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Co-option of membrane wounding enables virus penetration into cells.

Cell Host Microbe 18, 75-85 (2015)
Open Access Green as soon as Postprint is submitted to ZB.
During cell entry, non-enveloped viruses undergo partial uncoating to expose membrane lytic proteins for gaining access to the cytoplasm. We report that adenovirus uses membrane piercing to induce and hijack cellular wound removal processes that facilitate further membrane disruption and infection. Incoming adenovirus stimulates calcium influx and lysosomal exocytosis, a membrane repair mechanism resulting in release of acid sphingomyelinase (ASMase) and degradation of sphingomyelin to ceramide lipids in the plasma membrane. Lysosomal exocytosis is triggered by small plasma membrane lesions induced by the viral membrane lytic protein-VI, which is exposed upon mechanical cues from virus receptors, followed by virus endocytosis into leaky endosomes. Chemical inhibition or RNA interference of ASMase slows virus endocytosis, inhibits virus escape to the cytosol, and reduces infection. Ceramide enhances binding of protein-VI to lipid membranes and protein-VI-induced membrane rupture. Thus, adenovirus uses a positive feedback loop between virus uncoating and lipid signaling for efficient membrane penetration.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Human Epithelial-cells; Plasma-membrane; Acid Sphingomyelinase; Adenovirus Type-2; Cystic-fibrosis; Repair; Entry; Endocytosis; Inhibition; Infection
Reviewing status
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)