Major Infectious Disease Control Key Laboratory and Shenzhen Public Service Platform of Pathogenic Microorganisms Repository, Institute of Pathogen Biology, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.
District Key Laboratory for Infectious Disease Prevention and Control, Longhua District Center for Disease Control and Prevention, Shenzhen, 518109, China.
Arch Virol. 2020 Oct;165(10):2213-2227. doi: 10.1007/s00705-020-04734-z. Epub 2020 Jul 14.
In this study, we investigated the epidemiology and molecular characteristics of enteroviruses associated with severe hand, foot and mouth disease (HFMD) in Shenzhen, China, during 2014-2018. A total of 137 fecal specimens from patients with severe HFMD were collected. Enterovirus (EV) types were determined using real-time reverse transcription polymerase chain reaction (RT-PCR), RT nested PCR, and sequencing. Sequences were analyzed using bioinformatics programs. Of 137 specimens tested, 97 (70.8%), 12 (8.8%), and 10 (7.3%) were positive for EV-A71, coxsackievirus A6 (CVA6), and CVA16, respectively. Other pathogens detected included CVA2 (2.9%, 4/137), CVA10 (2.9%, 4/137), CVA5 (0.7%, 1/137), echovirus 6 (E6) (0.7%, 1/137) and E18 (0.7%, 1/137). The most frequent complication in patients with proven EV infections was myoclonic jerk, followed by aseptic encephalitis, tachypnea, and vomiting. The frequencies of vomiting and abnormal eye movements were higher in EV-A71-infected patients than that in CVA6-infected or CVA16-infected patients. Molecular phylogeny based on the complete VP1 gene revealed no association between the subgenotype of the virus and disease severity. Nevertheless, 12 significant mutations that were likely to be associated with virulence or the clinical phenotype were observed in the 5'UTR, 2A, 2C, 3A, 3D and 3'UTR of CVA6. Eight significant mutations were observed in the 5'UTR, 2B, 3A, 3D and 3'UTR of CVA16, and 10 significant mutations were observed in the 5'UTR, VP1, 3A and 3C of CVA10. In conclusion, EV-A71 is still the main pathogen causing severe HFMD, although other EV types can also cause severe complications. Potential virulence or phenotype-associated sites were identified in the genomes of CVA6, CVA16, and CVA10.
在这项研究中，我们调查了 2014 年至 2018 年期间在中国深圳与严重手足口病（HFMD）相关的肠病毒的流行病学和分子特征。共采集了 137 例严重 HFMD 患者的粪便标本。使用实时逆转录聚合酶链反应（RT-PCR）、RT 巢式 PCR 和测序来确定肠道病毒（EV）类型。使用生物信息学程序对序列进行分析。在 137 个检测样本中，EV-A71、柯萨奇病毒 A6（CVA6）和 CVA16 的阳性率分别为 70.8%（97/137）、8.8%（12/137）和 7.3%（10/137）。检测到的其他病原体包括 CVA2（2.9%，4/137）、CVA10（2.9%，4/137）、CVA5（0.7%，1/137）、肠道病毒 6（E6）（0.7%，1/137）和 E18（0.7%，1/137）。在证实有 EV 感染的患者中，最常见的并发症是肌阵挛性抽搐，其次是无菌性脑炎、呼吸急促和呕吐。与 CVA6 或 CVA16 感染患者相比，EV-A71 感染患者呕吐和眼球运动异常的频率更高。基于完整 VP1 基因的分子系统发育分析显示，病毒亚基因型与疾病严重程度之间没有关联。然而，在 CVA6 的 5'UTR、2A、2C、3A、3D 和 3'UTR 中观察到 12 个可能与毒力或临床表型相关的显著突变，在 CVA16 的 5'UTR、2B、3A、3D 和 3'UTR 中观察到 8 个显著突变，在 CVA10 的 5'UTR、VP1、3A 和 3C 中观察到 10 个显著突变。总之，EV-A71 仍然是引起严重 HFMD 的主要病原体，尽管其他肠道病毒类型也可能导致严重并发症。在 CVA6、CVA16 和 CVA10 的基因组中发现了与潜在毒力或表型相关的位点。
