A GENETIC ANALYSIS OF A H1N1 PANDEMIC INFLUENZA VIRUS IN THE COURSE OF THE EPIDEMIC

  • Authors: Kostryukova ES1, Zakharzhevskaya NB1, Kostin PA1, Ilyina EN1, Larin AK1, Gribanov OG1, Selezneva OV1, Prikhodko EA1, Akopian TA1, Generozov EV1, Lazarev VN1,2, Levitsky SA1,2, Kondratov IG1, Alekseev DG1, Bazaleev NA1, Klimova EA3, Esaulova MR3, Yuschuk ND3, Govorun VM1,2,4, Sergienko VI1
  • Affiliations:
    1. Research Institute of Physicochemical Medicine
    2. Institute of Bioorganic Chemistry of the Russian Academy of Sciences
    3. Moscow State Medical Stomatological University
    4. Russian Research Center "Kurchatov Institute"
  • Issue: Vol 84, No 3 (2012)
  • Pages: 48-54
  • Section: Articles
  • URL: https://ter-arkhiv.ru/0040-3660/article/view/31010
  • Cite item

Abstract


Aim. To assess genetic variability of A H1N1 pan influenza virus (IV) in the course of the epidemic and to detect a set of human nucleotide polymorphisms responsible for a severe course of the disease. Material and methods. Extraction and purification ofviral genomic RNA from the nasopharyngeal smears and genomic human DNA from the leukocytic fraction of venous blood was made in 230 patients from Moscow, Moscow and Sverdlovsk Regions with severe acute respiratory virus infection (ARVI). A flu virus type was established in amplification reaction with on-line detection of the products with application of primers recommended by WHO. Genetic polymorphisms of A H1N1 pan IV and human genes were determined with minisequencing reaction followed by detection of the products of MALDI-time-of-flight mass-spectrometry. Nucleotide sequences of the complete genome were revealed for 15 isolates of A H1N1 pan IV. Results. A H1N1 IV was identified in 77 cases (46 were pandemic, 31 seasonal). Mutations causing genetically determined resistance to adamants (amantadin, rimantadin) were detected in all 46 samples of genomic RNA of A H1N1 pan IV. Mutation leading to oseltamivir (tamiflu) resistance was found in one sample. It is shown that a severe course of A H1N1 pan IV infection is associated with genotypes predisposing to development of thromboses, bronchopulmonary diseases and hypertention. Genetic tests for prognosis of a complicated course of the flu are proposed. The revealed full-genome sequences of the segments of genomic RNA of 15 A H1N1 pan influenza viruses are deposited in GenBank. Conclusion. We are the first in Russia to detect a mutant variant of A H1N1 pan IV resistant to oseltamivir. We describe a set of nucleotide polymorphisms which determine a complicated course of the flu in patients with identified A H1N1 pan IV.

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About the authors

E S Kostryukova

Research Institute of Physicochemical Medicine

Email: el-es@yandex.ru

N B Zakharzhevskaya

Research Institute of Physicochemical Medicine

P A Kostin

Research Institute of Physicochemical Medicine

E N Ilyina

Research Institute of Physicochemical Medicine

A K Larin

Research Institute of Physicochemical Medicine

O G Gribanov

Research Institute of Physicochemical Medicine

O V Selezneva

Research Institute of Physicochemical Medicine

E A Prikhodko

Research Institute of Physicochemical Medicine

T A Akopian

Research Institute of Physicochemical Medicine

E V Generozov

Research Institute of Physicochemical Medicine

V N Lazarev

Research Institute of Physicochemical Medicine; Institute of Bioorganic Chemistry of the Russian Academy of Sciences

S A Levitsky

Research Institute of Physicochemical Medicine; Institute of Bioorganic Chemistry of the Russian Academy of Sciences

I G Kondratov

Research Institute of Physicochemical Medicine

D G Alekseev

Research Institute of Physicochemical Medicine

N A Bazaleev

Research Institute of Physicochemical Medicine

E A Klimova

Moscow State Medical Stomatological University

M R Esaulova

Moscow State Medical Stomatological University

N D Yuschuk

Moscow State Medical Stomatological University

V M Govorun

Research Institute of Physicochemical Medicine; Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Russian Research Center "Kurchatov Institute"

V I Sergienko

Research Institute of Physicochemical Medicine

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