Pulmonary surfactant lipids inhibit infections with the pandemic H1N1 influenza virus in several animal models
Pulmonary surfactant lipids inhibit infections with the pandemic H1N1 influenza virus in several animal models
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DOI：
10.1074/jbc.ra119.012053
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发表时间：
2020-02-07
影响因子：
4.8
通讯作者：
Voelker, Dennis R.
中科院分区：
文献类型：
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作者：
Numata, Mari;Mitchell, James R.;Voelker, Dennis R.
2009年爆发的甲型H1N1流感pdm 09证明了伴随新型甲型流感病毒（IAV）毒株出现的问题及其在没有预先存在免疫力的人群中的意外毒力。神经氨酸酶抑制剂（NAIs）目前是干预IAV爆发的首选药物，但人们担心NAI耐药病毒会传播给高危人群。这些问题突出表明，需要采取新的方法来解决每年的流感负担。在这项研究中，我们研究了棕榈酰-油酰-磷脂酰甘油（POPG）和磷脂酰肌醇（PI）是否有效地拮抗（H1N1）pdm 09感染。POPG和PI显着抑制（H1N1）pdm 09感染的Madin-Darby犬肾细胞中的细胞病变效应和减弱病毒基因表达。POPG和PI以高亲和力与（H1N1）pdm 09结合，并在组织培养中破坏病毒从感染细胞向未感染细胞的传播，并且在体外建立病毒感染后还将（H1N1）pdm 09的传播减少10（2）倍。在（H1N1）pdm 09的小鼠感染模型中，POPG和PI显著降低肺部炎症和病毒负荷。值得注意的是，当用典型致死剂量的1000空斑形成单位的（H1N1）pdm 09攻击小鼠时，与没有这种治疗的0%（14只小鼠中的0只）相比，用POPG治疗10天后的存活率为100%（14只小鼠中的14只）。在雪貂模型中，POPG还显著降低了由（H1N1）pdm 09感染诱导的炎性浸润和病毒负荷。这些发现表明，阴离子磷脂在动物模型中有力且有效地破坏流感感染。
The influenza A (H1N1)pdm09 outbreak in 2009 exemplified the problems accompanying the emergence of novel influenza A virus (IAV) strains and their unanticipated virulence in populations with no pre-existing immunity. Neuraminidase inhibitors (NAIs) are currently the drugs of choice for intervention against IAV outbreaks, but there are concerns that NAI-resistant viruses can transmit to high-risk populations. These issues highlight the need for new approaches that address the annual influenza burden. In this study, we examined whether palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI) effectively antagonize (H1N1)pdm09 infection. POPG and PI markedly suppressed cytopathic effects and attenuated viral gene expression in (H1N1)pdm09-infected Madin-Darby canine kidney cells. POPG and PI bound to (H1N1)pdm09 with high affinity and disrupted viral spread from infected to noninfected cells in tissue culture and also reduced (H1N1)pdm09 propagation by a factor of 10(2) after viral infection was established in vitro. In a mouse infection model of (H1N1)pdm09, POPG and PI significantly reduced lung inflammation and viral burden. Of note, when mice were challenged with a typically lethal dose of 1000 plaque-forming units of (H1N1)pdm09, survival after 10 days was 100% (14 of 14 mice) with the POPG treatment compared with 0% (0 of 14 mice) without this treatment. POPG also significantly reduced inflammatory infiltrates and the viral burden induced by (H1N1)pdm09 infection in a ferret model. These findings indicate that anionic phospholipids potently and efficiently disrupt influenza infections in animal models.