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Axl can serve as entry factor for lassa virus depending on the functional glycosylation of dystroglycan
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2018 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 92, no 5, article id e01613-17Article in journal (Refereed) Published
Abstract [en]

The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa. Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism. The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear. Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification. We found that in the absence of functional DG, Axl can mediate LASV entry via apoptotic mimicry. Productive entry requires virus-induced receptor activation, involves macropinocytosis, and critically depends on LAMP-1. In endothelial cells that express low levels of glycosylated DG, both receptors can promote LASV entry. In sum, our study defines the roles of Axl in LASV entry and provides a rationale for targeting Axl in antiviral therapy.

Place, publisher, year, edition, pages
2018. Vol. 92, no 5, article id e01613-17
Keywords [en]
Axl, Lassa virus, attachment, dystroglycan, entry factor, macropinocytosis, receptor, viral entry
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:umu:diva-148138DOI: 10.1128/JVI.01613-17ISI: 000424744800005PubMedID: 29237830OAI: oai:DiVA.org:umu-148138DiVA, id: diva2:1210726
Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-10-29Bibliographically approved

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Gerold, Gisa

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  • nn-NB
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