HA-Dependent Tropism of H5N1 and H7N9 Influenza Viruses to Human Endothelial Cells Is Determined by Reduced Stability of the HA, Which Allows the Virus To Cope with Inefficient Endosomal Acidification and Constitutively Expressed IFITM3.
Amino Acid Substitution
Animals
Dogs
Endosomes
/ metabolism
Endothelial Cells
/ metabolism
Gene Expression Regulation
Hemagglutinin Glycoproteins, Influenza Virus
/ chemistry
Host-Pathogen Interactions
/ genetics
Humans
Hydrogen-Ion Concentration
Influenza A Virus, H5N1 Subtype
/ genetics
Influenza A Virus, H7N9 Subtype
/ genetics
Lung
/ metabolism
Madin Darby Canine Kidney Cells
Membrane Proteins
/ genetics
Models, Molecular
Mutation
Protein Binding
Protein Conformation
RNA-Binding Proteins
/ genetics
Reassortant Viruses
/ genetics
Structure-Activity Relationship
Viral Tropism
/ genetics
Virus Replication
IFITM
endothelial
fusion
hemagglutinin
influenza
stability
tropism
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
12 12 2019
12 12 2019
Historique:
received:
23
07
2019
accepted:
30
09
2019
pubmed:
11
10
2019
medline:
12
6
2020
entrez:
11
10
2019
Statut:
epublish
Résumé
Previous studies revealed that certain avian influenza A viruses (IAVs), including zoonotic H5N1 and H7N9 IAVs, infect cultured human lung microvascular endothelial cells (HULEC) more efficiently than other IAVs and that tropism to HULEC is determined by viral hemagglutinin (HA). To characterize mechanisms of HA-mediated endotheliotropism, we used 2:6 recombinant IAVs harboring HAs from distinctive avian and human viruses and found that efficient infection of HULEC correlated with low conformational stability of the HA. We next studied effects on viral infectivity of single-point amino acid substitutions in the HA of 2:6 recombinant virus A/Vietnam/1203/2004-PR8 (H5N1). Substitutions H8Q, H103Y, T315I, and K58
Identifiants
pubmed: 31597765
pii: JVI.01223-19
doi: 10.1128/JVI.01223-19
pmc: PMC6912096
pii:
doi:
Substances chimiques
Hemagglutinin Glycoproteins, Influenza Virus
0
IFITM3 protein, human
0
Membrane Proteins
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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