Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV

• Published in: Nature communications 2016-07, Vol.7 (1), p.12203-12203, Article 12203
• Main Authors: Akil, Abdellah, Peng, Juan, Omrane, Mohyeddine, Gondeau, Claire, Desterke, Christophe, Marin, Mickaël, Tronchère, Hélène, Taveneau, Cyntia, Sar, Sokhavuth, Briolotti, Philippe, Benjelloun, Soumaya, Benjouad, Abdelaziz, Maurel, Patrick, Thiers, Valérie, Bressanelli, Stéphane, Samuel, Didier, Bréchot, Christian, Gassama-Diagne, Ama
• Format: Article
• Language: English
• Subjects: 13/106; 13/107; 13/109; 13/89; 13/95; 14; 14/19; 631/250/255/234/2513/1551; 631/443/319/2723; 631/80/86/2365; 82; 82/29; 82/83; 96; Biosynthesis; Cell Line, Tumor; Gene Expression Regulation; Hepacivirus - pathogenicity; Hepacivirus - physiology; Hepatitis C; Hepatitis C - metabolism; Host-Pathogen Interactions - physiology; Human health and pathology; Humanities and Social Sciences; Humans; Hépatology and Gastroenterology; Infections; Infectious diseases; Kinases; Life Sciences; Lipid Droplets - drug effects; Lipid Droplets - metabolism; Lipid Metabolism - physiology; Lipids; Liver cancer; Liver cirrhosis; Liver Cirrhosis - genetics; Liver Cirrhosis - metabolism; Liver Cirrhosis - virology; Microtubules - metabolism; Microtubules - virology; multidisciplinary; Oleic Acid - pharmacology; Phosphatidylinositol Phosphates - metabolism; Proteins; Science; Science (multidisciplinary); Septins - genetics; Septins - metabolism; Virus Replication
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12203

The accumulation of lipid droplets (LD) is frequently observed in hepatitis C virus (HCV) infection and represents an important risk factor for the development of liver steatosis and cirrhosis. The mechanisms of LD biogenesis and growth remain open questions. Here, transcriptome analysis reveals a significant upregulation of septin 9 in HCV-induced cirrhosis compared with the normal liver. HCV infection increases septin 9 expression and induces its assembly into filaments. Septin 9 regulates LD growth and perinuclear accumulation in a manner dependent on dynamic microtubules. The effects of septin 9 on LDs are also dependent on binding to PtdIns5P, which, in turn, controls the formation of septin 9 filaments and its interaction with microtubules. This previously undescribed cooperation between PtdIns5P and septin 9 regulates oleate-induced accumulation of LDs. Overall, our data offer a novel route for LD growth through the involvement of a septin 9/PtdIns5P signalling pathway. The accumulation of lipid droplets is often observed in hepatitis C virus infection, but the mechanism of their formation is not known. Here the authors show that septin 9 expression is increased in infected livers, and a septin 9/phosphatidylinositol 5-phosphate signalling pathway regulates the growth of lipid droplets.