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

Abdellah Akil (1, 2, 3) , Juan Peng (4, 3) , Mohyeddine Omrane (3, 4) , Claire Gondeau (5, 6) , Christophe Desterke (7) , Mickaël Marin (3) , Hélène Tronchère (8) , Cyntia Taveneau (9) , Sokhavuth Sar (3) , Philippe Briolotti (6, 5) , Soumaya Benjelloun (1) , Abdelaziz Benjouad (10, 2) , Patrick Maurel (6, 5) , Valérie Thiers (11) , Stéphane Bressanelli (9) , Didier Samuel (7, 3, 4) , Christian Bréchot (3, 11) , Ama Gassama-Diagne (3, 4)

1 Institut Pasteur du Maroc
2 Laboratoire de biochimie et Immunologie, Faculté des Sciences
3 Physiopathologie et traitement des maladies du foie
4 DHU - Hepatinov
5 Service d'Hépatogastroentérologie
6 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
7 CHB - Centre hépato-biliaire
8 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
9 Virologie Moléculaire et Structurale
10 UIR - Université Internationale de Rabat
11 IP - Institut Pasteur [Paris]

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.

Mots clés: hepatitis-c virus; core protein; diacylglycerol acyltransferase-1; cytoskeleton; biogenesis; metabolism

Mots clés: cell regulation; yeast septin; phosphoinositides; replication

Domaines: Maladies infectieuses; Hépatologie et Gastroentérologie

Abdellah Akil, Juan Peng, Mohyeddine Omrane, Claire Gondeau, Christophe Desterke, et al.. Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV. Nature Communications, 2016, 7, ⟨10.1038/ncomms12203⟩. ⟨hal-01355643⟩