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首页> 美国卫生研究院文献>PLoS Neglected Tropical Diseases >Genetic landscape and macro-evolution of co-circulatingCoxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republicof Congo 2008-2013
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Genetic landscape and macro-evolution of co-circulatingCoxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republicof Congo 2008-2013

机译：遗传循环的宏观格局与宏观演化民主共和国的柯萨奇病毒A和疫苗衍生的脊髓灰质炎病毒刚果2008-2013年

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Enteroviruses (EVs) are among the most common viruses infecting humans worldwide but only a few Non-Polio Enterovirus (NPEV) isolates have been characterized in the Democratic Republic of Congo (DR Congo). Moreover, circulating vaccine-derived polioviruses (PVs) [cVDPVs] isolated during multiple outbreaks in DR Congo from 2004 to 2018 have been characterized so far only by the sequences of their VP1 capsid coding gene. This study was carried to i) investigate the circulation and genetic diversity of NPEV and polio vaccine isolates recovered from healthy children and Acute Flaccid Paralysis (AFP) patients, ii) evaluate the occurrence of genetic recombination among EVs belonging to the Enterovirus C species (including PVs) and iii) identify the virological factors favoring multiple emergences of cVDPVs in DR Congo. The biological material considered in this study included i) a collection of 91 Sabin-like PVs, 54 cVDPVs and 150 NPEVs isolated from AFP patients between 2008 and 2012 in DR Congo and iii) a collection of 330 stool specimens collected from healthy children in 2013 in the Kasai Oriental and Maniema provinces of DR Congo. Studied virus isolates were sequenced in four distinct sub-genomic regions 5’-UTR, VP1, 2CATPase and 3Dpol. Resultingsequences were compared through comparative phylogenetic analyses. Virusisolation showed that 19.1% (63/330) healthy children were infected by EVsincluding 17.9% (59/330) of NPEVs and 1.2% (4/330) of type 3 Sabin-like PVs.Only one EV-C type, EV-C99 was identified among the NPEV collection from AFPpatients whereas 27.5% of the 69 NPEV isolates typed in healthy childrenbelonged to the EV-C species: CV-A13 (13/69), A20 (5/69) and A17 (1/69).Interestingly, 50 of the 54 cVDPVs featured recombinant genomes containingexogenous sequences in at least one of the targeted non-structural regions oftheir genomes: 5’UTR, 2CATPase and 3Dpol. Some of thesenon-vaccine sequences of the recombinant cVDPVs were strikingly related tohomologous sequences from co-circulating CV-A17 and A20 in the2CATPase region as well as to those from co-circulating CV-A13,A17 and A20 in the 3Dpol region. This study provided the firstevidence uncovering CV-A20 strains as major recombination partners of PVs. Highquality AFP surveillance, sensitive environmental surveillance and efficientvaccination activities remain essential to ensure timely detection and efficientresponse to recombinant cVDPVs outbreaks in DR Congo. Such needs are valid forany epidemiological setting where high frequency and genetic diversity ofCoxsackieviruses A13, A17 and A20 provide a conducive viral ecosystem for theemergence of virulent recombinant cVDPVs.
机译：肠病毒（EVs）是全世界人类最常见的病毒之一，但在刚果民主共和国（DR Congo）中只有少数非脊髓灰质炎性肠病毒（NPEV）分离株具有特征。此外，到目前为止，仅在2004年至2018年期间刚果民主共和国多次暴发期间分离出的循环疫苗衍生脊髓灰质炎病毒（cVDPV）的特征仅在于其VP1衣壳编码基因的序列。这项研究的目的是：i）研究从健康儿童和急性弛缓性麻痹（AFP）患者中回收的NPEV和脊髓灰质炎疫苗分离株的流通和遗传多样性，ii）评价属于肠道病毒C物种（包括PVs和iii）确定了刚果民主共和国中有利于cVDPV多次出现的病毒学因素。在这项研究中考虑的生物材料包括：i）在刚果民主共和国2008年至2012年之间从AFP患者中分离出的91种类似Sabin的PV，54 cVDPV和150种NPEV，iii）2013年从健康儿童中采集的330个粪便标本在刚果民主共和国的开赛东方省和马涅马省。在四个不同的亚基因组区域5'-UTR，VP1、2C ATPase 和3D pol 中对研究的病毒分离株进行测序。结果通过比较系统发育分析比较了这些序列。病毒隔离显示19.1％（63/330）的健康儿童被电动汽车感染包括17.9％（59/330）的NPEV和1.2％（4/330）的3型Sabin型PV。在AFP的NPEV集合中仅发现一种EV-C类型EV-C99患者，而在健康儿童中键入的69种NPEV分离株中有27.5％属于EV-C物种：CV-A13（13/69），A20（5/69）和A17（1/69）。有趣的是，在54个cVDPV中有50个具有重组基因组至少一个目标非结构区中的外源序列它们的基因组：5’UTR，2C ATPase 和3D pol 。其中一些重组cVDPV的非疫苗序列与共同循环中CV-A17和A20的同源序列2C ATPase 区域以及来自共同循环的CV-A13的区域，3D pol 区域中的A17和A20。这项研究提供了第一个证据表明CV-A20菌株是PV的主要重组伴侣。高优质的AFP监视，灵敏的环境监视和高效疫苗接种活动对于确保及时发现和有效仍然至关重要刚果民主共和国对重组cVDPVs爆发的反应。这样的需求对于任何流行病学背景，其中高频率和遗传多样性柯萨奇病毒A13，A17和A20为病毒提供了有益的病毒生态系统毒性重组cVDPV的出现。

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