Staphylococcus aureus Lipase 1 Enhances Influenza A Virus Replication
Staphylococcus aureus Lipase 1 Enhances Influenza A Virus Replication
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DOI：
10.1128/mbio.00975-20
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发表时间：
2020-07-01
期刊：
影响因子：
6.4
通讯作者：
Fitzgerald, J. Ross
中科院分区：
文献类型：
--
作者：
Goncheva, Mariya, I;Conceicao, Carina;Fitzgerald, J. Ross
甲型流感病毒（IAV）每年在人类中引起呼吸道疾病的流行，通常伴有与细菌病原体如金黄色葡萄球菌的继发性合并感染。在这里，我们报告说，S。金黄色葡萄球菌分泌的蛋白脂肪酶1在体外增强IAV在原代细胞（包括人肺成纤维细胞）中的复制。脂肪酶1的前病毒活性取决于其酶功能，在病毒生命周期的后期起作用，并通过正调节病毒出芽导致感染性增加。此外，脂肪酶1对IAV的前病毒作用在含胚鸡蛋的体内感染期间表现出来，并且重要的是，将IAV疫苗株的产量增加约5倍。因此，我们已经确定了第一个S。金黄色葡萄球菌蛋白增强IAV复制，表明在共同感染中的潜在作用。重要的是，这一活动可用于解决全球流感疫苗短缺的问题。重要性甲型流感病毒（IAV）可引起呼吸道疾病的年度流行和散发性大流行。继发性细菌合并感染的有机体，如金黄色葡萄球菌是最常见的并发症的原发性IAV感染，并与高水平的发病率和死亡率。在这里，我们报告了第一个确定的S。一种金黄色葡萄球菌因子（脂肪酶1），在感染过程中通过对病毒出芽的积极调节来增强IAV复制。在鸡胚的体内观察到这种效果，并大大提高了疫苗株的产量，这一发现可用于解决全球流感疫苗短缺的问题。
Influenza A virus (IAV) causes annual epidemics of respiratory disease in humans, often complicated by secondary coinfection with bacterial pathogens such as Staphylococcus aureus. Here, we report that the S. aureus secreted protein lipase 1 enhances IAV replication in vitro in primary cells, including human lung fibroblasts. The proviral activity of lipase 1 is dependent on its enzymatic function, acts late in the viral life cycle, and results in increased infectivity through positive modulation of virus budding. Furthermore, the proviral effect of lipase 1 on IAV is exhibited during in vivo infection of embryonated hen's eggs and, importantly, increases the yield of a vaccine strain of IAV by approximately 5-fold. Thus, we have identified the first S. aureus protein to enhance IAV replication, suggesting a potential role in coinfection. Importantly, this activity may be harnessed to address global shortages of influenza vaccines.IMPORTANCE Influenza A virus (IAV) causes annual epidemics and sporadic pandemics of respiratory disease. Secondary bacterial coinfection by organisms such as Staphylococcus aureus is the most common complication of primary IAV infection and is associated with high levels of morbidity and mortality. Here, we report the first identified S. aureus factor (lipase 1) that enhances IAV replication during infection via positive modulation of virus budding. The effect is observed in vivo in embryonated hen's eggs and greatly enhances the yield of a vaccine strain, a finding that could be applied to address global shortages of influenza vaccines.