Tissue Tropism of Swine Influenza Viruses and Reassortants in Ex Vivo Cultures of the Human Respiratory Tract and Conjunctiva
Tissue Tropism of Swine Influenza Viruses and Reassortants in Ex Vivo Cultures of the Human Respiratory Tract and Conjunctiva
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DOI：
10.1128/jvi.05662-11
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发表时间：
2011-11-01
影响因子：
5.4
通讯作者：
Chan, Michael C. W.
中科院分区：
文献类型：
--
作者：
Chan, Renee W. Y.;Kang, Sara S. R.;Chan, Michael C. W.
2009年大流行性H1N1(H1N1pdm)病毒是由不同谱系的猪流感病毒重新分类产生的。这是40多年来出现的第一次流感大流行，也是在认识到流感大流行是由动物的流感病毒引起后发生的第一次。为了了解大流行出现的生物学决定因素，比较不同谱系的猪流感病毒及其衍生的重组体与2009年大流行H1N1(H1N1pdm)和季节性H1N1病毒在人鼻咽、支气管、肺泡和结膜体外培养中的趋向性是相关的。我们假设，可以在人类之间有效传播的病毒在人类上呼吸道复制得很好。正如之前报道的，H1N1pdm和季节性H1N1病毒在鼻咽、支气管和肺泡上皮细胞中有效复制。相比之下，经典猪(CS)(H1N1)谱系的代表性病毒不能感染人的呼吸道上皮；欧亚类鸟猪(EA)(H1N1)病毒只感染肺泡上皮，北美三重组体(TRIG)病毒只感染呼吸道上皮，尽管效率较低。有趣的是，一种自然产生的三重配猪病毒A/Sw/HK/915/04(H1N2)具有EA猪源的基质基因片段(即与H1N1pdm不同的是缺少EA源的神经氨酸酶[NA]基因)，该病毒很容易在人的鼻咽和支气管上皮细胞中感染和复制，但在肺中不能。含有H1N1pdm的NA的重组sw915保留了其对支气管的趋向性，并获得了对肺泡上皮细胞的额外复制能力。与H1N1pdm不同的是，测试的猪病毒和季节性H1N1病毒都没有在人结膜上的嗜性。H1N1pdm和季节性H1N1病毒表面蛋白(血凝素和NA)互换产生的重组病毒表明，这两个基因片段共同是结膜嗜好的关键决定因素。总体而言，这些发现表明，人类呼吸道的体外培养为评估猪流感病毒对人类健康的风险提供了一个有用的生物学模型。
The 2009 pandemic influenza H1N1 (H1N1pdm) virus was generated by reassortment of swine influenza viruses of different lineages. This was the first influenza pandemic to emerge in over 4 decades and the first to occur after the realization that influenza pandemics arise from influenza viruses of animals. In order to understand the biological determinants of pandemic emergence, it is relevant to compare the tropism of different lineages of swine influenza viruses and reassortants derived from them with that of 2009 pandemic H1N1 (H1N1pdm) and seasonal influenza H1N1 viruses in ex vivo cultures of the human nasopharynx, bronchus, alveoli, and conjunctiva. We hypothesized that virus which can transmit efficiently between humans replicated well in the human upper airways. As previously reported, H1N1pdm and seasonal H1N1 viruses replicated efficiently in the nasopharyngeal, bronchial, and alveolar epithelium. In contrast, representative viruses from the classical swine (CS) (H1N1) lineage could not infect human respiratory epithelium; Eurasian avian-like swine (EA) (H1N1) viruses only infected alveolar epithelium and North American triple-reassortant (TRIG) viruses only infected the bronchial epithelium albeit inefficiently. Interestingly, a naturally occurring triple-reassortant swine virus, A/SW/HK/915/04 (H1N2), with a matrix gene segment of EA swine derivation (i.e., differing from H1N1pdm only in lacking a neuraminidase [NA] gene of EA derivation) readily infected and replicated in human nasopharyngeal and bronchial epithelia but not in the lung. A recombinant sw915 with the NA from H1N1pdm retained its tropism for the bronchus and acquired additional replication competence for alveolar epithelium. In contrast to H1N1pdm, none of the swine viruses tested nor seasonal H1N1 had tropism in human conjunctiva. Recombinant viruses generated by swapping the surface proteins (hemagglutinin and NA) of H1N1pdm and seasonal H1N1 virus demonstrated that these two gene segments together are key determinants of conjunctival tropism. Overall, these findings suggest that ex vivo cultures of the human respiratory tract provide a useful biological model for assessing the human health risk of swine influenza viruses.