DEVELOPMENT OF A PCR PROTOCOL FOR THE DETECTION OF HUMAN ENTEROVIRUSES BASED ON THE ANALYSIS OF THE 5'-NTR REGION AND IT’S USE IN MOLECULAR EPIDEMIOLOGY

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Authors

D.K. Kamalova

National Center for Biotechnology, 13/5, Korgalzhyn road, Astana, 010000, Kazakhstan

M.A. Kuybagarov

National Center for Biotechnology, 13/5, Korgalzhyn road, Astana, 010000, Kazakhstan

A.B. Abeev

National Center of Expertise, Zheltoksan str., 46,  Astana, 010000, Kazakhstan

V.B. Shvedyuk

National Center for Biotechnology, 13/5, Korgalzhyn road, Astana, 010000, Kazakhstan

K.O. Balykbaev

National Center of Expertise, Zheltoksan str., 46,  Astana, 010000, Kazakhstan

L.S. Kiyanbekova

National Center of Expertise, Zheltoksan str., 46,  Astana, 010000, Kazakhstan

Z.T. Aushakhmetova

National Center of Expertise, Zheltoksan str., 46,  Astana, 010000, Kazakhstan

A.B. Shevtsov

National Center for Biotechnology, 13/5, Korgalzhyn road, Astana, 010000, Kazakhstan

Abstract

Enterovirus infections are widespread throughout the world. The clinical manifestation of enterovirus infection can lead to serious and fatal complications. Express PCR diagnosis and genotyping allows controlling the epidemiological situation and predicting the severity of the infection. In Kazakhstan, there are no locally produced PCR test kits. In addition there is no regular monitoring of circulating genotypes of enteroviruses. This study was aimed to develop a PCR protocol for the enterovirus detection based on the amplification of the 5' untranslated region (5' NTR) and genotyping by sequencing of enteroviruses circulating in Kazakhstan in 2016 - 2017. In this study 74 cDNA samples were used. The results obtained with developed protocol were well correlated (97.3%) with the results of the commercial PCR testing kit. The advantage of the developed protocol is genotyping of enteroviruses by sequencing of the amplified DNA fragment. Fifty nine samples were genotyped, of which 54.7% belong to enterovirus B, 35.9% are classified as enterovirus A and 1.56% are classified as enterovirus C. Ninety-three percent of meningitis-associated genotypes were identified as enterovirus B, and clustered with E-9, E-18, CV-B5 and E-30. Samples of DNA that isolated from patients with enterovirus infection were clustered with the CV-A6 genotype.

Keywords

enterovirus, PCR, genotyping, 5 'NTR region, serous meningitis, intestinal infection

Article Details

References

Xiang Z., Tsatsral S., Liu C. et al. Respiratory infection with enterovirus genotype C117, China and Mongolia. Emerg. Infect. Dis., 2014, vol. 20, pp. 1075-1077.

Xing W., Liao Q., Viboud C. et al. Hand, foot, and mouth disease in China, 2008-12: an epidemiological study. Lancet. Infect., Dis., 2014, vol. 14, pp. 308-318.

Gorgievski-Hrisoho M., Schumacher J.D., Vilimonovic N. et al. Detection by PCR of enteroviruses in cerebrospinal fluid during a summer outbreak of aseptic meningitis in Switzerland. J.Clin.Microbiol., 1998, vol. 36, pp. 2408-2412.

Romero J.R. Reverse-transcription polymerase chain reaction detection of the enteroviruses. Arch. Pathol. Lab. Med., 1999, vol. 123, pp. 1161-1169.

Thoelen I., Lemey P., I. Van der Donck et al. Molecular typing and epidemiology of enteroviruses identified from an outbreak of aseptic meningitis in Belgium during the summer. J. Med. Virol., 2000, vol. 70, pp. 420-429.

Tsao K.C., Huang C.G., Huang Y.L. et al. Epidemiologic features and virus isolation of enteroviruses in Northern Taiwan during 2000-2008. J. Virol. Methods., 2010, vol. 165, pp. 330-332.

Singh S., Chow V.T., Phoon M.C. et al. Direct detection ofenterovirus 71 (EV71) in clinical specimens from a hand, foot, and mouth diseaseoutbreak in Singapore by reverse transcription-PCR with universal enterovirusand EV71-specific primers. J. Clin. Microbiol., 2002, vol. 40, pp. 2823-2827.

Oberste M.S., Maher K., Kilpatrick D.R., Pallansch M.A. Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. J. Jurnal. Virology, 1999, vol. 73, pp. 1941-1948.

WHO/CDC Enterovirus surveillance guidelines. Denmark, World Health Organization, 2015, vol. 46.

Ibrahim W., Ouerdani I., Pillet S. et al. Direct typing of human enteroviruses from wastewater samples. J. Virol. Methods., 2014, vol. 207, pp. 215-219.

Iturriza-Gomara M., Megson B., Gray J. Molecular detection and characterization of human enteroviruses directly from clinical samples using RT-PCR and DNA sequencing. J. Med. Virol., 2006, vol. 78, pp. 243-253.

Ge S., Yan Q., He S. et al. Specific primer amplification of the VP1 region directed by 5' UTR sequence analysis: enterovirus testing and identification in clinical samples from hand-foot-and-mouth disease patients. J. Virol. Methods., 2013, vol. 193, pp. 463-469.

Hu L., Zhang Y., Hong M. et al. Phylogenetic evidence for multiple intertypic recombinations in enterovirus B81 strains isolated in Tibet, China. Scientific reports., 2014, vol. 12.

Tsai C.S., Yang Y.H. et al. Association of Tic Disorders and Enterovirus Infection: A Nationwide Population-Based Study. Medicine., 2016, vol. 95.

Thoelen I., Lemey P., I. Van der Donck et al. Molecular typing and epidemiology of enteroviruses identified from an outbreak of aseptic meningitis in Belgium during the summer. J. Med. Virol., 2000, vol. 70, pp. 420-429.

Xiang Z., Gonzalez R., Xie Z. et al. Human rhinovirus C infections mirror those of human rhinovirus A in children with community-acquired pneumonia. J. Clin. Virol., 2010, vol. 49, pp. 94-99.

Tapparel C., Junier T., Gerlach D. et al. New respiratory enterovirus and recombinant rhinoviruses among circulating picornaviruses. Emerg Infect Dis., 2009, vol. 15, pp. 719-726.

Simmonds P., Welch J. Frequency and dynamics of recombination within different species of human enteroviruses. J. Virol., 2006, vol. 80, pp. 483-493.

Dumaidi K., Al-Jawabreh A. Molecular detection and genotyping of enteroviruses from CSF samples of patients with suspected sepsis-like illness and/or aseptic meningitis from 2012 to 2015 in West Bank, Palestine. PLoS One., 2017, vol. 22, pp. 12.

Li J., Sun Y., Du Y., Yan Y. et al. Characterization of Coxsackievirus A6- and Enterovirus 71-Associated Hand Foot and Mouth Disease in Beijing, China, from 2013 to 2015. Front. Microbiol., 2016, vol. 30, pp. 391.

Flett K., Youngster I., Huang J. et al. Hand, foot, and mouth disease caused by coxsackievirus a6. Emerg. Infect. Dis., 2012, vol. 18, pp. 1702.

Chen P., Tao Z., Song Y. et al. A coxsackievirus B5-associated aseptic meningitis outbreak in Shandong Province, China in 2009. J. Med. Virol., 2013, vol. 483, pp. 85.