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Molecular and biochemical characterization of the NS1 protein of non-cultured influenza B virus strains circulating in Singapore

tetano

Editor, Senior Moderator
Microb Genom. 2016 Aug 25;2(8):e000082. doi: 10.1099/mgen.0.000082. eCollection 2016.
[h=1]Molecular and biochemical characterization of the NS1 protein of non-cultured influenza B virus strains circulating in Singapore.[/h] Jumat MR[SUP]1[/SUP], Wong P[SUP]2[/SUP], Lee RT[SUP]3[/SUP], Maurer-Stroh S[SUP]4[/SUP], Tan BH[SUP]2[/SUP], Sugrue RJ[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP[SUB]92-93[/SUB]), and that p23 contained the first 92 amino acids of the NS1 protein. Sequence analysis of the Singapore strains indicated the presence of either DP[SUB]92-93[/SUB] or NP[SUB]92-93[/SUB] in the NS1 protein, but protein expression analysis showed that p23 was only detected in NS1 proteins with DP[SUB]92-93.[/SUB]. An additional adjacent proline residue at position 94 (P[SUB]94[/SUB]) was present in some strains and correlated with increased p23 levels, suggesting that P[SUB]94[/SUB] has a synergistic effect on the cleavage of the NS1 protein. The first 145 amino acids of the NS1 protein are required for inhibition of ISG15-mediated ubiquitination, and our analysis showed that Influenza B viruses circulating in Singapore with DP[SUB]92-93[/SUB] expressed truncated NS1 proteins and may differ in their capacity to inhibit ISG15 activity. Thus, DP[SUB]92-93[/SUB] in the NS1 protein may confer a disadvantage to Influenza B viruses circulating in the human population and interestingly the low frequency of DP[SUB]92-93[/SUB]detection in the NS1 protein since 2004 is consistent with this suggestion.


[h=4]KEYWORDS:[/h] B/Lee/40; Cleavage; Influenza B; NS1; Proteolysis

PMID: 28348873 PMCID: PMC5320597 DOI: 10.1099/mgen.0.000082
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