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Human cell types important for hepatitis C virus replication in vivo and in vitro: old assertions and current evidence.

Revie D, Salahuddin SZ - Virol. J. (2011)

Bottom Line: We analyzed 75 RT-PCR studies that tested for negative strand HCV RNA in liver and other human tissues. 85% of the studies that investigated extrahepatic replication of HCV found one or more samples positive for replicative RNA.These systems vary in their purposes and methods, but long term culturing of HCV in B cells, T cells, and other cell types has been used to analyze replication.It is therefore now possible to study HIV-HCV co-infections and HCV replication in vitro.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, California Lutheran University, Thousand Oaks, USA. revie@clunet.edu

ABSTRACT
Hepatitis C Virus (HCV) is a single stranded RNA virus which produces negative strand RNA as a replicative intermediate. We analyzed 75 RT-PCR studies that tested for negative strand HCV RNA in liver and other human tissues. 85% of the studies that investigated extrahepatic replication of HCV found one or more samples positive for replicative RNA. Studies using in situ hybridization, immunofluorescence, immunohistochemistry, and quasispecies analysis also demonstrated the presence of replicating HCV in various extrahepatic human tissues, and provide evidence that HCV replicates in macrophages, B cells, T cells, and other extrahepatic tissues. We also analyzed both short term and long term in vitro systems used to culture HCV. These systems vary in their purposes and methods, but long term culturing of HCV in B cells, T cells, and other cell types has been used to analyze replication. It is therefore now possible to study HIV-HCV co-infections and HCV replication in vitro.

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Genome organization of HCV.
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Figure 1: Genome organization of HCV.

Mentions: The HCV genome is about 9.6 kb in length. One large precursor protein is synthesized from an open reading frame of over 9024 nucleotides. This polyprotein is then cleaved to produce 10 proteins (Figure 1). These include three structural proteins at the amino end of the RNA transcript: Core and two envelope proteins (E1 and E2). An ion channel protein p7 is formed by cleavage of E2 [3]. Next are six proteins that are not in the viral particle (NS2, NS3, NS4A, NS4B, NS5A, and NS5B). In addition, a protein called F or ARFP can be produced from a frame-shift of the Core protein [4]. The viral RNA contains a 5' untranslated region (5'UTR), typically 341 nucleotides, that is highly conserved between the virus strains [5]. This region contains an internal ribosome entry site (IRES) for translation. The 3' end of the virus contains an untranslated region (3'UTR) that is 200 to 235 nucleotides long. It contains, in order, a variable region, a poly U/UC stretch, and a highly conserved 98 nucleotide sequence [6].


Human cell types important for hepatitis C virus replication in vivo and in vitro: old assertions and current evidence.

Revie D, Salahuddin SZ - Virol. J. (2011)

Genome organization of HCV.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3142522&req=5

Figure 1: Genome organization of HCV.
Mentions: The HCV genome is about 9.6 kb in length. One large precursor protein is synthesized from an open reading frame of over 9024 nucleotides. This polyprotein is then cleaved to produce 10 proteins (Figure 1). These include three structural proteins at the amino end of the RNA transcript: Core and two envelope proteins (E1 and E2). An ion channel protein p7 is formed by cleavage of E2 [3]. Next are six proteins that are not in the viral particle (NS2, NS3, NS4A, NS4B, NS5A, and NS5B). In addition, a protein called F or ARFP can be produced from a frame-shift of the Core protein [4]. The viral RNA contains a 5' untranslated region (5'UTR), typically 341 nucleotides, that is highly conserved between the virus strains [5]. This region contains an internal ribosome entry site (IRES) for translation. The 3' end of the virus contains an untranslated region (3'UTR) that is 200 to 235 nucleotides long. It contains, in order, a variable region, a poly U/UC stretch, and a highly conserved 98 nucleotide sequence [6].

Bottom Line: We analyzed 75 RT-PCR studies that tested for negative strand HCV RNA in liver and other human tissues. 85% of the studies that investigated extrahepatic replication of HCV found one or more samples positive for replicative RNA.These systems vary in their purposes and methods, but long term culturing of HCV in B cells, T cells, and other cell types has been used to analyze replication.It is therefore now possible to study HIV-HCV co-infections and HCV replication in vitro.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, California Lutheran University, Thousand Oaks, USA. revie@clunet.edu

ABSTRACT
Hepatitis C Virus (HCV) is a single stranded RNA virus which produces negative strand RNA as a replicative intermediate. We analyzed 75 RT-PCR studies that tested for negative strand HCV RNA in liver and other human tissues. 85% of the studies that investigated extrahepatic replication of HCV found one or more samples positive for replicative RNA. Studies using in situ hybridization, immunofluorescence, immunohistochemistry, and quasispecies analysis also demonstrated the presence of replicating HCV in various extrahepatic human tissues, and provide evidence that HCV replicates in macrophages, B cells, T cells, and other extrahepatic tissues. We also analyzed both short term and long term in vitro systems used to culture HCV. These systems vary in their purposes and methods, but long term culturing of HCV in B cells, T cells, and other cell types has been used to analyze replication. It is therefore now possible to study HIV-HCV co-infections and HCV replication in vitro.

Show MeSH
Related in: MedlinePlus