Replication of a hepatitis C virus replicon clone in mouse cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-12

AUTHORS

Susan L Uprichard, Josan Chung, Francis V Chisari, Takaji Wakita

ABSTRACT

BACKGROUND: Hepatitis C Virus (HCV) is a significant public health burden and small animal models are needed to study the pathology and immunobiology of the virus. In effort to develop experimental HCV mouse models, we screened a panel of HCV replicons to identify clones capable of replicating in mouse hepatocytes. RESULTS: We report the establishment of stable HCV replication in mouse hepatocyte and fibroblast cell lines using replicons derived from the JFH-1 genotype 2a consensus sequence. Viral RNA replication efficiency in mouse cells was comparable to that observed in human Huh-7 replicon cells, with negative-strand HCV RNA and the viral NS5A protein being readily detected by Northern and Western Blot analysis, respectively. Although HCV replication was established in the absence of adaptive mutations that might otherwise compromise the in vitro infectivity of the JFH-1 clone, no infectious virus was detected when the culture medium from full length HCV RNA replicating mouse cells was titrated on Huh-7 cells, suggesting that the mouse cells were unable to support production of infectious progeny viral particles. Consistent with an additional block in viral entry, infectious JFH-1 particles produced in Huh-7 cells were not able to establish detectable HCV RNA replication in naïve mouse cells. CONCLUSION: Thus, this report expands the repertoire of HCV replication systems and possibly represents a step toward developing mouse models of HCV replication, but it also highlights that other species restrictions might continue to make the development of a purely murine HCV infectious model challenging. More... »

PAGES

89

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1743-422x-3-89

DOI

http://dx.doi.org/10.1186/1743-422x-3-89

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036821662

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17069661


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