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.
Highlights
The majority of the current research on human hepatitis C virus (HCV) is unusual in that it does not study the natural virus, but instead studies are based on synthetic constructs and their manipulations
Detection of extrahepatic HCV replication by other methods As Reverse transcriptase (RT)-PCR has established that HCV negative strands are found in various tissues and cell types, we examine other evidence that HCV replicates in extrahepatic tissues
Another method to study HCV replication is to separate the components of peripheral blood mononuclear cells (PBMC), infect the different cell types, and determine which cells are positive for HCV
Summary
The majority of the current research on human hepatitis C virus (HCV) is unusual in that it does not study the natural virus, but instead studies are based on synthetic constructs and their manipulations. If the abstract did not mention negative strands of HCV or NS proteins, we probably did not include the study in our analysis, except for the papers that looked at quasispecies or binding of the virus. Since much of the HCV in serum is complexed with antibodies, one study investigated infection of monocytic (U937 and Monomac-6) and T lymphocytic (MOLT-4 and Jurkat) cell lines [22]. There is strong evidence that HCV can bind and enter various cell types found outside the liver, and the process of infection can be studied in vitro [23]. PBMC was found to contain negative strand HCV RNA by many investigators (Table 1), causing others to investigate infection of particular cell types in PBMC as well as various other
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