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Udgivet

High density Huh7.5 cell hollow fiber bioreactor culture for high-yield production of hepatitis C virus and studies of antivirals

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Development of a downstream process for the production of an inactivated whole hepatitis C virus vaccine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Discrete finger sequences are widely represented in human striatum

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Author Correction: Assessment of brain reference genes for RT-qPCR studies in neurodegenerative diseases

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Development of a downstream process for the production of an inactivated whole hepatitis C virus vaccine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Global and local envelope protein dynamics of hepatitis C virus determine broad antibody sensitivity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. An alternate conformation of HCV E2 neutralizing face as an additional vaccine target

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Chronic hepatitis C virus (HCV) infection poses a serious global public health burden. Despite the recent development of effective treatments there is a large unmet need for a prophylactic vaccine. Further, antiviral resistance might compromise treatment efficiency in the future. HCV cell culture systems are typically based on Huh7 and derived hepatoma cell lines cultured in monolayers. However, efficient high cell density culture systems for high-yield HCV production and studies of antivirals are lacking. We established a system based on Huh7.5 cells cultured in a hollow fiber bioreactor in the presence or absence of bovine serum. Using an adapted chimeric genotype 5a virus, we achieved peak HCV infectivity and RNA titers of 7.6 log10 FFU/mL and 10.4 log10 IU/mL, respectively. Bioreactor derived HCV showed high genetic stability, as well as buoyant density, sensitivity to neutralizing antibodies AR3A and AR4A, and dependency on HCV co-receptors CD81 and SR-BI comparable to that of HCV produced in monolayer cell cultures. Using the bioreactor platform, treatment with the NS5A inhibitor daclatasvir resulted in HCV escape mediated by the NS5A resistance substitution Y93H. In conclusion, we established an efficient high cell density HCV culture system with implications for studies of antivirals and vaccine development.

OriginalsprogEngelsk
TidsskriftScientific Reports
Vol/bind8
Udgave nummer17505
ISSN2045-2322
DOI
StatusUdgivet - 30 nov. 2018

ID: 55820940