Increased inducible nitric oxide synthase expression in organs is associated with a higher severity of H5N1 influenza virus infection.
Increased inducible nitric oxide synthase expression in organs is associated with a higher severity of H5N1 influenza virus infection.
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DOI：
10.1371/journal.pone.0014561
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发表时间：
2011-01-19
期刊：
影响因子：
3.7
通讯作者：
Bean AG
中科院分区：
文献类型：
--
作者：
Burggraaf S;Bingham J;Payne J;Kimpton WG;Lowenthal JW;Bean AG
H5N1流感病毒感染引起疾病严重程度的机制仍不清楚。研究表明，高病毒载量和相关的高炎症免疫应答在感染发作期间是有影响的。这种失调的炎症反应与增加的自由基水平，如一氧化氮（NO），似乎可能有助于疾病的严重程度。然而，一氧化氮合酶（NOS）家族的酶如NOS的诱导型（iNOS）产生NO，其作为有效的抗病毒分子与急性期蛋白和细胞因子组合以对抗感染。然而，在H5N1感染期间过度产生iNOS和随后的高水平NO可能具有负面影响，与其他破坏性氧化剂一起作用以促进过度炎症或诱导细胞凋亡。感染H5N1流感后，鸡和鸭之间的疾病严重程度存在显著差异。鸡表现出高水平的死亡率和相关的病理学，而鸭表现出相对较轻的症状。目前尚不清楚这种不同的致病性是如何产生的，尽管有人认为，与鸭的反应相比，鸡对感染的过度活跃的炎症免疫反应可能是造成观察到的病理学差异的原因。在这项研究中，我们确定和调查诱导型一氧化氮合酶基因表达在鸭和鸡在H5N1流感感染。感染鸡在广泛的器官中显示iNOS表达的显着增加。相比之下，感染的鸭组织具有较低的组织相关的iNOS表达水平。在H5N1禽流感感染期间在鸡和鸭之间观察到的iNOS表达水平的差异可能在促成病理学的炎症反应中是重要的。了解H5N1流感病毒感染过程中iNOS的表达调控及其作用，可能为禽流感病毒感染的治疗提供新的思路。
The mechanisms of disease severity caused by H5N1 influenza virus infection remain somewhat unclear. Studies have indicated that a high viral load and an associated hyper inflammatory immune response are influential during the onset of infection. This dysregulated inflammatory response with increased levels of free radicals, such as nitric oxide (NO), appears likely to contribute to disease severity. However, enzymes of the nitric oxide synthase (NOS) family such as the inducible form of NOS (iNOS) generate NO, which serves as a potent anti-viral molecule to combat infection in combination with acute phase proteins and cytokines. Nevertheless, excessive production of iNOS and subsequent high levels of NO during H5N1 infection may have negative effects, acting with other damaging oxidants to promote excessive inflammation or induce apoptosis. There are dramatic differences in the severity of disease between chickens and ducks following H5N1 influenza infection. Chickens show a high level of mortality and associated pathology, whilst ducks show relatively minor symptoms. It is not clear how this varying pathogenicty comes about, although it has been suggested that an overactive inflammatory immune response to infection in the chicken, compared to the duck response, may be to blame for the disparity in observed pathology. In this study, we identify and investigate iNOS gene expression in ducks and chickens during H5N1 influenza infection. Infected chickens show a marked increase in iNOS expression in a wide range of organs. Contrastingly, infected duck tissues have lower levels of tissue related iNOS expression. The differences in iNOS expression levels observed between chickens and ducks during H5N1 avian influenza infection may be important in the inflammatory response that contributes to the pathology. Understanding the regulation of iNOS expression and its role during H5N1 influenza infection may provide insights for the development of new therapeutic strategies in the treatment of avian influenza infection.
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