DC Field | Value | Language |
---|---|---|
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.contributor.author | Protzer, U | ko |
dc.contributor.author | Untergasser, A | ko |
dc.contributor.author | Feinstone, SM | ko |
dc.contributor.author | Rice, CM | ko |
dc.contributor.author | Hasselschwert, D | ko |
dc.contributor.author | Rehermann, B | ko |
dc.date.accessioned | 2013-03-08T12:16:10Z | - |
dc.date.available | 2013-03-08T12:16:10Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2005-11 | - |
dc.identifier.citation | JOURNAL OF VIROLOGY, v.79, no.21, pp.13412 - 13420 | - |
dc.identifier.issn | 0022-538X | - |
dc.identifier.uri | http://hdl.handle.net/10203/92978 | - |
dc.description.abstract | Gamma interferon (IFN-gamma) has been shown to inhibit replication of subgenomic and genomic hepatitis C virus (HCV) RNAs in vitro and to noncytolytically suppress hepatitis B virus (HBV) replication in vivo. IFN-gamma is also known for its immunomodulatory effects and as a marker of a successful cellular immune response to HCV. Therapeutic expression of IFN-gamma in the liver may therefore facilitate resolution of chronic hepatitis C, an infection that is rarely resolved spontaneously. To analyze immunomodullatory and antiviral effects of liver-specific IFN-gamma expression in vivo, we intravenously injected two persistently HCV-infected chimpanzees twice with a recombinant, replication-deficient HBV vector and subsequently with a recombinant adenoviral vector. These vectors expressed human IFN-gamma under control of HBV- and liver-specific promoters, respectively. Gene transfer resulted in a transient increase of intrahepatic IFN-gamma mRNA, without increase in serum alanine aminotransferase levels. Ex vivo analysis of peripheral blood lymphocytes demonstrated enhanced CD16 expression on T cells and upregulation of the liver-homing marker CXCR3. Moreover, an increased frequency of HCV-specific T cells was detected ex vivo in the peripheral blood and in vitro in liver biopsy-derived, antigen-nonspecifically expanded T-cell lines. None of these immunologic effects were observed in the third chimpanzee injected with an HBV control vector. Despite these immunologic effects of the experimental vector, however, IFN-gamma gene transfer did not result in a significant and long-lasting decrease of HCV titers. In conclusion, liver-directed IFN-gamma gene delivery resulted in HCV-specific and nonspecific activation of cellular immune responses but did not result in effective control of HCV replication. | - |
dc.language | English | - |
dc.publisher | AMER SOC MICROBIOLOGY | - |
dc.subject | VIRUS-INFECTION | - |
dc.subject | IMMUNE-RESPONSES | - |
dc.subject | VIRAL CLEARANCE | - |
dc.subject | PLUS RIBAVIRIN | - |
dc.subject | T-CELLS | - |
dc.subject | EXPRESSION | - |
dc.subject | REPLICATION | - |
dc.subject | PERSISTENCE | - |
dc.subject | LYMPHOCYTES | - |
dc.subject | CHIMPANZEES | - |
dc.title | Liver-directed gamma interferon gene delivery in chronic hepatitis C | - |
dc.type | Article | - |
dc.identifier.wosid | 000232666300020 | - |
dc.identifier.scopusid | 2-s2.0-27144480649 | - |
dc.type.rims | ART | - |
dc.citation.volume | 79 | - |
dc.citation.issue | 21 | - |
dc.citation.beginningpage | 13412 | - |
dc.citation.endingpage | 13420 | - |
dc.citation.publicationname | JOURNAL OF VIROLOGY | - |
dc.identifier.doi | 10.1128/JVI.79.21.13412-13420.2005 | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Protzer, U | - |
dc.contributor.nonIdAuthor | Untergasser, A | - |
dc.contributor.nonIdAuthor | Feinstone, SM | - |
dc.contributor.nonIdAuthor | Rice, CM | - |
dc.contributor.nonIdAuthor | Hasselschwert, D | - |
dc.contributor.nonIdAuthor | Rehermann, B | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | VIRUS-INFECTION | - |
dc.subject.keywordPlus | IMMUNE-RESPONSES | - |
dc.subject.keywordPlus | VIRAL CLEARANCE | - |
dc.subject.keywordPlus | PLUS RIBAVIRIN | - |
dc.subject.keywordPlus | T-CELLS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | REPLICATION | - |
dc.subject.keywordPlus | PERSISTENCE | - |
dc.subject.keywordPlus | LYMPHOCYTES | - |
dc.subject.keywordPlus | CHIMPANZEES | - |
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