Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-11

AUTHORS

Megumi Tasaka-Fujita, Nao Sugiyama, Wonseok Kang, Takahiro Masaki, Asako Murayama, Norie Yamada, Ryuichi Sugiyama, Senko Tsukuda, Koichi Watashi, Yasuhiro Asahina, Naoya Sakamoto, Takaji Wakita, Eui-Cheol Shin, Takanobu Kato

ABSTRACT

Amino acid (aa) polymorphisms in the hepatitis C virus (HCV) genotype 1b core protein have been reported to be a potent predictor for poor response to interferon (IFN)-based therapy and a risk factor for hepatocarcinogenesis. We investigated the effects of these polymorphisms with genotype 1b/2a chimeric viruses that contained polymorphisms of Arg/Gln at aa 70 and Leu/Met at aa 91. We found that infectious virus production was reduced in cells transfected with chimeric virus RNA that had Gln at aa 70 (aa70Q) compared with RNA with Arg at aa 70 (aa70R). Using flow cytometry analysis, we confirmed that HCV core protein accumulated in aa70Q clone transfected cells, and it caused a reduction in cell-surface expression of major histocompatibility complex (MHC) class I molecules induced by IFN treatment through enhanced protein kinase R phosphorylation. We could not detect any effects due to the polymorphism at aa 91. In conclusion, the polymorphism at aa 70 was associated with efficiency of infectious virus production, and this deteriorated virus production in strains with aa70Q resulted in the intracellular accumulation of HCV proteins and attenuation of MHC class I molecule expression. These observations may explain the strain-associated resistance to IFN-based therapy and hepatocarcinogenesis of HCV. More... »

PAGES

13994

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep13994

DOI

http://dx.doi.org/10.1038/srep13994

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021266360

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26365522


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