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| {{Hepatitis C}}
| | #REDIRECT [[Hepatitis C virus]] |
| {{CMG}}
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| ==Overview==
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| Hepatitis C virus (HCV) is a member of the genus ''[[Hepacivirus]]'' that belongs to the ''[[Flaviviridae]]'' family. It is an enveloped, [[single-stranded RNA]] virus that measures approximately 60 nm in diameter. The virus enters the cell using E1 and E2 envelope proteins. HCV RNA acts as template for the production of new proteins by [[translational]], [[co-translational]], and [[post-translational]] processes. These mechanisms lead to the synthesis of 10 proteins, 3 of which are structural and 7 of which are non-structural. In isolated acute HCV infection, the host [[immune system]] causes secretion of [[interferon-alpha]] and activation of [[natural killer cells]], along with proper activation of [[adaptive immune cells]]. [[Chronic HCV]] is characterized by the impairment of these mechanisms. Eventually, chronic HCV infection leads to local [[inflammation]] and [[fibrogenesis]] causing hepatic injury and cirrhosis. [[Hepatocellular carcinoma]], a known complication of chronic HCV infection, arises in cases of [[cirrhosis]]; the role of [[oncogenic proteins]] of HCV in the pathogenesis of [[hepatocellular carcinoma]] is yet to be elucidated.
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| ==Viral Characteristics==
| | [[Category:Emergency mdicine]] |
| Hepatitis C virus (HCV) is a member of the genus ''[[Hepacivirus]]'' that belongs to the ''[[Flaviviridae]]'' family. It is an enveloped, [[single-stranded RNA]] virus that measures approximately 60 nm in diameter.
| | [[Category:Disease]] |
| | | [[Category:Up-To-Date]] |
| ==Mode of Transmission==
| | [[Category:Infectious disease]] |
| HCV is primarily transmitted by blood. Exposure to blood is observed primarily in healthcare settings, such as in blood transfusions, surgical procedures, needle injuries, and [[hemodialysis]]. Also, the role of [[intravenous drug use]] has recently emerged as a great risk for viral transmission after the relatively successful control of nosocomial [[HCV transmission]].<ref name="pmid12407572">{{cite journal| author=National Institutes of Health| title=National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C: 2002--June 10-12, 2002. | journal=Hepatology | year= 2002 | volume= 36 | issue= 5 Suppl 1 | pages= S3-20 | pmid=12407572 | doi=10.1053/jhep.2002.37117 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12407572 }} </ref>
| | [[Category:Hepatology]] |
| | | [[Category:Gastroenterology]] |
| ==Life Cycle==
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| Humans are considered the only natural hosts for HCV. The full life cycle of the virus is poorly understood due to difficulty to culture ''in vitro''. The expression of E1-E2, two important envelope [[glycoprotein]] complexes, on the surface of HCV allows the virus to interact with host-cell molecules ([[glycosaminoglycans]]) by acting as ligands for cellular receptors, such as [[tetraspanin CD81]], scavenger receptor class B type I (SR-BI), and mannose binding lectins DC-SIGN and L-SIGN. This interaction is believed to have a crucial role in cell recognition and cellular tropism.<ref name="pmid11602769">{{cite journal| author=Op De Beeck A, Cocquerel L, Dubuisson J| title=Biogenesis of hepatitis C virus envelope glycoproteins. | journal=J Gen Virol | year= 2001 | volume= 82 | issue= Pt 11 | pages= 2589-95 | pmid=11602769 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11602769 }} </ref><ref name="pmid11356980">{{cite journal| author=Penin F, Combet C, Germanidis G, Frainais PO, Deléage G, Pawlotsky JM| title=Conservation of the conformation and positive charges of hepatitis C virus E2 envelope glycoprotein hypervariable region 1 points to a role in cell attachment. | journal=J Virol | year= 2001 | volume= 75 | issue= 12 | pages= 5703-10 | pmid=11356980 | doi=10.1128/JVI.75.12.5703-5710.2001 | pmc=PMC114285 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11356980 }} </ref><ref name="pmid12867431">{{cite journal| author=Barth H, Schafer C, Adah MI, Zhang F, Linhardt RJ, Toyoda H et al.| title=Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. | journal=J Biol Chem | year= 2003 | volume= 278 | issue= 42 | pages= 41003-12 | pmid=12867431 | doi=10.1074/jbc.M302267200 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12867431 }} </ref><ref name="pmid9794763">{{cite journal| author=Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R et al.| title=Binding of hepatitis C virus to CD81. | journal=Science | year= 1998 | volume= 282 | issue= 5390 | pages= 938-41 | pmid=9794763 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9794763 }} </ref><ref name="pmid12913001">{{cite journal| author=Bartosch B, Vitelli A, Granier C, Goujon C, Dubuisson J, Pascale S et al.| title=Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor. | journal=J Biol Chem | year= 2003 | volume= 278 | issue= 43 | pages= 41624-30 | pmid=12913001 | doi=10.1074/jbc.M305289200 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12913001 }} </ref><ref name="pmid12761383">{{cite journal| author=Hsu M, Zhang J, Flint M, Logvinoff C, Cheng-Mayer C, Rice CM et al.| title=Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. | journal=Proc Natl Acad Sci U S A | year= 2003 | volume= 100 | issue= 12 | pages= 7271-6 | pmid=12761383 | doi=10.1073/pnas.0832180100 | pmc=PMC165865 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12761383 }} </ref><ref name="pmid12356718">{{cite journal| author=Scarselli E, Ansuini H, Cerino R, Roccasecca RM, Acali S, Filocamo G et al.| title=The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. | journal=EMBO J | year= 2002 | volume= 21 | issue= 19 | pages= 5017-25 | pmid=12356718 | doi= | pmc=PMC129051 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12356718 }} </ref><ref name="pmid12609975">{{cite journal| author=Lozach PY, Lortat-Jacob H, de Lacroix de Lavalette A, Staropoli I, Foung S, Amara A et al.| title=DC-SIGN and L-SIGN are high affinity binding receptors for hepatitis C virus glycoprotein E2. | journal=J Biol Chem | year= 2003 | volume= 278 | issue= 22 | pages= 20358-66 | pmid=12609975 | doi=10.1074/jbc.M301284200 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12609975 }} </ref><ref name="pmid12634366">{{cite journal| author=Pöhlmann S, Zhang J, Baribaud F, Chen Z, Leslie GJ, Lin G et al.| title=Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. | journal=J Virol | year= 2003 | volume= 77 | issue= 7 | pages= 4070-80 | pmid=12634366 | doi= | pmc=PMC150620 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12634366 }} </ref> The exact mechanism by which viral genome enters the host cell is poorly understood, but it is believed to be via receptor-mediated endocytosis. Then envelope glycoproteins utilize pH-dependent mechanisms to mediate fusion of the [[viral envelope]] using [[endosomal membrane]].<ref name="pmid12913001">{{cite journal| author=Bartosch B, Vitelli A, Granier C, Goujon C, Dubuisson J, Pascale S et al.| title=Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor. | journal=J Biol Chem | year= 2003 | volume= 278 | issue= 43 | pages= 41624-30 | pmid=12913001 | doi=10.1074/jbc.M305289200 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12913001 }} </ref><ref name="pmid12761383">{{cite journal| author=Hsu M, Zhang J, Flint M, Logvinoff C, Cheng-Mayer C, Rice CM et al.| title=Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. | journal=Proc Natl Acad Sci U S A | year= 2003 | volume= 100 | issue= 12 | pages= 7271-6 | pmid=12761383 | doi=10.1073/pnas.0832180100 | pmc=PMC165865 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12761383 }} </ref> As soon as it is released into the cytoplasm, the viral nucleocapsid uncoats by unknown mechanisms.
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| Template [[HCV RNA]] allows viral replication to take place and protein synthesis is thus facilitated. Cap-independent protein translation takes place when [[ribosomal 40S subunit]] binds to [[internal ribosome entry site]] ([[IRES]]).<ref name="pmid1310759">{{cite journal| author=Tsukiyama-Kohara K, Iizuka N, Kohara M, Nomoto A| title=Internal ribosome entry site within hepatitis C virus RNA. | journal=J Virol | year= 1992 | volume= 66 | issue= 3 | pages= 1476-83 | pmid=1310759 | doi= | pmc=PMC240872 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1310759 }} </ref> IRES is a [[stem-loop structure]] that is located at the [[5' untranslated region]] ([[UTR]]) of the virus and the initial 30-40 [[nucleotides]] of the viral core-encoding region.<ref name="pmid1310759">{{cite journal| author=Tsukiyama-Kohara K, Iizuka N, Kohara M, Nomoto A| title=Internal ribosome entry site within hepatitis C virus RNA. | journal=J Virol | year= 1992 | volume= 66 | issue= 3 | pages= 1476-83 | pmid=1310759 | doi= | pmc=PMC240872 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1310759 }} </ref> Nonetheless, full polyprotein translation also requires the use of 80S ribosomes and the viral [[3' UTR]], both of which presumably play a role in regulation of the translational process.<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref>
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| [[Translation]] is accompanied by co-translational processes and followed by post-translational processes; all of which yield a total of 10 mature proteins.<ref name="pmid7679746">{{cite journal| author=Grakoui A, Wychowski C, Lin C, Feinstone SM, Rice CM| title=Expression and identification of hepatitis C virus polyprotein cleavage products. | journal=J Virol | year= 1993 | volume= 67 | issue= 3 | pages= 1385-95 | pmid=7679746 | doi= | pmc=PMC237508 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7679746 }} </ref>
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| The following proteins are produced:
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| ====Structural Proteins:====
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| *Core (C) protein<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref>
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| *Envelope 1 (E1) glycoprotein<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref>
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| *Envelope 2 (E2) glycoprotein<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref>
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| C, E1, and E2 are separated from the remaining 7 non-structural proteins by the activity of p7, a small membrane polypeptide that belongs to viroporin family.<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref> The 3 proteins are released by the activity of signal peptidases mediated by the host cell.
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| ====Non-Structural (NS) Proteins:====
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| *NS2: Zn-dependent [[proteinase]]<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref><ref name="pmid14752815">{{cite journal| author=Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM| title=Structural biology of hepatitis C virus. | journal=Hepatology | year= 2004 | volume= 39 | issue= 1 | pages= 5-19 | pmid=14752815 | doi=10.1002/hep.20032 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14752815 }} </ref>
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| *NS3: Serine-dependent [[proteinase]], [[helicase]], and [[NTPase]]<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref><ref name="pmid14752815">{{cite journal| author=Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM| title=Structural biology of hepatitis C virus. | journal=Hepatology | year= 2004 | volume= 39 | issue= 1 | pages= 5-19 | pmid=14752815 | doi=10.1002/hep.20032 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14752815 }} </ref>
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| *NS4A: Cofactor NS3 [[proteinase]]<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref><ref name="pmid14752815">{{cite journal| author=Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM| title=Structural biology of hepatitis C virus. | journal=Hepatology | year= 2004 | volume= 39 | issue= 1 | pages= 5-19 | pmid=14752815 | doi=10.1002/hep.20032 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14752815 }} </ref>
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| *NS4B: [[Membrane anchor]]<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref><ref name="pmid14752815">{{cite journal| author=Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM| title=Structural biology of hepatitis C virus. | journal=Hepatology | year= 2004 | volume= 39 | issue= 1 | pages= 5-19 | pmid=14752815 | doi=10.1002/hep.20032 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14752815 }} </ref>
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| *NS5A: Regulation of [[RNA polymerase]] activity and inhibition of antiviral activity of [[interferon]]<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref><ref name="pmid14752815">{{cite journal| author=Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM| title=Structural biology of hepatitis C virus. | journal=Hepatology | year= 2004 | volume= 39 | issue= 1 | pages= 5-19 | pmid=14752815 | doi=10.1002/hep.20032 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14752815 }} </ref>
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| *NS5B: RNA-dependent [[RNA polymerase]]<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref><ref name="pmid14752815">{{cite journal| author=Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM| title=Structural biology of hepatitis C virus. | journal=Hepatology | year= 2004 | volume= 39 | issue= 1 | pages= 5-19 | pmid=14752815 | doi=10.1002/hep.20032 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14752815 }} </ref>
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| *p7: Separation of structural from non-structural proteins and possible formation of [[ion channel]]<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref><ref name="pmid14752815">{{cite journal| author=Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM| title=Structural biology of hepatitis C virus. | journal=Hepatology | year= 2004 | volume= 39 | issue= 1 | pages= 5-19 | pmid=14752815 | doi=10.1002/hep.20032 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14752815 }} </ref>
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| Non-structural proteins NS3 to NS5B play an important role in the formation of a replication complex that includes an intracellular "membranous web", at least partially derived from host [[endoplasmic reticulum]].<ref name="pmid12021330">{{cite journal| author=Egger D, Wölk B, Gosert R, Bianchi L, Blum HE, Moradpour D et al.| title=Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. | journal=J Virol | year= 2002 | volume= 76 | issue= 12 | pages= 5974-84 | pmid=12021330 | doi= | pmc=PMC136238 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12021330 }} </ref> The replication complex is responsible for synthesis template negative-strand RNA and consequent synthesis of its positive-strand counterpart. These RNA molecules are then enclosed in new [[virion]]s.
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| ===Formation of Nucleocapsid and Envelope===
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| New HCV nucleocapsid is formed by the action of core [[protein C]] along with viral genomic positive-strand RNA.<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref> The envelope of the newly formed nucleocapsid is later formed by budding action into the lumen of the [[endoplasmic reticulum]]. Nonetheless, envelope [[glycoproteins]] do not yet mature early on at this stage. When new virions are exported outside the host cell, via cellular secretory mechanisms, glycoproteins of the envelope finally mature.<ref name="pmid15036326">{{cite journal| author=Pawlotsky JM| title=Pathophysiology of hepatitis C virus infection and related liver disease. | journal=Trends Microbiol | year= 2004 | volume= 12 | issue= 2 | pages= 96-102 | pmid=15036326 | doi=10.1016/j.tim.2003.12.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15036326 }} </ref>
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| ==References==
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