Molecular Epidemiology of Echovirus 18 Circulating in Mainland China from 2015 to 2016
Echovirus 18 (E18), a serotype of Enterovirus B (EV-B) species, is an important pathogen in aseptic meningitis. E18 had rarely been detected in mainland China, but became the predominant pathogen associated with viral encephalitis (VE) and meningitis in Hebei province for the first time in 2015. To investigate the molecular epidemiology and genetic characteristics of E18 in mainland China, sixteen E18 strains from patient throat swabs with hand, foot, and mouth disease (HFMD) in six provinces in China collected between 2015 and 2016, and four E18 strains isolated from 18 patient cerebrospinal fluid specimens with VE in Hebei Province in 2015 were obtained and sequenced. Combined with the sequences from the GenBank database, we performed an extensive genetic analysis. Phylogenetic analysis of VP1 gene sequences revealed that all E18 strains from mainland China after 2015 belonged to subgenotype C2. There were no obvious specific differences in phylogenetic and variation analyses of E18 genome sequences between HFMD and VE/meningitis strains. Potential multiple recombination may have occurred in the 5′-untranslated region and in the P2 and P3 nonstructural protein-encoding regions of E18 strains from China. The current E18 strains were potential multiple-recombinant viruses. Overall, these findings supported that E18 caused HFMD, VE, and meningitis, although there were no significant associations between clinical features and viral genomic characteristics.
KeywordsGenetic characteristics Echovirus 18 (E18) Genome Enterovirus Recombination
This work was supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China (Grant Nos. 2017ZX10104001-005-010 and 2017ZX10103004-004); Beijing Natural Science Foundation (Grant No. 7184208); Capital Clinical Feature Project of Beijing Technology Program (Grant No. Z151100004015046); Basic and Clinical Research Cooperation Project of Capital Medical University (Grant No. 17JL11); and Research Training Fund of Capital Medical University (Grant No. PYZ2017012). The sponsors had no role in the study design, data analysis, manuscript preparation, or publishing decision.
XC, ZX, and WX conceived and designed the experiments; XC, TJ, and JG performed the experiments; XC and WW analyzed the data; XC and ZX contributed to the writing of the manuscript. All authors reviewed and approved the final manuscript for submission.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Animal and Human Rights Statement
The study was approved by the Medical Ethics Committee of Beijing Children’s Hospital, Capital Medical University (Permit No. 2015-8). Informed consents were obtained from legal guardians of all patients prior to the collection of CSF and throat swab samples.
- Chen P, Song Z, Qi Y, Feng X, Xu N, Sun Y, Wu X, Yao X, Mao Q, Li X, Dong W, Wan X, Huang N, Shen X, Liang Z, Li W (2012) Molecular determinants of enterovirus 71 viral entry: cleft around GLN-172 on VP1 protein interacts with variable region on scavenge receptor B 2. J Biol Chem 287:6406–6420CrossRefGoogle Scholar
- Chen X, Li J, Guo J, Xu W, Sun S, Xie Z (2017) An outbreak of echovirus 18 encephalitis/meningitis in children in Hebei Province, China, 2015. Emerg Microbes Infect 6:e54Google Scholar
- Krumbholz A, Egerer R, Braun H, Schmidtke M, Rimek D, Kroh C, Hennig B, Groth M, Sauerbrei A, Zell R (2016) Analysis of an echovirus 18 outbreak in Thuringia, Germany: insights into the molecular epidemiology and evolution of several enterovirus species B members. Med Microbiol Immunol 205:471–483.CrossRefGoogle Scholar
- Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, Ray SC (1999) Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 73:152–160Google Scholar
- Miyamura K, Yamashita K, Yamadera S, Kato N, Akatsuka M, Yamazaki S (1990) An epidemic of echovirus 18 in 1988 in Japan–high association with clinical manifestation of exanthem. A report of the National Epidemiological Surveillance of Infectious Agents in Japan. Jpn J Med Sci Biol 43:51–58CrossRefGoogle Scholar
- Reimann BY, Zell R, Kandolf R (1991) Mapping of a neutralizing antigenic site of Coxsackievirus B4 by construction of an antigen chimera. J Virol 65:3475–3480Google Scholar
- Turabelidze G, Lin M, Butler C, Fick F, Russo T (2009) Outbreak of echovirus 18 meningitis in a rural Missouri community. Mo Med 106:420–424Google Scholar
- Zhang Y, Wang J, Guo W, Wang H, Zhu S, Wang D, Bai R, Li X, Yan D, Wang H, Zhang Y, Zhu Z, Tan X, An H, Xu A, Xu W (2011) Emergence and transmission pathways of rapidly evolving evolutionary branch C4a strains of human enterovirus 71 in the Central Plain of China. PLoS ONE 6:e27895CrossRefGoogle Scholar