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Attenuation of A/chicken/Kurgan/3/2005 (H5N1) influenza virus using selection in an environment simulating the life cycle of wild duck viruses

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Abstract

The highly pathogenic A/chicken/Kurgan/3/2005, (K/05) H5N1 influenza virus was attenuated using selection in an environment simulating the life cycle of wild duck influenza viruses. The goal of this work was the selection of viruses which are more stable for protease cleavage and low pH than the parent virus. The attenuated virus (K/at) was nonpathogenic for mice and did not induce mortality in embryonated chicken eggs. The pH of K/at hemagglutinin conformational change decreased by 0.45–0.50 units compared with the initial K/05 virus. K/at increased the affinity for fucosylated receptors in contrast to K/05. The total sequencing and analysis of the viral genome identified ten amino acid substitutions (1 in PB2, PB1, NP, and NS1; 2 in NA; and 4 in HA) in K/at relative to the initial K/05 located in functionally important regions. K/at substitutions Asp54Asn in HA1 and Val48Ile in HA2 in hemagglutinine are the reverses to the sequence characteristic of wild duck viruses. These substitutions, like the substitution Lys131Thr in HA2, change the mobility of molecules and can influence the parameters of conformation transition of hemagglutinin. The fourth substitution in HA1 Lys222Thr was located in the region of interaction with the receptor. Substitutions in NS1 (Arg37His) and PB1 (Leu218Met) were identified in the region of nuclear localization signal, and mutations in proteins PB2 (Asp256Asn) and NP (Trp386Cys) were located at sites involved in the transcription and replication of the viral genome.

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Authors and Affiliations

  1. Chumakov Institute of Poliomyelitis and Viral Encephalitis, Russian Academy of Medical Sciences, Moscow oblast, 142782, Russia

    N. F. Lomakina, E. Yu. Boravleva, E. A. Kropotkina & A. S. Gambaryan

  2. Kovalenko All-Russia Research Institute of Experimental Veterinary Medicine, Russian Academy of Agricultural Sciences, Ryazanskii prospect 24/1, Moscow, 109428, Russia

    N. F. Lomakina

  3. Ivanovskii Institute of Virology, ul. Gamalei 16, Moscow, Russia

    S. S. Yamnikova

  4. Federal Center for Animal Health, Vladimir, 600901, Russia

    V. V. Drygin

Authors
  1. N. F. Lomakina
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  2. E. Yu. Boravleva
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  3. E. A. Kropotkina
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  4. S. S. Yamnikova
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  5. V. V. Drygin
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  6. A. S. Gambaryan
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Additional information

Original Russian Text © N.F. Lomakina, E.Yu. Boravleva, E.A. Kropotkina, S.S. Yamnikova, V.V. Drygin, A.S. Gambaryan, 2011, published in Molekulyarnaya Genetika, Mikrobiologiya i Virusologiya, 2011, No. 3, pp. 35–41.

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Lomakina, N.F., Boravleva, E.Y., Kropotkina, E.A. et al. Attenuation of A/chicken/Kurgan/3/2005 (H5N1) influenza virus using selection in an environment simulating the life cycle of wild duck viruses. Mol. Genet. Microbiol. Virol. 26, 132–139 (2011). https://doi.org/10.3103/S0891416811030025

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  • DOI: https://doi.org/10.3103/S0891416811030025

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