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Udgivet

Recombinant hepatitis C virus genotype 5a infectious cell culture systems expressing minimal JFH1 NS5B sequences permit polymerase inhibitor studies

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Production and characterization of high-titer serum-free cell culture grown hepatitis C virus particles of genotype 1-6

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Non-genotype-specific role of the hepatitis C virus 5' untranslated region in virus production and in inhibition by interferon

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Genome Sequence of an Unknown Subtype of Hepatitis C Virus Genotype 6: Another Piece for the Taxonomic Puzzle

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Virus Adaptation and Selection Following Challenge of Animals Vaccinated against Classical Swine Fever Virus

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Replicons of a rodent hepatitis C model virus permit selection of highly permissive cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

The six major epidemiologically important hepatitis C virus (HCV) genotypes differ in global distribution and antiviral responses. Full-length infectious cell-culture adapted clones, the gold standard for HCV studies in vitro, are missing for genotypes 4 and 5. To address this challenge for genotype 5, we constructed a consensus full-length clone of strain SA13 (SA13fl), which was found non-viable in Huh7.5 cells. Step-wise adaptation of SA13fl-based recombinants, beginning with a virus encoding the NS5B-thumb domain and 3´UTR of JFH1 (SA13/JF372-X), resulted in a high-titer SA13 virus with only 41 JFH1-encoded NS5B-thumb residues (SA13/JF470-510cc); this required sixteen cell-culture adaptive substitutions within the SA13fl polyprotein and two 3´UTR-changes. SA13/JF372-X and SA13/JF470-510cc were equally sensitive to nucleoside polymerase inhibitors, including sofosbuvir, but showed differential sensitivity to inhibitors targeting the NS5B palm or thumb. SA13/JF470-510cc represents a model to elucidate the influence of HCV RNA elements on viral replication and map determinants of sensitivity to polymerase inhibitors.

OriginalsprogEngelsk
TidsskriftVirology
Vol/bind522
Sider (fra-til)177-192
Antal sider16
ISSN0042-6822
DOI
StatusUdgivet - 1 sep. 2018

ID: 55377615