RT Journal Article
SR Electronic
T1 Measles fusion complexes from central nervous system clinical isolates: decreased interaction between hemagglutinin and fusion proteins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.18.449082
DO 10.1101/2021.06.18.449082
A1 Cyrille Mathieu
A1 Tiago Nascimento Figueira
A1 Amanda R. Decker
A1 Marion Ferren
A1 Tiziana F. Bovier
A1 Eric M. Jurgens
A1 Tara C. Marcink
A1 Anne Moscona
A1 Matteo Porotto
YR 2021
UL http://biorxiv.org/content/early/2021/06/19/2021.06.18.449082.abstract
AB 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.