Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window
Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window
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DOI：
10.1099/jgv.0.000584
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发表时间：
2016-10-01
影响因子：
3.8
通讯作者：
Shelton, Holly
中科院分区：
文献类型：
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作者：
James, Joe;Howard, Wendy;Shelton, Holly
在禽流感流行的地理区域，禽流感是家禽业的重大经济负担。当禽流感亚型感染人类时，它也会引起公共卫生问题，通常死亡率很高。了解对甲型流感病毒（IAV）适应性（感染性、传播和致病性）有积极贡献的病毒遗传因素对人类和牲畜健康都非常重要。PB1-F2是由IAV编码的小辅助蛋白，并且在哺乳动物宿主中已经涉及有助于增加致病性的广泛功能。在禽类宿主中，尽管在禽类IAV分离株中具有高水平的全长保守性，但该蛋白质尚未得到充分研究，这与在哺乳动物宿主分离株中经常发现的PB1-F2长度的截短形成对比。在这里，我们报告了一个全长PB1-F2蛋白的存在，从低致病性H9N2禽流感病毒，阻止感染性病毒脱落直接接种鸡，从而提高了通过延长传播窗口接触鸟类的病毒的传播。除了延长传播外，全长PB1-F2的存在还抑制了致病性，其证据是与缺乏PB1-F2 ORF的病毒相比，含胚鸡蛋中的最小致死剂量增加，直接感染鸟类的存活率增加。我们认为，在感染鸟类宿主后，存在维持全长功能性PB 1-F2蛋白的正压力，因为它有助于IAV在田间的有效传播。
Avian influenza is a significant economic burden on the poultry industry in geographical regions where it is enzootic. It also poses a public health concern when avian influenza subtypes infect humans, often with high mortality. Understanding viral genetic factors which positively contribute to influenza A virus (IAV) fitness - infectivity, spread and pathogenesis - is of great importance both for human and livestock health. PB1-F2 is a small accessory protein encoded by IAV and in mammalian hosts has been implicated in a wide range of functions that contribute to increased pathogenesis. In the avian host, the protein has been understudied despite high-level full-length conservation in avian IAV isolates, which is in contrast to the truncations of the PB1-F2 length frequently found in mammalian host isolates. Here we report that the presence of a full-length PB1-F2 protein, from a low pathogenicity H9N2 avian influenza virus, prolongs infectious virus shedding from directly inoculated chickens, thereby enhancing transmission of the virus by lengthening the transmission window to contact birds. As well as extending transmission, the presence of a full-length PB1-F2 suppresses pathogenicity evidenced by an increased minimum lethal dose in embryonated chicken eggs and increasing survival in directly infected birds when compared to a virus lacking an ORF for PB1-F2. We propose that there is a positive pressure to maintain a full-length functional PB1-F2 protein upon infection of avian hosts as it contributes to the effective transmission of IAV in the field.