Identification of a new recombinant strain of echovirus 33 from children with hand, foot, and mouth disease complicated

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Identification of a new recombinant strain of echovirus 33 from children with hand, foot, and mouth disease complicated by meningitis in Yunnan, China Jie Zhang1,2†, Hongbo Liu1,2†, Yilin Zhao1,2, Haihao Zhang1,2, Hao Sun1,2, Xiaoqin Huang1,2, Zhaoqing Yang1,2, Jiansheng Liu1,2* and Shaohui Ma1,2*

Abstract Background: Hand, foot, and mouth disease (HFMD) is a common childhood disease, which is usually caused by enterovirus A (EV-A) serotypes. Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are the main etiologic agents. Multiple serotypes of enterovirus B serotypes (EV-B) have been detected in outbreaks or sporadic cases of HFMD. Results: During HFMD surveillance in Yunnan, China in 2013, two echovirus 33 (E-33) isolates were recovered in cell culture and typed by molecular methods from the cerebrospinal fluid (CSF) and feces of two sporadic cases of HFMD complicated by meningitis. Sequence analysis indicated that the study isolates, YNK35 and YNA12, formed an independent branch, and belonged to E-33 genotype H. Recombination analysis indicated multiple recombination events in the genomic sequence of isolate YNK35. The recombination mainly occurred in the nonstructural coding region of P2 and P3, and involved intra-species recombination of species B. Conclusion: In this study, the complete sequences of two E-33 isolates were determined. This is the first report of severe HFMD associated with E-33 in Yunnan China, and it enriches the number of full-length genome sequences of E-33 in the GenBank database. Keywords: HFMD, E-33, Recombination

Background Enteroviruses (EVs) are small, positive, single-stranded, non-enveloped RNA viruses belonging to the family Picornaviridae, which are further classified into fifteen species: enterovirus (EV)-A, EV-B, EV-C, EV-D, EV-E, EV-F, EV-G, EV-H, EV-I, EV-J, EV-K, and EV-L and rhinovirus (RV)-A, RV-B, and RV-C [1]. EVs cause a wide range of human diseases worldwide, including cutaneous, visceral, and neurological disorders. Among these diseases, hand, foot, and mouth disease (HFMD) is a common childhood disorder which typically presents as a brief, febrile illness * Correspondence: [email protected]; [email protected]; [email protected] † Jie Zhang and Hongbo Liu contributed equally to this work. 1 Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, People’s Republic of China Full list of author information is available at the end of the article

characterized by the association of oral ulcerations (enanthema) and vesicular rash (exanthema) on the palms, soles, and buttocks [2]. EV-A71 and CV-A16 are the major etiological agents of HFMD [3, 4]. Serotypes of EV-B (Es) have been mainly related to herpangina and seasonal outbreaks of mild viral meningitis, but have recently been associated with epidemics of HFMD. Echovirus (E) belongs to species EV-B. And multiple E serotypes are detected in sporadic cases or outbreaks of HFMD, and frequently co-circulated with EV-A71 and CV-A16