Variable loci of HA, NA and NP genes as effective RNA targets for genotyping subtypes H1N1 and H7N9
Abstract
Aim. Influenza viruses are a serious pathogen of humans, animals and birds that regularly cause epidemics. Antigenic variability and reassortment of influenza A virus genes represent 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 the H1 and H7 influenza virus will allow the establishment of RNA targets for genotyping. Methods. An analysis of substitution of nucleotides in the encoding regions of influenza A subtype genes of various antigenic subtypes obtained from the GenBank database using the MEGA 6.0 program determined the fate of synonymous and non-synonymous substitutions in each position of multiple alignments of the coding regions of the nucleotide sequences using the BLAST algorithm. The analysis of variable locus of proteins was determined by the DISORDER algorithm. Results. Different types of mutations are found in variable locus of the studied genes. The most variable genes are HA and NA, the least NP. In sequences of the NP gene synonymous nucleotide substitutions prevail. The genome of NA is mainly deletions and insertions. Conclusions. The variability of the nucleotide sequences of the HA, NA and NP genes in the subtypes A H1 and H7 was detected. It has been established that the use of variable locus of these genes allows for the identification of influenza A strains and identifies a separate serotype.Keywords: neurominidase, variability, genetic markers, target RNA, genotyping.
References
Webby R., Hoffmann E., Webster R. Molecular constraints to interspecies transmission of viral pathogens. Nat. Med. 2004. Vol. 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 real-time RT-PCR assay. BMC. Infect. Dis. 2014. Vol. 14. P. 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. Vol. 360. P. 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., Os-terhaus A.D., Rottier P.J. Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pande-mic swine-origin 2009 A(H1N1) influenza virus infection in ferrets. J. Virol. 2010. Vol. 84. P. 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. Vol. 47. P. 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. Vol. 368. P. 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. Vol. 368. P. 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. Vol. 203. P. 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. Vol. 9. e88728. doi: 10.1371/journal.pone.0088728.
Li H., He Z. Magnetic bead-based DNA hybridization assay with chemiluminescence and chemiluminescent imaging detec-tion. Analyst. 2009. Vol. 134. P. 800–804. doi: 10.1039/b819990f.
Ma E.J., Hill N.J., Zabilansky J., Yuan K., Runstadler J.A. Reticulate evolution is favored in influenza niche switching. Proc. Natl. Acad. Sci. USA. 2016. Vol. 113 (19). P. 5335–5344.
McDonald S.M., Nelson M.I., Turner P.E., Patton J.T. Reassortment in segmented RNA viruses: mechanisms and outcomes. Nat. Rev. Microbiol. 2016. Vol. 14 (7). P. 448–450.