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The HCV life cycle: in vitro tissue culture systems and therapeutic targets
TWINCORE – Institute of Experimental Virology, Centre for Experimental and Clinical Infection Research, Hannover , Germany. (Gisa Gerold)
2014 (English)In: Digestive Diseases, ISSN 0257-2753, E-ISSN 1421-9875, Vol. 32, no 5, p. 525-537Article in journal (Refereed) Published
Abstract [en]

Hepatitis C virus (HCV) is a highly variable plus-strand RNA virus of the family Flaviviridae. Viral strains are grouped into six epidemiologically relevant genotypes that differ from each other by more than 30% at the nucleotide level. The variability of HCV allows immune evasion and facilitates persistence. It is also a substantial challenge for the development of specific antiviral therapies effective across all HCV genotypes and for prevention of drug resistance. Novel HCV cell culture models were instrumental for identification and profiling of therapeutic strategies. Concurrently, these models revealed numerous host factors critical for HCV propagation, some of which have emerged as targets for antiviral therapy. It is generally assumed that the use of host factors is conserved among HCV isolates and genotypes. Additionally, the barrier to viral resistance is thought to be high when interfering with host factors. Therefore, current drug development includes both targeting of viral factors but also of host factors essential for virus replication. In fact, some of these host-targeting agents, for instance inhibitors of cyclophilin A, have advanced to late stage clinical trials. Here, we highlight currently available cell culture systems for HCV, review the most prominent host-targeting strategies against hepatitis C and critically discuss opportunities and risks associated with host-targeting antiviral strategies.

Place, publisher, year, edition, pages
S. Karger, 2014. Vol. 32, no 5, p. 525-537
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:umu:diva-148160DOI: 10.1159/000360830ISI: 000339145500006PubMedID: 25034285OAI: oai:DiVA.org:umu-148160DiVA, id: diva2:1210797
Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-10-11Bibliographically approved

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