Published August 9, 2019 | Version v1
Journal article Open

Варіабельні локуси генів HA, NA та NP як ефективні РНК- мішені для генотипування субтипів H1N1 та H7N9

  • 1. NSC Institute experimental and clinical veterinary medicine

Description

VARIABLE LOCUS OF HA, NA AND NP GENES AS EFFECTIVE RNA TARGETS FOR GENOTYPING SUBTYPES A(H1N1) AND A(H7N9) 
 
Aim.Influenza viruses are a serious pathogen of humans, animals and birds that regularly cause epidemics, as well as high-mortality pandemics. The H7N9 virus, apathetic to birds, is highly virulent for humans. Antigenic variability and reassortment of influenza A virus genes are a high level of neonatal data, which does not allow to assess the evolutionary stability of proteins. Determination of variable HA, NA and NP gene loci of two different antigenic subtypes of influenza A H1N1 and H7N9 viruses will allow the establishment of RNA targets for genotyping. Methods. An analysis of 8,000 avian influenza A strains of various antigenic subtypes isolated from different hosts from the NCBI GenBank virus database using the MEGA 6.0 program determined the fate of synonymous and non-synonymous substitutions at each position of multiple alignments of the coding regions of the nucleotide sequences. The BLAST algorithm was used. The phylogenetic branches were obtained using the program using the UPGMA algorithm. Analysis of variable protein locus was determined by the DISORDER algorithm, which predicts internal disordered protein regions. Results. Different types of mutations are found in variable locus of the studied genes. The most variable genome is HA, least NP. In sequences of the NP gene synonymous nucleotide substitutions prevail. In the genome, NA is predominantly deletion, less insertion, and single-nucleotide substitution.  Conclusions. The variability of nucleotide sequences of HA, NA and NP genes in the subtypes of avian influenza AH1N1 and H7N9 was detected. It has been established that the use of variable locus of these genes allows for the intrinsic differentiation of strains of avian influenza A pathogen and to determine the affiliation of strains to a specific serotype.  Keywords: neurominidase, hemagglutinin, nucleoprotein, influenza virus, variability, genetic markers, target RNA, variable locus, genotyping

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References

  • Webby R., Hoffmann E., Webster R. 2004. Molecular constraints to interspecies transmission of viral pathogens. Nat. Med. 10: S77–S81
  • Cui D., Lau S., Xie G., Guo X., Zheng S., Huang X., Yang S., Yang X., Huo Z., et al. Detection of a novel avian influenza A (H7N9) virus in humans by multiplex one-step realtime RT-PCR assay. BMC. Infect. Dis. 2014;14:541. doi: 10.1186/1471-2334-14-541
  • Dawood F.S., Jain S., Finelli L., Shaw M.W., Lindstrom S., Garten R.J., Gubareva L.V., Xu X., Bridges C.B., Uyeki TM. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N. Engl. J. Med. 2009;360:2605–2615. doi: 10.1056/NEJMoa0903810
  • Bosch B.J., Bodewes R., de Vries R.P., Kreijtz J.H., Bartelink W., van Amerongen G, Rimmelzwaan G.F., de Haan C.A., Osterhaus A.D., Rottier P.J. (2010) Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets. J. Virol. 84:10366–10374
  • Gall A., Hoffmann B., Harder T., Grund C., Ehricht R., Beer M. Rapid and highly sensitive neuraminidase subtyping of avian influenza viruses by use of a diagnostic DNA microarray. J. Clin.Microbiol. 2009;47:2985–2988. doi: 10.1128/JCM.00850-09
  • Gao H.N., Lu H.Z., Cao B., Du B., Shang H., Gan J.H., Lu S.H., Yang Y.D., Fang Q., Shen Y.Z., et al. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N. Engl. J. Med. 2013;368:2277–2285. doi: 10.1056/NEJMoa1305584
  • Gao R., Cao B., Hu Y., Feng Z., Wang D., Hu W., Chen J., Jie Z., Qiu H., Xu K., et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N. Engl. J. Med. 2013;368:1888–1897. doi: 10.1056/NEJMoa1304459
  • Ghedin E., Laplante J., DePasse J., Wentworth D.E., Santos R.P., Lepow M.L., Porter J., Stellrecht K., Lin X., Operario D., et al. Deep sequencing reveals mixed infection with 2009 pandemic influenza A (H1N1) virus strains and the emergence of oseltamivir resistance. J. Infect. Dis. 2011;203:168–174. doi: 10.1093/infdis/jiq040
  • Lu S., Li T., Xi X., Chen Q., Liu X., Zhang B., Ou J., Liu J., Wang Q., Zhu B., et al. Prognosis of 18 H7N9 avian influenza patients in Shanghai. PLoS ONE. 2014;9:e88728. doi: 10.1371/journal.pone.0088728
  • Li H., He Z. Magnetic bead-based DNA hybridization assay with chemiluminescence and chemiluminescent imaging detection. Analyst. 2009;134:800–804. doi: 10.1039/b819990f.
  • Ma, E. J. Reticulate evolution is favored in influenza niche switching/E. J. Ma, N. J. Hill, J. Zabilansky, K. Yuan, J. A. Runstadler//Proc. Natl. Acad. Sci. USA. – 2016. – V. 113 (19). – P. 5335–5344
  • McDonald, S. M. Reassortment in segmented RNA viruses: mechanisms and outcomes/S. M. McDonald, M. I. Nelson, P. E. Turner, J. T. Patton//Nat. Rev. Microbiol. – 2016. – V. 14 (7). – P. 448–508