Fitness selection of hyperfusogenic measles virus F proteins associated with neuropathogenic phenotypes.
Nipah virus
fusion
measles virus
mutagenesis
viral encephalitis
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
04 05 2021
04 05 2021
Historique:
entrez:
27
4
2021
pubmed:
28
4
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
Measles virus (MeV) is resurgent and caused >200,000 deaths in 2019. MeV infection can establish a chronic latent infection of the brain that can recrudesce months to years after recovery from the primary infection. Recrudescent MeV leads to fatal subacute sclerosing panencephalitis (SSPE) or measles inclusion body encephalitis (MIBE) as the virus spreads across multiple brain regions. Most clinical isolates of SSPE/MIBE strains show mutations in the fusion (F) gene that result in a hyperfusogenic phenotype in vitro and allow for efficient spread in primary human neurons. Wild-type MeV receptor-binding protein is indispensable for manifesting these mutant F phenotypes, even though neurons lack canonical MeV receptors (CD150/SLAMF1 or nectin-4). How such hyperfusogenic F mutants are selected and whether they confer a fitness advantage for efficient neuronal spread is unresolved. To better understand the fitness landscape that allows for the selection of such hyperfusogenic F mutants, we conducted a screen of ≥3.1 × 10
Identifiants
pubmed: 33903248
pii: 2026027118
doi: 10.1073/pnas.2026027118
pmc: PMC8106313
pii:
doi:
Substances chimiques
Viral Fusion Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI123449
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI115226
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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