Adaptive mutations of neuraminidase stalk truncation and deglycosylationconfer enhanced pathogenicity of influenza A viruses

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/474301.do
DOI
10.1038/s41598-017-11348-0
Title
Adaptive mutations of neuraminidase stalk truncation and deglycosylationconfer enhanced pathogenicity of influenza A viruses
Description
This study was supported by grants from the Korea Healthcare TechnologyR&D Project of the Ministry of Health and Welfare (grant number:A103001) and the Korea Health Technology R&D Project through the KoreaHealth Industry Development Institute, funded by the Ministry of Health& Welfare, Republic of Korea (grant number: HI16C0976). The funders hadno role in study design, data collection and analysis, decision topublish, or preparation of the manuscript.
abstract
It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry. We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice. The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region. To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics. Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice. The increased pathogenicity of these NA stalk mutants was also reproduced in ferrets. In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model. Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
provenance
Made available in Cube on 2018-09-28T10:42:25Z (GMT). No. of bitstreams: 0
language
English
author
Park, Sehee
Il Kim, Jin
Lee, Ilseob
Bae, Joon-Yong
Yoo, Kirim
Nam, Misun
Kim, Juwon
Park, Mee Sook
Song, Ki-Joon
Song, Jin-Won
Kee, Sun-Ho
Park, Man-Seong
accessioned
2018-09-28T10:42:25Z
available
2018-09-28T10:42:25Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/474301.do
Funder
보건복지부
Funding Program
감염병위기대응기술개발(구.면역백신개발)
Project ID
1465012531
Jurisdiction
Rep.of Korea
Project Name
Study on inhibition of antiviral-resistance mechanism and evaluation of combination therapy for influenza
rights
openAccess
type
article


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