Deventhiran Jagadeeswaran, Kumar Sandeep R P, Raghunath Shobana, Leroith Tanya, Elankumaran Subbiah
Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA.
Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA
J Virol. 2015 Oct 14;90(1):222-31. doi: 10.1128/JVI.01551-15. Print 2016 Jan 1.
PB1-F2 protein, the 11th influenza A virus (IAV) protein, is considered to play an important role in primary influenza virus infection and postinfluenza secondary bacterial pneumonia in mice. The functional role of PB1-F2 has been reported to be a strain-specific and host-specific phenomenon. Its precise contribution to the pathogenicity and transmission of influenza virus in mammalian host, such as swine, and avian hosts, such as turkeys, remain largely unknown. In this study, we explored the role of PB1-F2 protein of triple-reassortant (TR) H3N2 swine influenza virus (SIV) in pigs and turkeys. Using the eight-plasmid reverse genetics system, we rescued wild-type SIV A/swine/Minnesota/1145/2007 (H3N2) (SIV 1145-WT), a PB1-F2 knockout mutant (SIV 1145-KO), and its N66S variant (SIV 1145-N66S). The ablation of PB1-F2 in SIV 1145 modulated early-stage apoptosis but did not affect the viral replication in swine alveolar macrophage cells. In pigs, PB1-F2 expression did not affect nasal shedding, lung viral load, immunophenotypes, and lung pathology. On the other hand, in turkeys, SIV 1145-KO infected poults, and its in-contacts developed clinical signs earlier than SIV 1145-WT groups and also displayed more extensive histopathological changes in intestine. Further, turkeys infected with SIV 1145-N66S displayed poor infectivity and transmissibility. The more extensive histopathologic changes in intestine and relative transmission advantage observed in turkeys infected with SIV 1145-KO need to be further explored. Taken together, these results emphasize the host-specific roles of PB1-F2 in the pathogenicity and transmission of IAV.
Novel triple-reassortant H3N2 swine influenza virus emerged in 1998 and spread rapidly among the North American swine population. Subsequently, it showed an increased propensity to reassort, generating a range of reassortants. Unlike classical swine influenza virus, TR SIV produces a full-length PB1-F2 protein, which is considered an important virulence marker of IAV pathogenicity. Our study demonstrated that the expression of PB1-F2 does not impact the pathogenicity of TR H3N2 SIV in pigs. On the other hand, deletion of PB1-F2 caused TR H3N2 SIV to induce clinical disease early and resulted in effective transmission among the turkey poults. Our study emphasizes the continuing need to better understand the virulence determinants for IAV in intermediate hosts, such as swine and turkeys, and highlights the host-specific role of PB1-F2 protein.
PB1-F2蛋白是甲型流感病毒（IAV）的第11种蛋白，被认为在小鼠原发性流感病毒感染和流感后继发性细菌性肺炎中起重要作用。据报道，PB1-F2的功能作用是一种毒株特异性和宿主特异性现象。其对流感病毒在哺乳动物宿主（如猪）和禽类宿主（如土耳其）的致病性和传播的确切贡献在很大程度上仍不清楚。在本研究中，我们探讨了三重重配（TR）H3N2猪流感病毒（SIV）的PB1-F2蛋白在猪和土耳其中的作用。使用八质粒反向遗传学系统，我们拯救了野生型SIV A/猪/明尼苏达/1145/2007（H3N2）（SIV 1145-WT）、PB1-F2敲除突变体（SIV 1145-KO）及其N66S变体（SIV 1145-N66S）。SIV 1145中PB1-F2的缺失调节了早期细胞凋亡，但不影响猪肺泡巨噬细胞中的病毒复制。在猪中，PB1-F2的表达不影响鼻内排毒、肺病毒载量、免疫表型和肺病理学。另一方面，在土耳其，SIV 1145-KO感染了小火鸡，其接触者比SIV 1145-WT组更早出现临床症状，并且在肠道中也表现出更广泛的组织病理学变化。此外，感染SIV 1145-N66S的土耳其表现出较差的感染性和传播性。感染SIV 1145-KO的土耳其中观察到的肠道中更广泛的组织病理学变化和相对传播优势需要进一步探索。综上所述，这些结果强调了PB1-F2在IAV致病性和传播中的宿主特异性作用。
新型三重重配H3N2猪流感病毒于1998年出现，并在北美猪群中迅速传播。随后，它表现出更高的重配倾向，产生了一系列重配体。与经典猪流感病毒不同，TR SIV产生全长PB1-F2蛋白，该蛋白被认为是IAV致病性的重要毒力标志物。我们的研究表明，PB1-F2的表达不影响TR H3N2 SIV在猪中的致病性。另一方面，PB1-F2的缺失导致TR H3N2 SIV早期诱导临床疾病，并在小火鸡之间有效传播。我们的研究强调了继续需要更好地了解IAV在中间宿主（如猪和土耳其）中的毒力决定因素，并突出了PB1-F2蛋白的宿主特异性作用。
