Contribution of Neuraminidase of Influenza Viruses to the Sensitivity to Sera Inhibitors and Reassortment Efficiency



Irina Kiseleva^, *, Natalie Larionova^, Ekaterina Fedorova, Ekaterina Bazhenova, Irina Dubrovina, Irina Isakova-Sivak , Larisa Rudenko
Department of Virology, Institute of Experimental Medicine, St. Petersburg, Russia


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© Kiseleva et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Institute of Experimental Medicine, 12 Acad. Pavlov Street, St. Petersburg, Russia 197376; Tel: +7 (812) 234 6860; Fax: +7(812)2349489; E-mail: irina.v.kiseleva@gmail.com
^ These authors contributed equally to this work.


Abstract

Live attenuated influenza vaccine (LAIV) represent reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments inherited from circulating wild-type (WT) parental influenza viruses recommended for inclusion into seasonal vaccine formulation, and the 6 internal protein-encoding gene segments from cold-adapted attenuated master donor viruses (genome composition 6:2). In this study, we describe the obstacles in developing LAIV strains while taking into account the phenotypic peculiarities of WT viruses used for reassortment. Genomic composition analysis of 849 seasonal LAIV reassortants revealed that over 80% of reassortants based on inhibitor-resistant WT viruses inherited WT NA, compared to 26% of LAIV reassortants based on inhibitor-sensitive WT viruses. In addition, the highest percentage of LAIV genotype reassortants was achieved when WT parental viruses were resistant to non-specific serum inhibitors. We demonstrate that NA may play a role in influenza virus sensitivity to non-specific serum inhibitors. Replacing NA of inhibitor-sensitive WT virus with the NA of inhibitor-resistant master donor virus significantly decreased the sensitivity of the resulting reassortant virus to serum heat-stable inhibitors.

Keywords: Influenza virus, live influenza vaccine, neuraminidase, normal serum inhibitors, reassortment.