Hepatitis C virus replication in stably transfected HepG2 cells promotes hepatocellular growth and tumorigenesis
HepG2 cells stably transfected with a full‐length, infectious hepatitis C virus (HCV) cDNA demonstrated consistent replication of HCV for more than 3 years. Intracellular minus strand HCV RNA was present. Minus strand synthesis was NS5B dependent, and was sensitive to interferon alpha (IFNα) treatme...
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Veröffentlicht in: | Journal of cellular physiology 2004-12, Vol.201 (3), p.447-458 |
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container_title | Journal of cellular physiology |
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creator | Sun, Bill S. Pan, Jingbo Clayton, Marcy M. Liu, Jie Yan, Xiaoping Matskevich, Alexey A. Strayer, David S. Gerber, Michael Feitelson, Mark A. |
description | HepG2 cells stably transfected with a full‐length, infectious hepatitis C virus (HCV) cDNA demonstrated consistent replication of HCV for more than 3 years. Intracellular minus strand HCV RNA was present. Minus strand synthesis was NS5B dependent, and was sensitive to interferon alpha (IFNα) treatment. NS5B and HCV core protein were detectable. HCV stimulated HepG2 cell growth and survival in culture, in soft agar, and accelerated tumor growth in SCID mice. These mice became HCV RNA positive in blood, where the virus was also sensitive to IFNα. The RNA banded at the density of HCV, and was resistant to RNase prior to extraction. Hence, HCV stably replicates in HepG2 cells, stimulates hepatocellular growth and tumorigenesis, and is susceptible to IFNα both in vitro and in vivo. © 2004 Wiley‐Liss, Inc. |
doi_str_mv | 10.1002/jcp.20083 |
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Intracellular minus strand HCV RNA was present. Minus strand synthesis was NS5B dependent, and was sensitive to interferon alpha (IFNα) treatment. NS5B and HCV core protein were detectable. HCV stimulated HepG2 cell growth and survival in culture, in soft agar, and accelerated tumor growth in SCID mice. These mice became HCV RNA positive in blood, where the virus was also sensitive to IFNα. The RNA banded at the density of HCV, and was resistant to RNase prior to extraction. Hence, HCV stably replicates in HepG2 cells, stimulates hepatocellular growth and tumorigenesis, and is susceptible to IFNα both in vitro and in vivo. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.20083</identifier><identifier>PMID: 15389552</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic ; Gene Expression Regulation, Viral ; Hepacivirus - drug effects ; Hepacivirus - genetics ; Hepacivirus - physiology ; Hepatocytes - metabolism ; Hepatocytes - pathology ; Hepatocytes - virology ; Humans ; Interferon-alpha - pharmacology ; Mice ; Mice, SCID ; RNA Viruses - genetics ; RNA Viruses - isolation & purification ; Transfection ; Viral Core Proteins - metabolism ; Viral Nonstructural Proteins - metabolism ; Virus Replication</subject><ispartof>Journal of cellular physiology, 2004-12, Vol.201 (3), p.447-458</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4253-98593f7be65a94f29fd78a003ea00b31f80b7b27a58497db3fa19f597e4d76313</citedby><cites>FETCH-LOGICAL-c4253-98593f7be65a94f29fd78a003ea00b31f80b7b27a58497db3fa19f597e4d76313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.20083$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.20083$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15389552$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Bill S.</creatorcontrib><creatorcontrib>Pan, Jingbo</creatorcontrib><creatorcontrib>Clayton, Marcy M.</creatorcontrib><creatorcontrib>Liu, Jie</creatorcontrib><creatorcontrib>Yan, Xiaoping</creatorcontrib><creatorcontrib>Matskevich, Alexey A.</creatorcontrib><creatorcontrib>Strayer, David S.</creatorcontrib><creatorcontrib>Gerber, Michael</creatorcontrib><creatorcontrib>Feitelson, Mark A.</creatorcontrib><title>Hepatitis C virus replication in stably transfected HepG2 cells promotes hepatocellular growth and tumorigenesis</title><title>Journal of cellular physiology</title><addtitle>J. Cell. Physiol</addtitle><description>HepG2 cells stably transfected with a full‐length, infectious hepatitis C virus (HCV) cDNA demonstrated consistent replication of HCV for more than 3 years. Intracellular minus strand HCV RNA was present. Minus strand synthesis was NS5B dependent, and was sensitive to interferon alpha (IFNα) treatment. NS5B and HCV core protein were detectable. HCV stimulated HepG2 cell growth and survival in culture, in soft agar, and accelerated tumor growth in SCID mice. These mice became HCV RNA positive in blood, where the virus was also sensitive to IFNα. The RNA banded at the density of HCV, and was resistant to RNase prior to extraction. Hence, HCV stably replicates in HepG2 cells, stimulates hepatocellular growth and tumorigenesis, and is susceptible to IFNα both in vitro and in vivo. © 2004 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Transformation, Neoplastic</subject><subject>Gene Expression Regulation, Viral</subject><subject>Hepacivirus - drug effects</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - physiology</subject><subject>Hepatocytes - metabolism</subject><subject>Hepatocytes - pathology</subject><subject>Hepatocytes - virology</subject><subject>Humans</subject><subject>Interferon-alpha - pharmacology</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>RNA Viruses - genetics</subject><subject>RNA Viruses - isolation & purification</subject><subject>Transfection</subject><subject>Viral Core Proteins - metabolism</subject><subject>Viral Nonstructural Proteins - metabolism</subject><subject>Virus Replication</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1PwzAURS0EoqUw8AeQV4a0dhzH8Ygi2oLKx1BgtJzEbl3yJdul9N-T0gITy3vSe-fe4QBwidEQIxSOVnk7DBFKyBHoY8RZEMU0PAb97ocDTiPcA2fOrRBCnBNyCnqYkoRTGvZBO1Wt9MYbB1P4YezaQava0uTdsamhqaHzMiu30FtZO61yrwrYZSYhzFVZOtjapmq8cnC5K2p2x3UpLVzYZuOXUNYF9OuqsWahauWMOwcnWpZOXRz2ALyMb-fpNJg9Te7Sm1mQRyElAU8oJ5plKqaSRzrkumCJRIiobmQE6wRlLAuZpEnEWZERLTHXlDMVFSwmmAzA9b43t41zVmnRWlNJuxUYiZ010VkT39Y69mrPtuusUsUfedDUAaM9sDGl2v7fJO7T55_KYJ8wzqvP34S07yJmhFHx9jgRZE7J68N8LFLyBS9Xh6M</recordid><startdate>200412</startdate><enddate>200412</enddate><creator>Sun, Bill S.</creator><creator>Pan, Jingbo</creator><creator>Clayton, Marcy M.</creator><creator>Liu, Jie</creator><creator>Yan, Xiaoping</creator><creator>Matskevich, Alexey A.</creator><creator>Strayer, David S.</creator><creator>Gerber, Michael</creator><creator>Feitelson, Mark A.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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></search><sort><creationdate>200412</creationdate><title>Hepatitis C virus replication in stably transfected HepG2 cells promotes hepatocellular growth and tumorigenesis</title><author>Sun, Bill S. ; Pan, Jingbo ; Clayton, Marcy M. ; Liu, Jie ; Yan, Xiaoping ; Matskevich, Alexey A. ; Strayer, David S. ; Gerber, Michael ; Feitelson, Mark A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4253-98593f7be65a94f29fd78a003ea00b31f80b7b27a58497db3fa19f597e4d76313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Transformation, Neoplastic</topic><topic>Gene Expression Regulation, Viral</topic><topic>Hepacivirus - drug effects</topic><topic>Hepacivirus - genetics</topic><topic>Hepacivirus - physiology</topic><topic>Hepatocytes - metabolism</topic><topic>Hepatocytes - pathology</topic><topic>Hepatocytes - virology</topic><topic>Humans</topic><topic>Interferon-alpha - pharmacology</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>RNA Viruses - genetics</topic><topic>RNA Viruses - isolation & purification</topic><topic>Transfection</topic><topic>Viral Core Proteins - metabolism</topic><topic>Viral Nonstructural Proteins - metabolism</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Bill S.</creatorcontrib><creatorcontrib>Pan, Jingbo</creatorcontrib><creatorcontrib>Clayton, Marcy M.</creatorcontrib><creatorcontrib>Liu, Jie</creatorcontrib><creatorcontrib>Yan, Xiaoping</creatorcontrib><creatorcontrib>Matskevich, Alexey A.</creatorcontrib><creatorcontrib>Strayer, David S.</creatorcontrib><creatorcontrib>Gerber, Michael</creatorcontrib><creatorcontrib>Feitelson, Mark A.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Bill S.</au><au>Pan, Jingbo</au><au>Clayton, Marcy M.</au><au>Liu, Jie</au><au>Yan, Xiaoping</au><au>Matskevich, Alexey A.</au><au>Strayer, David S.</au><au>Gerber, Michael</au><au>Feitelson, Mark A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatitis C virus replication in stably transfected HepG2 cells promotes hepatocellular growth and tumorigenesis</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J. Cell. Physiol</addtitle><date>2004-12</date><risdate>2004</risdate><volume>201</volume><issue>3</issue><spage>447</spage><epage>458</epage><pages>447-458</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>HepG2 cells stably transfected with a full‐length, infectious hepatitis C virus (HCV) cDNA demonstrated consistent replication of HCV for more than 3 years. Intracellular minus strand HCV RNA was present. Minus strand synthesis was NS5B dependent, and was sensitive to interferon alpha (IFNα) treatment. NS5B and HCV core protein were detectable. HCV stimulated HepG2 cell growth and survival in culture, in soft agar, and accelerated tumor growth in SCID mice. These mice became HCV RNA positive in blood, where the virus was also sensitive to IFNα. The RNA banded at the density of HCV, and was resistant to RNase prior to extraction. Hence, HCV stably replicates in HepG2 cells, stimulates hepatocellular growth and tumorigenesis, and is susceptible to IFNα both in vitro and in vivo. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15389552</pmid><doi>10.1002/jcp.20083</doi><tpages>12</tpages></addata></record> |
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subjects | Animals Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic Gene Expression Regulation, Viral Hepacivirus - drug effects Hepacivirus - genetics Hepacivirus - physiology Hepatocytes - metabolism Hepatocytes - pathology Hepatocytes - virology Humans Interferon-alpha - pharmacology Mice Mice, SCID RNA Viruses - genetics RNA Viruses - isolation & purification Transfection Viral Core Proteins - metabolism Viral Nonstructural Proteins - metabolism Virus Replication |
title | Hepatitis C virus replication in stably transfected HepG2 cells promotes hepatocellular growth and tumorigenesis |
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