Influenza A virus NS1 proteins and the control of pulmonary ion transport

甲型流感病毒可以在世界范围内流行，通过肺损伤和肺部泛滥导致数百万人死亡。肺液超载通常是通过肺内膜中的分子泵连接到由信号分子(包括酶PI3K)控制的钠渗透通道来防止的。甲型流感病毒在受感染的细胞中产生一种蛋白质，称为NS1，这是病毒毒力的重要决定因素。的确，禽流感？目前在东南亚传播的这种病毒对人类健康构成危险，因为这种病毒编码的一种NS1蛋白与正常流感病毒中发现的略有不同。如果我们要为这种危险的病毒开发新的治疗方法，那么重要的是了解流感病毒NS1蛋白可以改变受感染细胞的生理特性的方式。最近发表的工作表明，Ns1可以增加宿主细胞中PI3K的活性，申请人S实验室的工作表明，Ns1也可以通过PI3K依赖和非依赖途径增加钠通道的通透性。通过证明NS1可以改变感染细胞的特性，我们发现了NS1蛋白的一种全新的功能，研究的目的是确定这种蛋白可以以何种方式干扰肺/呼吸道上皮细胞的功能。因此，这些研究提供的数据可能会通过揭示允许这些病毒扰乱肺功能的机制来改进流感的治疗方法。

Influenza A viruses can world-wide pandemics resulting in millions of deaths through lung damage and flooding of the lungs. Lung fluid overload is normally prevented by molecular pumps in the lung lining linked to sodium permeable channels controlled by signalling molecules, including the enzyme, PI3K. Influenza A viruses make a protein, termed NS1, in infected cells that is an important determinant of viral virulence. Indeed, the ?bird ?flu? which currently circulates in SE Asia is dangerous to human health because this virus strain encodes a form of the NS1 protein that differs slightly from that found in normal flu viruses. If we are to develop new treatements for such dangerous viruses, then it is important to understand the ways in which the influenza virus NS1 proteins can alter the physiological properties of the infected cell. Recently published work showed that NS1 could increase the activity of PI3K in the host cell, and work from the applicant?s laboratory showed that NS1 can also increase sodium channel permeability by both PI3K-dependent and -independent pathways. By showing that NS1 can alter the properties of infected cells we have discovered an entirely novel function for the NS1 protein and the purpose of the study is to identify ways in which this protein can disturb the functioning of the lung / airway epithelia. The data provided by these studies may therefore lead to improved treatments for influenza by revealing the mechanisms that allow these viruses to disrupt lung function.