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Co-option of membrane wounding enables virus penetration into cells

Luisoni, Stefania and Suomalainen, Maarit and Boucke, Karin and Tanner, Lukas B. and Wenk, Markus R. and Guan, Xue Li and Grzybek, Michał and Coskun, Ünal and Greber, Urs F.. (2015) Co-option of membrane wounding enables virus penetration into cells. Cell host & microbe, Vol. 18, H. 1. pp. 75-85.

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Official URL: http://edoc.unibas.ch/dok/A6411213

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Abstract

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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Tuberculosis Research (Gagneux)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Wenk, Markus and Guan, Xueli
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:1931-3128
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Sep 2015 14:30
Deposited On:04 Sep 2015 14:30

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