Using a mouse-adapted A/HK/01/68 influenza virus to analyse the impact of NS1 evolution in codons 196 and 231 on viral replication and virulence.

Eiden, Sebastian; Dijkman, Ronald; Zell, Roland; Fuchs, Jonas; Kochs, Georg (2020). Using a mouse-adapted A/HK/01/68 influenza virus to analyse the impact of NS1 evolution in codons 196 and 231 on viral replication and virulence. Journal of general virology, 101(6), pp. 587-598. Society for General Microbiology 10.1099/jgv.0.001422

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Seasonal influenza viruses circulating between 1918 and 2009 harboured two prevalent genetic variations in the NS1 coding region. A glutamic acid (E)-to-lysine (K) exchange at position 196 was reported to diminish the capacity of NS1 to control interferon induction. Furthermore, alterations at position 231 determine a carboxy-terminal extension of seven amino acids from 230 to 237 residues. Sequence analyses of NS1 of the last 90 years suggest that variations at these two positions are functionally linked. To determine the impact of the two positions on viral replication in vivo, we used a mouse-adapted variant of A/Hong Kong/01/68 (maHK68) (H3N2). maHK68 encodes an NS1 of 237 amino acids with lysine at position 196. A panel of recombinant maHK68 viruses was generated encoding NS1 variants that differed at positions 196 and 231. Our analyses showed a clear effect of the K-196-to-E exchange on interferon induction and virus virulence. These effects were further modulated by the loss of the seven-amino-acid extension. We propose that the combination of NS1 E-196 with the short C-terminal variant conferred a fitness advantage that is reflected by increased virulence in vivo. Notably, this particular NS1 constellation was observed for the pandemic 1918 H1N1 virus.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology

UniBE Contributor:

Dijkman, Ronald

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

0022-1317

Publisher:

Society for General Microbiology

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

30 Jul 2020 09:33

Last Modified:

30 Jul 2020 09:33

Publisher DOI:

10.1099/jgv.0.001422

PubMed ID:

32416749

Uncontrolled Keywords:

NS1 evolution influenza A virus mouse-adapted A/HK/1/68 non-structural protein 1 orthomyxoviruses viral interferon antagonist

BORIS DOI:

10.7892/boris.145429

URI:

https://boris.unibe.ch/id/eprint/145429

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