A paucigranulocytic asthma host environment promotes the emergence of virulent influenza viral variants.
A paucigranulocytic asthma host environment promotes the emergence of virulent influenza viral variants.
复制标题
少粒细胞性哮喘宿主环境促进了强毒性流感病毒变体的出现。
DOI：
10.7554/elife.61803
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发表时间：
2021-02-16
期刊：
影响因子：
7.7
通讯作者：
Short KR
中科院分区：
文献类型：
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作者：
Hulme KD;Karawita AC;Pegg C;Bunte MJ;Bielefeldt-Ohmann H;Bloxham CJ;Van den Hoecke S;Setoh YX;Vrancken B;Spronken M;Steele LE;Verzele NA;Upton KR;Khromykh AA;Chew KY;Sukkar M;Phipps S;Short KR
流感病毒有很高的变异率，因此在一个宿主内可能会出现不同的病毒变种。有证据表明，由于干扰素反应受损，流感病毒变异体在孕妇和/或肥胖者中更为普遍。我们最近发现，非过敏性、少粒细胞哮喘亚型与I型干扰素的产生受损有关。在这里，我们试图解决这是否与流感病毒变异株的增加有关。与对照组相比，患有少粒细胞哮喘的小鼠疾病严重程度增加，流感病毒变异株增加。具体地说，仅在哮喘小鼠中检测到的PB1突变与聚合酶活性增加有关。此外，哮喘宿主衍生病毒导致野生型小鼠疾病严重程度增加。综上所述，这些数据表明，至少有一部分哮喘患者可能更容易感染严重流感，可能是新的流感病毒变种的一个可能来源。
Influenza virus has a high mutation rate, such that within one host different viral variants can emerge. Evidence suggests that influenza virus variants are more prevalent in pregnant and/or obese individuals due to their impaired interferon response. We have recently shown that the non-allergic, paucigranulocytic subtype of asthma is associated with impaired type I interferon production. Here, we seek to address if this is associated with an increased emergence of influenza virus variants. Compared to controls, mice with paucigranulocytic asthma had increased disease severity and an increased emergence of influenza virus variants. Specifically, PB1 mutations exclusively detected in asthmatic mice were associated with increased polymerase activity. Furthermore, asthmatic host-derived virus led to increased disease severity in wild-type mice. Taken together, these data suggest that at least a subset of patients with asthma may be more susceptible to severe influenza and may be a possible source of new influenza virus variants.