Development of JFH1-based cell culture systems for hepatitis C virus genotype 4a and evidence for cross-genotype neutralization

Proceedings of the National Academy of Sciences of the United States of America
Troels K ScheelJens Bukh

Abstract

Efficient in vitro systems to study the life cycle of hepatitis C virus (HCV) were recently developed for JFH1 (genotype 2a), which has unique replication capacity in Huh7 cells. We developed 4a/JFH1 intergenotypic recombinants containing the structural genes (Core, E1, and E2), p7, and all or part of NS2 of the 4a prototype strain ED43 that, after transfection of Huh7.5 cells with RNA transcripts, produced infectious viruses. Compared with the J6/JFH control virus, production of viruses was delayed. However, efficient spread of infection and high HCV RNA and infectivity titers were obtained in serial passages. Sequence analysis of recovered viruses and subsequent reverse genetic studies revealed a vital dependence on one or two NS2 mutations, depending on the 4a/2a junction. Infectivity of ED43/JFH1 viruses was CD81 dependent. The genotype 4 cell culture systems permit functional analyses as well as drug and vaccine research on an increasingly important genotype in the Middle East, Africa, and Europe. We also developed genotype 1a intergenotypic recombinants from H77C with vital mutations in NS3. Using H77C/JFH1 and ED43/JFH1 viruses, we demonstrated high homologous neutralizing antibody titers in 1a and 4a patient sera, respe...Continue Reading

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Citations

Oct 21, 2010·Virologica Sinica·Susan L Uprichard
Mar 16, 2013·Bioorganic & Medicinal Chemistry·Hong-Kui CuiLei Liu
Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yi-Ping LiJens Bukh
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Erick GiangMansun Law
Apr 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yi-Ping LiJens Bukh
Nov 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yi-Ping LiJens Bukh
Dec 25, 2012·Molecular & Cellular Proteomics : MCP·Hui SunXijun Wang
Feb 3, 2009·British Medical Bulletin·Brian J Thomson
Sep 8, 2011·Antimicrobial Agents and Chemotherapy·Philip MeulemanJean Dubuisson
Feb 15, 2013·Journal of Virology·Cynthia de la FuenteCharles M Rice
Oct 12, 2012·International Journal of Hepatology·Garrick K Wilson, Zania Stamataki
Jun 21, 2011·Annual Review of Microbiology·Catherine L Murray, Charles M Rice
Oct 23, 2012·Current Opinion in Virology·Ana Shulla, Glenn Randall
Apr 3, 2012·Gastroenterology·Sibylle HaidThomas Pietschmann

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