Mutations in the Neuraminidase-Like Protein of Bat Influenza H18N11 Virus Enhance Virus Replication in Mammalian Cells, Mice, and Ferrets.
Animals
Cell Line
Chiroptera
/ virology
Disease Models, Animal
Female
Ferrets
/ virology
Lung
/ virology
Mice
Mice, Inbred BALB C
Models, Molecular
Mutation
Neuraminidase
/ chemistry
Orthomyxoviridae
/ enzymology
Orthomyxoviridae Infections
/ veterinary
Trachea
/ virology
Virus Replication
/ physiology
Zoonoses
/ virology
H18N11
NA
bat influenza
replication
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
14 02 2020
14 02 2020
Historique:
received:
30
08
2019
accepted:
25
11
2019
pubmed:
6
12
2019
medline:
22
8
2020
entrez:
6
12
2019
Statut:
epublish
Résumé
To characterize bat influenza H18N11 virus, we propagated a reverse genetics-generated H18N11 virus in Madin-Darby canine kidney subclone II cells and detected two mammal-adapting mutations in the neuraminidase (NA)-like protein (NA-F144C and NA-T342A, N2 numbering) that increased the virus titers in three mammalian cell lines (i.e., Madin-Darby canine kidney, Madin-Darby canine kidney subclone II, and human lung adenocarcinoma [Calu-3] cells). In mice, wild-type H18N11 virus replicated only in the lungs of the infected animals, whereas the NA-T342A and NA-F144C/T342A mutant viruses were detected in the nasal turbinates, in addition to the lungs. Bat influenza viruses have not been tested for their virulence or organ tropism in ferrets. We detected wild-type and single mutant viruses each possessing NA-F144C or NA-T342A in the nasal turbinates of one or several infected ferrets, respectively. A mutant virus possessing both the NA-F144C and NA-T342A mutations was isolated from both the lung and the trachea, suggesting that it has a broader organ tropism than the wild-type virus. However, none of the H18N11 viruses caused symptoms in mice or ferrets. The NA-F144C/T342A double mutation did not substantially affect virion morphology or the release of virions from cells. Collectively, our data demonstrate that the propagation of bat influenza H18N11 virus in mammalian cells can result in mammal-adapting mutations that may increase the replicative ability and/or organ tropism of the virus; overall, however, these viruses did not replicate to high titers throughout the respiratory tract of mice and ferrets.
Identifiants
pubmed: 31801857
pii: JVI.01416-19
doi: 10.1128/JVI.01416-19
pmc: PMC7022354
pii:
doi:
Substances chimiques
Neuraminidase
EC 3.2.1.18
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 : HHSN272201400008C
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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