期刊
GASTROENTEROLOGY
卷 144, 期 1, 页码 59-U146出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2012.09.033
关键词
Pan-Genotypic; Q34R; Cured Huh-7 Cell Line; GS-5885; GS-7977
Despite the prevalence of hepatitis C virus genotype 4, no replicon system is available for study of the genotype. To facilitate discovery and development of reagents against this virus, we synthesized and transcribed a genotype 4a subgenomic replicon and transfected Huh7-Lunet cells with it, which yielded very few colonies. However, when we used a new Huh7-derived cell line, colony formation increased similar to 70-fold. We identified multiple adaptive mutations in the virus's nonstructural 3 or 4A proteins that allowed the cells to maintain stable, genotype 4a luciferase-encoding replicons. Several classes of hepatitis C virus inhibitors had different antiviral effects on genotypes 4a vs 1b. The genotype 4a replicon system we created will aid in the development of treatment regimens for all genotypes of hepatitis C virus.
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