Amphotericin B increases influenza A virus infection by preventing IFITM3-mediated restriction.
Amphotericin B increases influenza A virus infection by preventing IFITM3-mediated restriction.
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DOI：
10.1016/j.celrep.2013.10.033
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发表时间：
2013-11-27
期刊：
影响因子：
8.8
通讯作者：
Brass AL
中科院分区：
文献类型：
--
作者：
Lin TY;Chin CR;Everitt AR;Clare S;Perreira JM;Savidis G;Aker AM;John SP;Sarlah D;Carreira EM;Elledge SJ;Kellam P;Brass AL
IFITM在体外和体内抑制甲型流感病毒（IAV）复制。在这里，我们建立了抗胸腺七肽，阿替西霉素B（两性B），防止IFITM 3介导的限制IAV，从而增加病毒复制。与其IFITM3的中和一致，AmphoB的临床制剂AmBisome在体外降低了干扰素对IAV的大部分保护作用。机制研究表明，IFITM 1降低宿主膜流动性，这表明IFITM介导的限制性的可能机制以及AmphoB对其的否定。值得注意的是，我们揭示了用AmBisome治疗的小鼠死于正常温和的IAV感染，类似于Ifitm3缺陷的动物。因此，接受AmphoB临床制剂抗真菌治疗的患者可能功能性免疫受损，因此更容易感染流感以及其他IFITM3限制性病毒感染。两性霉素B或AmBisome防止IFITM 3介导的IAV限制AmBisome克服IFN的大部分体外抗病毒作用IFITM 1降低膜流动性并抑制膜融合AmBisome增加流感的发病率和死亡率IFITM 3是一种广泛表达的抗病毒蛋白，其抑制多种人类致病病毒，包括甲型流感病毒（IAV）。Brass及其同事现在表明，一种广泛使用的抗真菌疗法AmBisome可以阻止IFITM3阻断IAV复制，并且给予AmBisome的小鼠会死于通常轻微的流感病毒感染。因此，接受AmBisome抗真菌治疗的患者可能在功能上免疫受损，因此更容易受到流感以及其他IFITM3限制性病毒感染的影响。
The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon’s protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections. Amphotericin B or AmBisome prevents IFITM3-mediated restriction of IAV AmBisome overcomes the majority of IFN’s antiviral effects in vitro IFITM1 decreases membrane fluidity and inhibits membrane fusion AmBisome increases the morbidity and mortality of influenza IFITM3 is a ubiquitously expressed antiviral protein that inhibits multiple human pathogenic viruses, including influenza A virus (IAV). Brass and colleagues now show that a widely used antifungal therapy, AmBisome, prevents IFITM3 from blocking IAV replication and that mice given AmBisome succumb to a normally mild influenza virus infection. Therefore, patients receiving antifungal therapy with AmBisome may be functionally immunocompromised and thus more vulnerable to influenza as well as other IFITM3-restricted viral infections.
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