The neuraminidases of MDCK grown human influenza A(H3N2) viruses isolated since 1994 can demonstrate receptor binding

Virology Journal

Jennifer L McKimm-Breschkin²  Yi-Mo Deng¹  Peter G Mohr³ 

[1] WHO Collaborating Centre for Reference and Research on Influenza, 792 Elizabeth Street, Melbourne 3000, VIC, Australia;CSIRO Manufacturing, 343 Royal Parade, Parkville 3052, VIC, Australia;CSIRO Australian Animal Health Laboratory, Portarlington Road, Geelong 3219, VIC, Australia

关键词: Influenza;    Receptor binding;    Zanamivir;    Oseltamivir;    Neuraminidase inhibitors;    Neuraminidase;   

Others  :  1224946
DOI  :  10.1186/s12985-015-0295-3

 received in 2014-12-23, accepted in 2015-04-04,  发布年份 2015

【 摘 要 】

Background

The neuraminidases (NAs) of MDCK passaged human influenza A(H3N2) strains isolated since 2005 are reported to have dual functions of cleavage of sialic acid and receptor binding. NA agglutination of red blood cells (RBCs) can be inhibited by neuraminidase inhibitors (NAIs), thus distinguishing it from haemagglutinin (HA) binding. We wanted to know if viruses prior to 2005 can demonstrate this property.

Methods

Pairs of influenza A(H3N2) isolates ranging from 1993–2008 passaged in parallel only in eggs or in MDCK cells were tested for inhibition of haemagglutination by various NAIs.

Results

Only viruses isolated since 1994 and cultured in MDCK cells bound chicken RBCs solely through their NA. NAI inhibition of agglutination of turkey RBCs was seen for some, but not all of these same MDCK grown viruses. Efficacy of inhibition of enzyme activity and haemagglutination differed between NAIs. For many viruses lower concentrations of oseltamivir could inhibit agglutination compared to zanamivir, although they could both inhibit enzyme activity at comparable concentrations. An E119V mutation reduced sensitivity to oseltamivir and 4-aminoDANA for both the enzyme assay and inhibition of agglutination. Sequence analysis of the NAs and HAs of some paired viruses revealed mutations in the haemagglutinin of all egg passaged viruses. For many of the paired egg and MDCK cultured viruses we found no differences in their NA sequences by Sanger sequencing. However, deep sequencing of MDCK grown isolates revealed low levels of variant populations with mutations at either D151 or T148 in the NA, suggesting mutations at either site may be able to confer this property.

Conclusions

The NA active site of MDCK cultured human influenza A(H3N2) viruses isolated since 1994 can express dual enzyme and receptor binding functions. Binding correlated with either D151 or T148 mutations. The catalytic and receptor binding sites do not appear to be structurally identical since relative concentrations of the NAIs to inhibit enzyme activity and agglutination differ.

【 授权许可】

   
2015 Mohr et al.; licensee BioMed Central.

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