Email this article MECHANISMS OF ATTENUATION OF COLD-ADAPTED STRAIN A/KRASNODAR/101/35/59 (H2N2)
- Authors: Markushin S.G.1, Svitich O.A.1, Kinkulkina A.R.1, Koptyaeva I.B.1, Lisovskaya K.V.1
-
Affiliations:
- Mechnikov Research Institute of Vaccines and Sera
- Issue: Vol 93, No 2 (2016)
- Pages: 49-56
- Section: ORIGINAL RESEARCHES
- Submitted: 10.04.2019
- Published: 28.04.2016
- URL: https://microbiol.crie.ru/jour/article/view/30
- DOI: https://doi.org/10.36233/0372-9311-2016-2-49-56
- ID: 30
Cite item
Full Text
Abstract
Aim. Study of mechanisms of attenuation of cold-adapted (ca) influenza virus strain A/ Krasnodar/101/35/59 (H2N2), associated with disruption of NS1 protein functions. Materials and methods. Study of interferonogenic activity of ca strain A/Krasnodar/101/35/59 (H2N2), its parent variant A/Krasnodar/101/59 (H2N2), virulent strain A/WSN/33 (H1N1) and a number of single gene and multiple gene reassortants between these strains, obtained using reverse genetics, was carried out. Study of dynamics of IFNp gene expression was carried out by using a methodical approach of RT-PCR in real time mode. Results. Inclusion of PB-1 gene of ca strain A/ Krasnodar/101/35/59 (H2N2) with reversion to wild type into genome composition of virulent strain А/WSN/33 (H1N1) does not result in a sharp change of interferonogenic activity of the reassortant. At the same time, similar inclusion of PB-1 gene of ca strain resulted in an incredible growth of interferonogenic activity of the reassortant. On the other hand, inclusion of NP-gene of wild type strain A/Krasnodar/101/59 (H2N2) into genome composition of the wild type strain А/WSN/33 did not differ by effect on interferonogenicity of the reassortant from inclusion of NP-gene of ca strain. Conclusion. Both constellations of genes of parent variants and mutations localized in these genes could affect formation of attenuation phenotype of reassortants. The data obtained allow to assume possible mechanisms of attenuation of ca strains, associated with disruption of NS gene function.
About the authors
S. G. Markushin
Mechnikov Research Institute of Vaccines and Sera
Author for correspondence.
Email: noemail@neicon.ru
Россия
O. A. Svitich
Mechnikov Research Institute of Vaccines and Sera
Email: noemail@neicon.ru
Россия
A. R. Kinkulkina
Mechnikov Research Institute of Vaccines and Sera
Email: noemail@neicon.ru
Россия
I. B. Koptyaeva
Mechnikov Research Institute of Vaccines and Sera
Email: noemail@neicon.ru
Россия
K. V. Lisovskaya
Mechnikov Research Institute of Vaccines and Sera
Email: noemail@neicon.ru
Россия
References
- Гендон Ю.З., Маркушин С.Г., Цфасман Т.М. и др. Новые холодоадаптированные штаммы-доноры аттенуации для живых вакцин против гриппа. Вопросы вирусологии. 2013, 1: 11-17.
- Гендон Ю.З., Маркушин С.Г., Акопова И.И. и др. Аттенуированный холодоадаптированный штамм вируса гриппа А/Краснодар/ 101/35/59 (Н2№) для получения штаммов живой интраназальной гриппозной вакцины. Патент РФ на изобретение № 2354695.
- Гланц С. Медико-биологическая статистика. М., Практика, 1999.
- Свитич О.А., Ковальчук Л.В., Ганковская Л.В. и др. Аналитический подход в изучении противовирусного и иммуномодулирующего действия препаратов на модели герпесвирусной инфекции in vitro. Российский иммунологический журнал. 2013, 4: 377384.
- Терехов А.В., Цфасман Т.М., Маркушин С.Г. и др. Генетические основы аттенуации холодоадаптированного штамма А(Н2№)/Краснодар/101/35/59-донора для живых гриппозных вакцин. Эпидемиология и вакцинопрофилактика. 2013а, 3 (70): 70-77.
- Терехов А.В., Цфасман Т.М., Маркушин С.Г. и др. Изучение att- фенотипа реассортантов между вирулентным штаммом вируса гриппа А(Н1N1)/WSN/33 и вакцинным холодоадаптированным штаммом вируса гриппа А(Н2№)/Краснодар/101/35/59. Эпидемиология и вакцинопрофилактика. 2013b, 5 (72): 41-47.
- Gack M.U., Albrecht R.A., Urano T. et al. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-1. Cell Host Microbe.2009, 5: 439-449.
- Hoffmann E., Krauss S., Perez D. et al. Eight-plasmid system for rapid generation of influenza virus vaccines. Vaccine. 2002, 20: 3165-3170.
- Mibayashi M., Martinez-Sobrido L., Loo Y.M. et al. Inhibition of retinoic acid-inducible gene I-mediated induction ofbeta interferon by the NS1 protein of influenza A virus. J.Virol. 2007, 81: 514-524.
- Noah D.L., Twu K.Y., Krug R.M. Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3’ end processing of cellular pre-mRNAS. Virology. 2003, 307: 386395.
- Pichlmair A., Schulz O., Tan C.P. et al. Rig-1-mediated antiviral responses to single-stranded RNA bearing 5’ - phosphates. Science. 2006, 314: 997-1001.
- Rei-Lin Kuo, Krug R. M. Influenza A virus polymerase is an integral component of the CPSF30-NS1A protein complex in infected cells. J. Virol. 2009, 83: 1611-1616.
- Tsfasman T.M., Markushin S.G., Akopova I.I. et al. Molecular mechanisms of reversion to the ts+ phenotype of influenza a cold-adapted (ca)virus strain. J. Gen. Virol. 2007,88: 27242729.
- Wang W, Krug R.M. The RNA-binding and effector domains of the viral NS1 protein are conserved to different extents among influenza A and B viruses. Virology.1996, 223: 41-50.
Supplementary files
