Comparative Analysis of Avian Influenza Virus Diversity in Poultry and Humans during a Highly Pathogenic Avian Influenza A (H7N7) Virus Outbreak
Comparative Analysis of Avian Influenza Virus Diversity in Poultry and Humans during a Highly Pathogenic Avian Influenza A (H7N7) Virus Outbreak
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DOI：
10.1128/jvi.05369-11
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发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Koopmans, Marion
中科院分区：
文献类型：
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作者：
Jonges, Marcel;Bataille, Arnaud;Koopmans, Marion
尽管越来越多的数据表明人类适应与非人流感病毒的特定分子变化有关，但在家禽中沿着禽-人传播的大规模高致病性禽流感病毒（HPAI）爆发期间，这些病毒的分子变化从未被记录。通过对2003年荷兰大规模HPAI A（H7 N7）爆发期间获得的兽医和人类样本进行全面的病毒学分析，我们绘制了人类适应标志物的获取图，以确定与家禽HPAI爆发相关的公共卫生风险。从45例人类病例中获得的A（H7 N7）病毒的全长血凝素（HA）、神经氨酸酶（NA）和PB 2测序显示HA（n = 20）、NA（n = 23）和PB 2（n = 23）中不同密码子的氨基酸变异。基于232个农场序列对人类病毒感染的禽类来源的鉴定表明，对于每个基因，约50%的变异已经存在于家禽中。在A（H7 N7）病毒感染的家禽中，已知毒力和人类适应标记的多基因积累和农场到农场传播发生在农场到人传播之前。这些包括HA A143 T突变体的独立出现，四种NA突变的积累，以及PB 2中携带哺乳动物宿主决定簇D 701 N和S714 I的病毒变体在农场间的传播。这意味着具有大流行潜力的高致病性禽流感病毒可以直接从家禽中出现。由于家禽中禽流感病毒爆发的公共卫生风险可能迅速变化，我们建议在家禽爆发期间对家禽和人类之间的人类适应标志物进行病毒学监测。
Although increasing data have become available that link human adaptation with specific molecular changes in nonhuman influenza viruses, the molecular changes of these viruses during a large highly pathogenic avian influenza virus (HPAI) outbreak in poultry along with avian-to-human transmission have never been documented. By comprehensive virologic analysis of combined veterinary and human samples obtained during a large HPAI A (H7N7) outbreak in the Netherlands in 2003, we mapped the acquisition of human adaptation markers to identify the public health risk associated with an HPAI outbreak in poultry. Full-length hemagglutinin (HA), neuraminidase (NA), and PB2 sequencing of A (H7N7) viruses obtained from 45 human cases showed amino acid variations at different codons in HA (n = 20), NA (n = 23), and PB2 (n = 23). Identification of the avian sources of human virus infections based on 232 farm sequences demonstrated that for each gene about 50% of the variation was already present in poultry. Polygenic accumulation and farm-to-farm spread of known virulence and human adaptation markers in A (H7N7) virus-infected poultry occurred prior to farm-to-human transmission. These include the independent emergence of HA A143T mutants, accumulation of four NA mutations, and farm-to-farm spread of virus variants harboring mammalian host determinants D701N and S714I in PB2. This implies that HPAI viruses with pandemic potential can emerge directly from poultry. Since the public health risk of an avian influenza virus outbreak in poultry can rapidly change, we recommend virologic monitoring for human adaptation markers among poultry as well as among humans during the course of an outbreak in poultry.