Effect of Point Mutations in the Polymerase Genes of the Influenza A/PR/8/34 (H1N1) Virus on the Immune Response in a Mouse Model

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Abstract

The vaccine strains for live attenuated influenza vaccines (LAIVs) have cold-adapted, temperature-sensitive, and attenuated phenotypes, which are guaranteed by the presence of specific mutations from the master donor virus in their internal genes. In this study, we used mutant viruses of the pathogenic A/Puerto Rico/8/34 (H1N1) that contained ts-mutations in PB1 (K265N, V591I), PB2 (V478L), and PA (L28P, V341L) genes along and/or in different combinations to evaluate the impact of these mutations in the immune responses. Sequential addition of tested mutations resulted in the stepwise decrease in virus-specific serum and, to a lesser extent, mucosal antibody levels. We demonstrated strong positive correlation between virus attenuation (virus titer in lung) and antibody titers. The ts-mutations in PB1, PB2, and PA genes are mostly involved in the modulation of the humoral immunity, but also have a moderate effect on the cellular adaptive immune response.

About the authors

S. A. Kuznetsova

Institute of Experimental Medicine, Russian Academy of Medical Sciences

Author for correspondence.
Email: kuznetsova4872@yahoo.co.uk

Svetlana Kuznetsova, candidate of biological Sciences

197376, St. Petersburg

Russian Federation

I. N. Isakova-Sivak

Institute of Experimental Medicine, Russian Academy of Medical Sciences

Email: fake@neicon.ru
197376, St. Petersburg Russian Federation

V. A. Kuznetcova

Institute of Experimental Medicine, Russian Academy of Medical Sciences

Email: fake@neicon.ru
197376, St. Petersburg Russian Federation

G. D. Petukhova

Institute of Experimental Medicine, Russian Academy of Medical Sciences

Email: fake@neicon.ru
197376, St. Petersburg Russian Federation

I. V. Losev

Institute of Experimental Medicine, Russian Academy of Medical Sciences

Email: fake@neicon.ru
197376, St. Petersburg Russian Federation

S. A. Donina

Institute of Experimental Medicine, Russian Academy of Medical Sciences

Email: fake@neicon.ru
197376, St. Petersburg Russian Federation

L. G. Rudenko

Institute of Experimental Medicine, Russian Academy of Medical Sciences

Email: fake@neicon.ru
197376, St. Petersburg Russian Federation

A. N. Naikhin

Institute of Experimental Medicine, Russian Academy of Medical Sciences

Email: fake@neicon.ru
197376, St. Petersburg Russian Federation

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Copyright (c) 2015 Kuznetsova S.A., Isakova-Sivak I.N., Kuznetcova V.A., Petukhova G.D., Losev I.V., Donina S.A., Rudenko L.G., Naikhin A.N.

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