, or sustained clearance. Both common responses and outcome-specific changes in expression were observed. All chimpanzees showed gene expression patterns consistent with an IFN-α response that correlated with the magnitude and duration of infection. Transient and sustained viral clearance were uniquely associated with induction of IFN-γ-induced genes and other genes involved in antigen processing and presentation and the adaptive immune response. During the early stages of infection, host genes involved in lipid metabolism were also differentially regulated. We also show that drugs that affect these biosynthetic pathways can regulate HCV replication in HCV replicon systems. Our results reveal genome-wide transcriptional changes that reflect the establishment, spread, and control of infection, and they reveal potentially unique antiviral programs associated with clearance of HCV infection. |
| doi_str_mv | 10.1073/pnas.202608199 |
| format | Article |
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Both common responses and outcome-specific changes in expression were observed. All chimpanzees showed gene expression patterns consistent with an IFN-α response that correlated with the magnitude and duration of infection. Transient and sustained viral clearance were uniquely associated with induction of IFN-γ-induced genes and other genes involved in antigen processing and presentation and the adaptive immune response. During the early stages of infection, host genes involved in lipid metabolism were also differentially regulated. We also show that drugs that affect these biosynthetic pathways can regulate HCV replication in HCV replicon systems. Our results reveal genome-wide transcriptional changes that reflect the establishment, spread, and control of infection, and they reveal potentially unique antiviral programs associated with clearance of HCV infection.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.202608199</identifier><identifier>PMID: 12441396</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Antigen Presentation ; Biological Sciences ; Cell lines ; Fatty Acids - metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Genes ; Genes, Reporter ; Genomics ; Hepacivirus - drug effects ; Hepacivirus - genetics ; Hepacivirus - physiology ; Hepatitis ; Hepatitis C ; Hepatitis C - genetics ; Hepatitis C - immunology ; Hepatitis C - metabolism ; Infections ; Interferons - biosynthesis ; Lipid Metabolism ; Liver ; Microbiology ; Pan troglodytes ; Replicon ; RNA ; T lymphocytes ; Transcription, Genetic ; Transfection ; Viremia - genetics ; Viremia - immunology ; Virus Replication - drug effects ; Viruses</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2002-11, Vol.99 (24), p.15669-15674</ispartof><rights>Copyright 1993-2002 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Nov 26, 2002</rights><rights>Copyright © 2002, The National Academy of Sciences</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c652t-6b087ecfb20216461b04cc599145d8cd4bd9a7163ba2c5b2a06593b9ceb9bcf83</citedby><cites>FETCH-LOGICAL-c652t-6b087ecfb20216461b04cc599145d8cd4bd9a7163ba2c5b2a06593b9ceb9bcf83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/99/24.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3073830$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3073830$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,728,781,785,804,886,27928,27929,53795,53797,58021,58254</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12441396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Su, Andrew I.</creatorcontrib><creatorcontrib>Pezacki, John P.</creatorcontrib><creatorcontrib>Wodicka, Lisa</creatorcontrib><creatorcontrib>Brideau, Amy D.</creatorcontrib><creatorcontrib>Supekova, Lubica</creatorcontrib><creatorcontrib>Thimme, Robert</creatorcontrib><creatorcontrib>Wieland, Stefan</creatorcontrib><creatorcontrib>Bukh, Jens</creatorcontrib><creatorcontrib>Purcell, Robert H.</creatorcontrib><creatorcontrib>Schultz, Peter G.</creatorcontrib><creatorcontrib>Chisari, Francis V.</creatorcontrib><title>Genomic Analysis of the Host Response to Hepatitis C Virus Infection</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We have examined the progression of hepatitis C virus (HCV) infections by gene expression analysis of liver biopsies in acutely infected chimpanzees that developed persistent infection, transient viral clearance, or sustained clearance. Both common responses and outcome-specific changes in expression were observed. All chimpanzees showed gene expression patterns consistent with an IFN-α response that correlated with the magnitude and duration of infection. Transient and sustained viral clearance were uniquely associated with induction of IFN-γ-induced genes and other genes involved in antigen processing and presentation and the adaptive immune response. During the early stages of infection, host genes involved in lipid metabolism were also differentially regulated. We also show that drugs that affect these biosynthetic pathways can regulate HCV replication in HCV replicon systems. Our results reveal genome-wide transcriptional changes that reflect the establishment, spread, and control of infection, and they reveal potentially unique antiviral programs associated with clearance of HCV infection.</description><subject>Animals</subject><subject>Antigen Presentation</subject><subject>Biological Sciences</subject><subject>Cell lines</subject><subject>Fatty Acids - metabolism</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genes, Reporter</subject><subject>Genomics</subject><subject>Hepacivirus - drug effects</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - physiology</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C - genetics</subject><subject>Hepatitis C - immunology</subject><subject>Hepatitis C - metabolism</subject><subject>Infections</subject><subject>Interferons - biosynthesis</subject><subject>Lipid Metabolism</subject><subject>Liver</subject><subject>Microbiology</subject><subject>Pan troglodytes</subject><subject>Replicon</subject><subject>RNA</subject><subject>T lymphocytes</subject><subject>Transcription, Genetic</subject><subject>Transfection</subject><subject>Viremia - genetics</subject><subject>Viremia - immunology</subject><subject>Virus Replication - drug effects</subject><subject>Viruses</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0TuPEzEUBWALgdiw0FIhsCgQzYTrx_hRUKwCbFZaCQkBrWU7HnaiyXiwPYj99zhKCI8CKhf-ztW1D0KPCSwJSPZqGm1eUqACFNH6DloQ0KQRXMNdtACgslGc8jP0IOctAOhWwX10RijnhGmxQG8uwxh3vccXox1uc59x7HC5CXgdc8EfQp7imAMuEa_DZEtfqljhz32aM74au-BLH8eH6F5nhxweHc9z9Ond24-rdXP9_vJqdXHdeNHS0ggHSgbfubovEVwQB9z7VmvC243yG-422koimLPUt45aEK1mTvvgtPOdYufo9WHuNLtd2PgwlmQHM6V-Z9OtibY3f96M_Y35Er8ZwqSUvOZfHPMpfp1DLmbXZx-GwY4hztlIKqkCIv8LiRJQZ9IKn_8Ft3FO9SuzoVVo1lKoaHlAPsWcU-hOGxMw-xbNvkVzarEGnv7-zl_8WFsFz45gH_x5rbWh3JBWiP2Il_8WppuHoYTvpdInB7rNJaaTZXUxxYD9APadudE</recordid><startdate>20021126</startdate><enddate>20021126</enddate><creator>Su, Andrew I.</creator><creator>Pezacki, John P.</creator><creator>Wodicka, Lisa</creator><creator>Brideau, Amy D.</creator><creator>Supekova, Lubica</creator><creator>Thimme, Robert</creator><creator>Wieland, Stefan</creator><creator>Bukh, Jens</creator><creator>Purcell, Robert H.</creator><creator>Schultz, Peter G.</creator><creator>Chisari, Francis V.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20021126</creationdate><title>Genomic Analysis of the Host Response to Hepatitis C Virus Infection</title><author>Su, Andrew I. ; 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Both common responses and outcome-specific changes in expression were observed. All chimpanzees showed gene expression patterns consistent with an IFN-α response that correlated with the magnitude and duration of infection. Transient and sustained viral clearance were uniquely associated with induction of IFN-γ-induced genes and other genes involved in antigen processing and presentation and the adaptive immune response. During the early stages of infection, host genes involved in lipid metabolism were also differentially regulated. We also show that drugs that affect these biosynthetic pathways can regulate HCV replication in HCV replicon systems. Our results reveal genome-wide transcriptional changes that reflect the establishment, spread, and control of infection, and they reveal potentially unique antiviral programs associated with clearance of HCV infection.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>12441396</pmid><doi>10.1073/pnas.202608199</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigen Presentation Biological Sciences Cell lines Fatty Acids - metabolism Gene Expression Profiling Gene Expression Regulation Genes Genes, Reporter Genomics Hepacivirus - drug effects Hepacivirus - genetics Hepacivirus - physiology Hepatitis Hepatitis C Hepatitis C - genetics Hepatitis C - immunology Hepatitis C - metabolism Infections Interferons - biosynthesis Lipid Metabolism Liver Microbiology Pan troglodytes Replicon RNA T lymphocytes Transcription, Genetic Transfection Viremia - genetics Viremia - immunology Virus Replication - drug effects Viruses |
| title | Genomic Analysis of the Host Response to Hepatitis C Virus Infection |
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