TY - JOUR

T1 - Contribution of neuraminidase of influenza viruses to the sensitivity to serum inhibitors and reassortment efficiency

AU - Kiseleva, I. V.

AU - Larionova, N. V.

AU - Bazhenova, E. A.

AU - Fedorova, E. A.

AU - Dubrovina, I. A.

AU - Isakova-Sivak, I. N.

AU - Rudenko, L. G.

N1 - Funding Information: ACKNOWLEDGMENTS This work was partially supported by the Program for Appropriate Technologies in Health (PATH), Washington, United States. Publisher Copyright: © 2014 Allerton Press, Inc. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.

PY - 2014/7/1

Y1 - 2014/7/1

N2 - Live attenuated influenza vaccine (LAIV) consists of reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments inherited from the circulating wild-type (WT) parental viruses and six internal protein-encoding gene segments from cold-adapted attenuated master donor viruses (genome composition 6: 2). In this study, we describe the difficulties in development of LAIV strains depending on the phenotypic peculiarities of the WT viruses used for reassortment. Genomic-composition analysis of 849 reassortants revealed that over 80% of reassortants based on the inhibitor-resistant WT viruses inherited WT NA as compared to 26% of reassortants based on the inhibitor-sensitive WT viruses. In addition, the highest percentage of vaccine genotype reassortants was achieved when WT parental viruses were resistant to nonspecific serum inhibitors. We show that NA may play a role in the influenza virus' sensitivity to a nonspecific serum inhibitors. Replacing the NA of the inhibitor-sensitive WT virus with the NA of the inhibitor-resistant master donor virus significantly decreased the sensitivity of the resulting reassortant virus to nonspecific inhibitors.

AB - Live attenuated influenza vaccine (LAIV) consists of reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments inherited from the circulating wild-type (WT) parental viruses and six internal protein-encoding gene segments from cold-adapted attenuated master donor viruses (genome composition 6: 2). In this study, we describe the difficulties in development of LAIV strains depending on the phenotypic peculiarities of the WT viruses used for reassortment. Genomic-composition analysis of 849 reassortants revealed that over 80% of reassortants based on the inhibitor-resistant WT viruses inherited WT NA as compared to 26% of reassortants based on the inhibitor-sensitive WT viruses. In addition, the highest percentage of vaccine genotype reassortants was achieved when WT parental viruses were resistant to nonspecific serum inhibitors. We show that NA may play a role in the influenza virus' sensitivity to a nonspecific serum inhibitors. Replacing the NA of the inhibitor-sensitive WT virus with the NA of the inhibitor-resistant master donor virus significantly decreased the sensitivity of the resulting reassortant virus to nonspecific inhibitors.

KW - influenza virus

KW - live attenuated influenza vaccine

KW - neuraminidase

KW - reassortment

KW - serum inhibitors

UR - http://www.scopus.com/inward/record.url?scp=84907507410&partnerID=8YFLogxK

U2 - 10.3103/S0891416814030045

DO - 10.3103/S0891416814030045

M3 - Article

C2 - 25335411

AN - SCOPUS:84908499768

VL - 29

SP - 130

EP - 138

JO - Molecular Genetics, Microbiology and Virology

JF - Molecular Genetics, Microbiology and Virology

SN - 0891-4168

IS - 3

ER -