Prominent steatosis with hypermetabolism of the cell line permissive for years of infection with hepatitis C virus

Kazuo Sugiyama, Hirotoshi Ebinuma, Nobuhiro Nakamoto, Noriko Sakasegawa, Yuko Murakami, Hakusyo Cho, Shingo Usui, Yuka Ishibashi, Yuko Wakayama, Nobuhito Taniki, Hiroko Murata, Yoshimasa Saito, Masayoshi Fukasawa, Kyoko Saito, Yoshiyuki Yamagishi, Takaji Wakita, Hiroshi Takaku, Toshifumi Hibi, Hidetsugu Saito, Takanori Kanai

研究成果: Article

18 引用 (Scopus)

抄録

Most of experiments for HCV infection have been done using lytic infection systems, in which HCV-infected cells inevitably die. Here, to elucidate metabolic alteration in HCV-infected cells in a more stable condition, we established an HCV-persistently- infected cell line, designated as HPI cells. This cell line has displayed prominent steatosis and supported HCV infection for more than 2 years, which is the longest ever reported. It enabled us to analyze metabolism in the HCV-infected cells integrally combining metabolomics and expression arrays. It revealed that rate-limiting enzymes for biosynthesis of cholesterol and fatty acids were up-regulated with actual increase in cholesterol, desmosterol (cholesterol precursor) and pool of fatty acids. Notably, the pentose phosphate pathway was facilitated with marked up-regulation of glucose-6- phosphate dehydrogenase, a rete-limiting enzyme, with actual increase in NADPH. In its downstream, enzymes for purine synthesis were also up-regulated resulting in increase of purine. Contrary to common cancers, the TCA cycle was preferentially facilitated comparing to glycolysis pathway with a marked increase of most of amino acids. Interestingly, some genes controlled by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master regulator of antioxidation and metabolism, were constitutively up-regulated in HPI cells. Knockdown of Nrf2 markedly reduced steatosis and HCV infection, indicating that Nrf2 and its target genes play important roles in metabolic alteration and HCV infection. In conclusion, HPI cell is a bona fide HCV-persistently-infected cell line supporting HCV infection for years. This cell line sustained prominent steatosis in a hypermetabolic status producing various metabolites. Therefore, HPI cell is a potent research tool not only for persistent HCV infection but also for liver metabolism, overcoming drawbacks of the lytic infection systems.

元の言語English
記事番号e94460
ジャーナルPLoS One
9
発行部数4
DOI
出版物ステータスPublished - 2014 4 9

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Hepatitis C virus
Viruses
Hepacivirus
Cells
cell lines
Metabolism
Cell Line
Cholesterol
Infection
infection
Enzymes
Fatty Acids
Desmosterol
Genes
Pentoses
cells
Glucosephosphate Dehydrogenase
Biosynthesis
cholesterol
purines

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

これを引用

Prominent steatosis with hypermetabolism of the cell line permissive for years of infection with hepatitis C virus. / Sugiyama, Kazuo; Ebinuma, Hirotoshi; Nakamoto, Nobuhiro; Sakasegawa, Noriko; Murakami, Yuko; Cho, Hakusyo; Usui, Shingo; Ishibashi, Yuka; Wakayama, Yuko; Taniki, Nobuhito; Murata, Hiroko; Saito, Yoshimasa; Fukasawa, Masayoshi; Saito, Kyoko; Yamagishi, Yoshiyuki; Wakita, Takaji; Takaku, Hiroshi; Hibi, Toshifumi; Saito, Hidetsugu; Kanai, Takanori.

:: PLoS One, 巻 9, 番号 4, e94460, 09.04.2014.

研究成果: Article

Sugiyama, K, Ebinuma, H, Nakamoto, N, Sakasegawa, N, Murakami, Y, Cho, H, Usui, S, Ishibashi, Y, Wakayama, Y, Taniki, N, Murata, H, Saito, Y, Fukasawa, M, Saito, K, Yamagishi, Y, Wakita, T, Takaku, H, Hibi, T, Saito, H & Kanai, T 2014, 'Prominent steatosis with hypermetabolism of the cell line permissive for years of infection with hepatitis C virus', PLoS One, 巻. 9, 番号 4, e94460. https://doi.org/10.1371/journal.pone.0094460
Sugiyama, Kazuo ; Ebinuma, Hirotoshi ; Nakamoto, Nobuhiro ; Sakasegawa, Noriko ; Murakami, Yuko ; Cho, Hakusyo ; Usui, Shingo ; Ishibashi, Yuka ; Wakayama, Yuko ; Taniki, Nobuhito ; Murata, Hiroko ; Saito, Yoshimasa ; Fukasawa, Masayoshi ; Saito, Kyoko ; Yamagishi, Yoshiyuki ; Wakita, Takaji ; Takaku, Hiroshi ; Hibi, Toshifumi ; Saito, Hidetsugu ; Kanai, Takanori. / Prominent steatosis with hypermetabolism of the cell line permissive for years of infection with hepatitis C virus. :: PLoS One. 2014 ; 巻 9, 番号 4.
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AU - Sugiyama, Kazuo

AU - Ebinuma, Hirotoshi

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AU - Sakasegawa, Noriko

AU - Murakami, Yuko

AU - Cho, Hakusyo

AU - Usui, Shingo

AU - Ishibashi, Yuka

AU - Wakayama, Yuko

AU - Taniki, Nobuhito

AU - Murata, Hiroko

AU - Saito, Yoshimasa

AU - Fukasawa, Masayoshi

AU - Saito, Kyoko

AU - Yamagishi, Yoshiyuki

AU - Wakita, Takaji

AU - Takaku, Hiroshi

AU - Hibi, Toshifumi

AU - Saito, Hidetsugu

AU - Kanai, Takanori

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