Details

Autor(en) / Beteiligte

• Ajjaji, Dalila
• Ben M'barek, Kalthoum
• Boson, Bertrand
• Omrane, Mohyeddine
• Gassama‐Diagne, Ama
• Blaud, Magali
• Penin, François
• Diaz, Elise
• Ducos, Bertrand
• Cosset, François‐Loïc
• Thiam, Abdou Rachid

Titel

Hepatitis C virus core protein uses triacylglycerols to fold onto the endoplasmic reticulum membrane

Ist Teil von

• Traffic (Copenhagen, Denmark), 2022-01, Vol.23 (1), p.63-80

Ort / Verlag

Former Munksgaard: John Wiley & Sons A/S

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Lipid droplets (LDs) are involved in viral infections, but exactly how remains unclear. Here, we study the hepatitis C virus (HCV) whose core capsid protein binds to LDs but is also involved in the assembly of virions at the endoplasmic reticulum (ER) bilayer. We found that the amphipathic helix‐containing domain of core, D2, senses triglycerides (TGs) rather than LDs per se. In the absence of LDs, D2 can bind to the ER membrane but only if TG molecules are present in the bilayer. Accordingly, the pharmacological inhibition of the diacylglycerol O‐acyltransferase enzymes, mediating TG synthesis in the ER, inhibits D2 association with the bilayer. We found that TG molecules enable D2 to fold into alpha helices. Sequence analysis reveals that D2 resembles the apoE lipid‐binding region. Our data support that TG in LDs promotes the folding of core, which subsequently relocalizes to contiguous ER regions. During this motion, core may carry TG molecules to these regions where HCV lipoviroparticles likely assemble. Consistent with this model, the inhibition of Arf1/COPI, which decreases LD surface accessibility to proteins and ER‐LD material exchange, severely impedes the assembly of virions. Altogether, our data uncover a critical function of TG in the folding of core and HCV replication and reveals, more broadly, how TG accumulation in the ER may provoke the binding of soluble amphipathic helix‐containing proteins to the ER bilayer. Core amphipathic helix domain, D2, cannot fold onto the ER, unless triacylglycerols are present. Triglyceride accumulation in the ER might recruit amphipathic proteins. D2 has similarities with the apoE lipid binding region, suggesting that it might have an affinity for triacylglycerols. In the absence of LDs or triacylglycerols, Core is degraded. Core binding to LDs, where triacylglycerols are more accessible, prevents Core degradation. Core may relocalize from the LD surface to the ER regions enriched with triacylglycerols where virions assemble.