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The Spatial Location of Single Amino Acid Substitutions in Proteins of Cold-Adapted Influenza B Viruses and Their Impact upon Cold Adaptation

  • E. A. StepanovaEmail author
  • E. V. Krutikova
  • I. V. Kiseleva
  • L. G. Rudenko
REVIEWS

Abstract

This review summarizes the locations of unique amino acid substitutions in proteins of cold-adapted influenza B viruses, master donor viruses of live attenuated influenza vaccines: B/Ann Arbor/1/66ca, B/USSR/60/69, B/Leningrad/14/17/55, B/Victoria/2/63/87, and B/Vienna/1/99ca. The analysis is based on data on the viral sequences and information on the functional organization of internal proteins of the influenza B virus. A description is given of the main features of the structure of internal proteins from influenza B virus and a recent understanding of the functioning of their domains. We describe 35 substitutions in proteins of the ribonucleoprotein complex [PB1 (3), PB2 (10), PA (11), NP (11)] of cold-adapted influenza B viruses. In total, there are 44 amino acid positions that are considered to be associated with cold adaptation. Protein domains involved in protein–protein interactions are the most susceptible to changes. In the polymerase complex, the largest number of replacements were found in C-terminal domains of PA and PB2 proteins, forming the external parts of the polymerase complex structure and providing interaction among subunits, with cellular factors, and with the nucleoprotein (NP). Substitutions in the NP are located in the areas responsible for its oligomerization (flexible N-terminal fragment), as well as for interaction with the polymerase complex (the outer surface of the NP head and body domains). All the cold-adapted viruses had changes in the seventh segment of the genome, leading to amino acid substitutions in the matrix protein or BM2 proton channel. An analysis of the location of amino acid substitutions allows it to be theorized that an important role is played by the internal gene constellation in attenuation of cold-adapted viruses.

Keywords:

review influenza B virus cold adaptation temperature sensitivity attenuation 

Notes

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Copyright information

© Allerton Press, Inc. 2018

Authors and Affiliations

  • E. A. Stepanova
    • 1
    Email author
  • E. V. Krutikova
    • 1
  • I. V. Kiseleva
    • 1
    • 2
  • L. G. Rudenko
    • 1
  1. 1.Institute of Experimental Medicine, St. PetersburgRussia
  2. 2.St. Petersburg State UniversitySt. PetersburgRussia

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