Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation.
Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation.
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DOI：
10.1038/srep17999
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发表时间：
2015-12-08
影响因子：
4.6
通讯作者：
Chang KC
中科院分区：
文献类型：
--
作者：
Chang P;Kuchipudi SV;Mellits KH;Sebastian S;James J;Liu J;Shelton H;Chang KC
猪对禽流感病毒的抵抗力明显强于猪流感病毒，部分是通过前线上皮细胞和肺泡巨噬细胞（AM）介导的。虽然猪AM（PAM）在流感病毒控制中至关重要，但其控制模式尚不清楚。为了深入了解PAM在介导禽流感病毒抗性中的可能作用，我们比较了两种禽流感病毒（H2 N3和H6 N1）和三种哺乳动物流感病毒（猪H1N1、人H1N1和大流行性H1N1）在PAM中的宿主效应和复制。我们发现，PAM容易对所有五种禽流感和哺乳动物流感病毒的初始感染敏感，但只有禽流感病毒引起早期和广泛的细胞凋亡（感染6小时），导致病毒后代减少和促炎症作用减弱。全长病毒PB 1-F2只存在于禽流感病毒是一种毒力因子，其靶向AM进行与细胞凋亡相关的细胞死亡。通过对禽H5 N1病毒的反向遗传学的使用，我们发现全长PB 1-F2有助于增加细胞凋亡和促炎症，但不减少病毒复制。综上所述，我们认为PAM的早期凋亡限制了禽流感病毒的传播，而PB 1-F2可能在这一过程中发挥了重要作用。
Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) influenza viruses in PAM. We found that PAM were readily susceptible to initial infection with all five avian and mammalian influenza viruses but only avian viruses caused early and extensive apoptosis (by 6 h of infection) resulting in reduced virus progeny and moderated pro-inflammation. Full length viral PB1-F2 present only in avian influenza viruses is a virulence factor that targets AM for mitochondrial-associated apoptotic cell death. With the use of reverse genetics on an avian H5N1 virus, we found that full length PB1-F2 contributed to increased apoptosis and pro-inflammation but not to reduced virus replication. Taken together, we propose that early apoptosis of PAM limits the spread of avian influenza viruses and that PB1-F2 could play a contributory role in the process.