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Measles fusion complexes from central nervous system clinical isolates: decreased interaction between hemagglutinin and fusion proteins

Abstract : Abstract Measles virus (MeV) viral entry is mediated by a fusion complex comprised of a receptor binding protein (hemagglutinin, H) and a fusion protein (F). The wild type H/F complex requires interaction with specific proteinaceous receptors (CD150/SLAM and nectin-4) in order to be activated. In contrast the H/F complexes isolated from viruses infecting the central nervous system (CNS) do not require a specific receptor. A single amino acid change in the F protein (L454W) was previously identified in two patients with lethal sequelae of MeV CNS infection, and the F bearing this mutation mediates fusion even without the H protein. We show here that viruses bearing the L454W fusion complex are less efficient than wt virus at targeting receptor expressing cells and that this defect is associated with a decreased interaction between the H and the F proteins. Importance Measles (Mev) infection can cause serious complications including measles inclusion body encephalitis (MIBE) and subacute sclerosing panencephalitis (SSPE). MIBE and SSPE are relatively rare but lethal. We have shown that the fusion complex of CNS adapted clinical samples can spread in the absence of known receptor. We now provide evidence that HRC mutations leading to CNS adaptation come at a cost to the efficiency of viral entry. One Sentence Summary Measles CNS adapted fusion complexes have altered H/F interaction.
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Preprints, Working Papers, ...
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https://hal.archives-ouvertes.fr/hal-03430034
Contributor : Cyrille Mathieu Connect in order to contact the contributor
Submitted on : Wednesday, November 17, 2021 - 1:54:20 PM
Last modification on : Friday, November 19, 2021 - 2:22:24 PM
Long-term archiving on: : Friday, February 18, 2022 - 7:56:34 PM

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Cyrille Mathieu, Tiago Nascimento Figueira, Amanda Decker, Marion Ferren, Tiziana Bovier, et al.. Measles fusion complexes from central nervous system clinical isolates: decreased interaction between hemagglutinin and fusion proteins. 2021. ⟨hal-03430034⟩

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