Marburgvirus Genomics and association with a large hemorrhagic fever outbreak in Angola
Marburgvirus Genomics and association with a large hemorrhagic fever outbreak in Angola
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DOI：
10.1128/jvi.00069-06
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发表时间：
2006-07-01
影响因子：
5.4
通讯作者：
Nichol, Stuart T.
中科院分区：
文献类型：
--
作者：
Towner, Jonathan S.;Khristova, Marina L.;Nichol, Stuart T.
2005年3月，疾病控制和预防中心（CDC）调查了西非安哥拉北部威热省的一次大规模出血热暴发。总共有15个初始样本被送往乔治亚州亚特兰大的疾病预防控制中心。用于检测与西非已知存在的病毒性肝炎相关的病毒，包括埃博拉病毒。马尔堡病毒也被包括在内，尽管所有早期疫情的源头都与东非直接相关。令人惊讶的是，马堡病毒（15个标本中的12个）被确认为暴发的原因。疫情可能始于2004年10月并于2005年7月结束，其中包括252例和227例（90%）死亡（安哥拉共和国卫生部2005年报告），使其成为有记录以来最大的马尔堡HF疫情。疫情期间使用和调整的实时定量逆转录- pcr测定被证明具有高度敏感性和足够强的野外应用能力。部分马尔堡病毒RNA序列分析显示，在以前鉴定的东非毒株中，核苷酸差异高达21%，其中最明显的是来自肯尼亚的Ravn（1987年）。安哥拉毒株与东非马尔堡病毒主要群体的差异（约为7%）比人们可能预期的要小，因为地理上存在很大的差异。为了更精确地分析疫情之间以及安哥拉疫情本身内部病毒之间的病毒遗传差异，共确定了16个完整的病毒基因组，包括病毒分离株Ravn（肯尼亚，1987年）、05DRC、07DRC和09DRC（刚果民主共和国，1998年）以及安哥拉参考病毒分离株Ang1379v的基因组。此外，从10个临床标本中提取的rna中获得了完整的基因组序列，反映了安哥拉疫情的不同阶段和地点。虽然马尔堡病毒表现出很高的总体遗传多样性（高达22%），但在西非安哥拉病毒和大多数东非病毒之间仅发现6.8%的核苷酸差异，这表明这些地区的病毒库物种并没有本质上的差异。在安哥拉临床标本中发现的核苷酸差异非常少（0 - 0.07%），这与暴发情景一致，即从宿主物种将病毒单次（或罕见地）引入人群，然后发生人与人之间的传播，几乎没有突变积累。这与1998年至2000年的马尔堡病毒暴发形成对比，当时发现了几种病毒遗传谱系（差异高达21%）和多种病毒传入人群的证据。
In March 2005, the Centers for Disease Control and Prevention (CDC) investigated a large hemorrhagic fever (HF) outbreak in Uige Province in northern Angola, West Africa. In total, 15 initial specimens were sent to CDC, Atlanta, Ga., for testing for viruses associated with viral HFs known to be present in West Africa, including ebolavirus. Marburgvirus was also included despite the fact that the origins of all earlier outbreaks were linked directly to East Africa. Surprisingly, marburgvirus was confirmed (12 of 15 specimens) as the cause of the outbreak. The outbreak likely began in October 2004 and ended in July 2005, and it included 252 cases and 227 (90%) fatalities (report from the Ministry of Health, Republic of Angola, 2005), making it the largest Marburg HF outbreak on record. A real-time quantitative reverse transcription-PCR assay utilized and adapted during the outbreak proved to be highly sensitive and sufficiently robust for field use. Partial marburgvirus RNA sequence analysis revealed up to 21% nucleotide divergence among the previously characterized East African strains, with the most distinct being Ravn from Kenya (1987). The Angolan strain was less different (similar to 7%) from the main group of East African marburgviruses than one might expect given the large geographic separation. To more precisely analyze the virus genetic differences between outbreaks and among viruses within the Angola outbreak itself, a total of 16 complete virus genomes were determined, including those of the virus isolates Ravn (Kenya, 1987) and 05DRC, 07DRC, and 09DRC (Democratic Republic of Congo, 1998) and the reference Angolan virus isolate (Ang1379v). In addition, complete genome sequences were obtained from RNAs extracted from 10 clinical specimens reflecting various stages of the disease and locations within the Angolan outbreak. While the marburgviruses exhibit high overall genetic diversity (up to 22%), only 6.8% nucleotide difference was found between the West African Angolan viruses and the majority of East African viruses, suggesting that the virus reservoir species in these regions are not substantially distinct. Remarkably few nucleotide differences were found among the Angolan clinical specimens (0 to 0.07%), consistent with an outbreak scenario in which a single (or rare) introduction of virus from the reservoir species into the human population was followed by person-to-person transmission with little accumulation of mutations. This is in contrast to the 1998 to 2000 marburgvirus outbreak, where evidence of several virus genetic lineages (with up to 21% divergence) and multiple virus introductions into the human population was found.