DOI: 10.1073/pnas.212532699. Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees

Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees

10.1073/pnas.212532699

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The development of a subgenomic replicon derived from the hepatitis C virus (HCV) strain Con1 enabled the study of viral RNA replication in Huh-7 cells. The level of replication of replicons, as well as full-length Con1 genomes, increased significantly by a combination of two adaptive mutations in NS3 (E1202G and T1280I) and a single mutation in NS5A (S2197P). However, these cell culture-adaptive mutations influenced in vivo infectivity. After intrahepatic transfection of chimpanzees, the wild-type Con1 genome was infectious and produced viral titers similar to those produced by other infectious HCV clones. Repeated independent transfections with RNA transcripts of a Con1 genome containing the three adaptive mutations failed to achieve active HCV infection. Furthermore, although a chimpanzee transfected with RNA transcripts of a Con1 genome with only the NS5A mutation became infected, this mutation was detected only in virus genomes recovered from serum at day 4; viruses recovered at day 7 had a reversion back to the original Con1 sequence. Our study demonstrates that mutations that are adaptive for replication of HCV in cell culture may be highly attenuating in vivo .

Bibliography

Bukh, J., Pietschmann, T., Lohmann, V., Krieger, N., Faulk, K., Engle, R. E., Govindarajan, S., Shapiro, M., St. Claire, M., & Bartenschlager, R. (2002). Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees. Proceedings of the National Academy of Sciences, 99(22), 14416â14421.

Authors 10

Jens Bukh (first)
Thomas Pietschmann (additional)
Volker Lohmann (additional)
Nicole Krieger (additional)
Kristina Faulk (additional)
Ronald E. Engle (additional)
Sugantha Govindarajan (additional)
Max Shapiro (additional)
Marisa St. Claire (additional)
Ralf Bartenschlager (additional)

References 44 Referenced 218

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Dates

Type	When
Created	22 years, 10 months ago (Oct. 29, 2002, 12:24 p.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 7:57 a.m.)
Indexed	2 days, 19 hours ago (Sept. 4, 2025, 10:02 a.m.)
Issued	22 years, 10 months ago (Oct. 21, 2002)
Published	22 years, 10 months ago (Oct. 21, 2002)
Published Online	22 years, 10 months ago (Oct. 21, 2002)
Published Print	22 years, 10 months ago (Oct. 29, 2002)

Funders 0

None

BibTeX

@article{Bukh_2002, title={Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.212532699}, DOI={10.1073/pnas.212532699}, number={22}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Bukh, Jens and Pietschmann, Thomas and Lohmann, Volker and Krieger, Nicole and Faulk, Kristina and Engle, Ronald E. and Govindarajan, Sugantha and Shapiro, Max and St. Claire, Marisa and Bartenschlager, Ralf}, year={2002}, month=oct, pages={14416–14421} }

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  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
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        10,
        21
      ]
    ]
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}