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
| Autor: | Roland Zell, Ronald Dijkman, Georg Kochs, Jonas Fuchs, Sebastian Eiden |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
viruses
Virulence Biology Viral Nonstructural Proteins medicine.disease_cause Virus Replication Virus Cell Line Madin Darby Canine Kidney Cells Evolution Molecular 03 medical and health sciences Mice Dogs Orthomyxoviridae Infections Interferon Virology Cell Line Tumor Genetic variation Influenza Human medicine Influenza A virus Coding region Animals Humans Amino Acids 610 Medicine & health Codon 030304 developmental biology chemistry.chemical_classification 0303 health sciences Mice Inbred BALB C 630 Agriculture 030302 biochemistry & molecular biology virus diseases Amino acid Mice Inbred C57BL HEK293 Cells chemistry Viral replication A549 Cells Host-Pathogen Interactions 570 Life sciences biology medicine.drug |
| Zdroj: | The Journal of general virology. 101(6) |
| ISSN: | 1465-2099 |
| Popis: | 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 replicationin 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 virulencein vivo. Notably, this particular NS1 constellation was observed for the pandemic 1918 H1N1 virus. |
| Databáze: | OpenAIRE |
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