Viral Pathogenesis and Regulation Mechanism of Free Radicals in Host Responses : Role of Nitric Oxide

迄今为止，自由基分子物种在各种病毒性疾病发病机制中的重要性已日益被认识到。另一类简单无机自由基一氧化氮（NO）在病毒感染的宿主防御机制和发病机制中受到了相当大的关注。现在有充分的证据表明，NO合成途径，特别是NO合成酶（iNOS）的诱导异构体，通过诱导促炎细胞因子如干扰素- γ和白细胞介素-1 - β，在不同的病毒疾病中表达。近年来的研究表明，一氧化氮与过量产生的氧自由基，特别是超氧化物（O_2）在宿主对抗各种入侵微生物的炎症反应中起着重要作用。过氧亚硝酸盐是一种在生物系统中由NO与O_2反应而产生的高活性氮氧化物。本课题研究NO在流感病毒和单纯疱疹病毒感染动物模型发病机制中的作用。因此，我们发现了一个令人信服的证据，即过氧亚硝酸盐的形成在小鼠流感病毒感染的发病机制中起关键作用。因此，了解NO与病毒感染中产生的氧自由基的作用将为病毒的发病机制提供新的见解。更重要的是，一种通过调节自由基生成来治疗人类各种病毒性疾病的新方法可能成为可能。

To date, importance of free radical molecular species in the pathogenesis of various viral diseases has been increasingly recognized. Considerable attenstion is given to another type of simple inorganic radical nitric oxide (NO) in the host defense mechanism and pathogenesis of virus infection. It is now well documented that NO synthesis pathway in particular inducible isoform of NO synthase (iNOS) is expressed in different array of virus diseases via induction of proinflammatory cytokines such as interferon-gamma, and interleukin-1beta. Recent studies indicate that NO together with oxygen radicals particularly superoxide (O_2) produced excessively play an important role in inflammatory response of the host against various intruding microbes. A highly reactive nitrogen oxide species peroxynitrite is produced in biological systems through the reaction of NO with O_2. In this research project, role of NO in the pathogenesis of animal models of influenza virus and herpes simplex virus infections was investigated. As a results, we found a convincing evidence that formation of peroxynitrite is critically involved in the pathogenesis of influenza virus infection in mice. Thus, understanding of the role of NO in conjunction with oxygen radicals generated in virus infectionswill provide a new insight into the viral pathogenesis. More importantly, a novel therapeutic approach by regulating the free radical generation may be possible in various viral diseases in humans.