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Self-Enhancement of Hepatitis C Virus Replication by Promotion of Specific Sphingolipid Biosynthesis
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نویسنده
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hirata y. ,ikeda k. ,sudoh m. ,tokunaga y. ,suzuki a. ,weng l. ,ohta m. ,tobita y. ,okano k. ,ozeki k. ,kawasaki k. ,tsukuda t. ,katsume a. ,aoki y. ,umehara t. ,sekiguchi s. ,toyoda t. ,shimotohno k. ,soga t. ,nishijima m. ,taguchi r. ,kohara m.
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منبع
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plos pathogens - 2012 - دوره : 8 - شماره : 8
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چکیده
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Lipids are key components in the viral life cycle that affect host-pathogen interactions. in this study,we investigated the effect of hcv infection on sphingolipid metabolism,especially on endogenous sm levels,and the relationship between hcv replication and endogenous sm molecular species. we demonstrated that hcv induces the expression of the genes (sgms1 and 2) encoding human sm synthases 1 and 2. we observed associated increases of both total and individual sphingolipid molecular species,as assessed in human hepatocytes and in the detergent-resistant membrane (drm) fraction in which hcv replicates. sgms1 expression had a correlation with hcv replication. inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (spt) inhibitor,na808,suppressed hcv-rna production while also interfering with sphingolipid metabolism. further,we identified the sm molecular species that comprise the drm fraction and demonstrated that these endogenous sm species interacted with hcv nonstructural 5b polymerase to enhance viral replication. our results reveal that hcv alters sphingolipid metabolism to promote viral replication,providing new insights into the formation of the hcv replication complex and the involvement of host lipids in the hcv life cycle. © 2012 hirata et al.
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آدرس
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department of microbiology and cell biology,tokyo metropolitan institute of medical science,setagaya-ku,tokyo, Japan, department of metabolome,graduate school of medicine,the university of tokyo,bunkyo-ku,tokyo,japan,institute for advanced biosciences,keio university,kakuganji,tsuruoka,yamagata, Japan, kamakura research laboratories,chugai pharmaceutical co.,ltd,kamakura,kanagawa, Japan, department of microbiology and cell biology,tokyo metropolitan institute of medical science,setagaya-ku,tokyo, Japan, institute of glycoscience,tokai university,hiratsuka-shi,kanagawa, Japan, unit of viral genome regulation,institut pasteur of shanghai,key laboratory of molecular virology and immunology,chinese academy of sciences,shanghai, China, institute for advanced biosciences,keio university,kakuganji,tsuruoka,yamagata, Japan, department of microbiology and cell biology,tokyo metropolitan institute of medical science,setagaya-ku,tokyo, Japan, fuji-gotemba research laboratories,chugai pharmaceutical co.,ltd,gotemba,shizuoka, Japan, fuji-gotemba research laboratories,chugai pharmaceutical co.,ltd,gotemba,shizuoka, Japan, kamakura research laboratories,chugai pharmaceutical co.,ltd,kamakura,kanagawa, Japan, kamakura research laboratories,chugai pharmaceutical co.,ltd,kamakura,kanagawa, Japan, kamakura research laboratories,chugai pharmaceutical co.,ltd,kamakura,kanagawa, Japan, kamakura research laboratories,chugai pharmaceutical co.,ltd,kamakura,kanagawa, Japan, department of microbiology and cell biology,tokyo metropolitan institute of medical science,setagaya-ku,tokyo, Japan, department of microbiology and cell biology,tokyo metropolitan institute of medical science,setagaya-ku,tokyo, Japan, unit of viral genome regulation,institut pasteur of shanghai,key laboratory of molecular virology and immunology,chinese academy of sciences,shanghai, China, research institute,chiba institute of technology,narashino,chiba, Japan, institute for advanced biosciences,keio university,kakuganji,tsuruoka,yamagata, Japan, national institute of health sciences,setagaya-ku,tokyo,japan,showa pharmaceutical university,machidashi,tokyo, Japan, department of metabolome,graduate school of medicine,the university of tokyo,bunkyo-ku,tokyo,japan,department of biomedical sciences,college of life and health sciences,chubu university,kasugai-shi,aichi, Japan, department of microbiology and cell biology,tokyo metropolitan institute of medical science,setagaya-ku,tokyo, Japan
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Authors
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