A novel Enterovirus 96 circulating in China causes hand, foot, and mouth disease Yi Xu 1 • Yisuo Sun 2 • Jinmin Ma 2 • Shuru Zhou 1,3 • Wei Fang 2 • Jiawei Ye 1 • Limei Tan 1 • Jingkai Ji 2 • Dan Luo 1 • Liqiang Li 2 • Jiandong Li 2 • Chunxiao Fang 1 • Na Pei 2 • Shuo Shi 2 • Xin Liu 2 • Hui Jiang 2 • Sitang Gong 1 • Xun Xu 2 Received: 4 May 2016 / Accepted: 27 January 2017 Ó Springer Science+Business Media New York 2017 Abstract Enterovirus 96 (EV-96) is a recently described member of the species Enterovirus C and is associated with paralysis and myelitis. In this study, using metagenomic sequencing, we identified a new enterovirus 96 strain (EV- 96-SZ/GD/CHN/2014) as the sole pathogen causing hand, foot, and mouth disease (HFMD). A genomic comparison showed that EV-96-SZ/GD/CHN/2014 is most similar to the EV-96-05517 strain (85% identity), which has also been detected in Guangdong Province. This is the first time that metagenomic sequencing has been used to identify an EV-96 strain shown to be associated with HFMD. Keywords Enterovirus 96  Metagenomics  HFMD  Genome sequence  Evolution Introduction The human enteroviruses (HEVs) are members of the genus Enterovirus in the family Picornaviridae and the order Picornavirales. Enteroviruses are common causes of a wide range of human diseases, including acute aseptic meningitis, acute myocarditis, acute flaccid paralysis, pancreatitis, and hand, foot, and mouth disease (HFMD) [1–3]. The enteroviral genome is a single-stranded RNA of approximately 7.5 kb, containing a long open reading frame flanked by 5 0 and 3 0 untranslated regions (UTRs) [4]. HEVs are classified into four species, Enterovirus A–D, and enterovirus 96 (EV-96) that is a member of the HEV-C class [5]. The prototype virus was isolated in 2000 from a stool specimen of a patient with acute flaccid paralysis (AFP) in Bangladesh. Since then, EV-96 strains have been reported in Cambodia, Slovakia, Finland, Bolivia, the Philippines, and China [6–13]. In this study, we report an EV-96 strain from a patient with suspected HFMD in Guangzhou, Guangdong Province, China, which was sequenced in 2014. Materials and methods Sample collection A fecal sample was collected from a patient diagnosed with HFMD who attended the Guangzhou Women and Chil- dren’s Medical Center in July 2014. This study was approved by the Ethical Committee of the Institutional Review Board (BGI-IRB) in Shenzhen (BGI-IRB 14038), and informed consent was obtained from the parents of the child before the study. The fecal sample was stored at -80 °C immediately after collection. Edited by William Dundon. Yi Xu, Yisuo Sun, Jinmin Ma have contributed equally to this work. Electronic supplementary material The online version of this article (doi:10.1007/s11262-017-1431-5) contains supplementary material, which is available to authorized users. & Sitang Gong sitangg@126.com & Xun Xu xuxun@genomics.cn 1 Department of Infectious Disease, Guangzhou Women and Children’s Medical Center, Jinsui Road No. 9, Guangzhou 510120, China 2 BGI-Shenzhen, Shenzhen 518083, China 3 Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou 510120, China 123 Virus Genes DOI 10.1007/s11262-017-1431-5