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Comprehensive mapping of rhadinovirus dissemination and persistence

病毒传播和持久性的综合绘图

基本信息

批准号：
BB/J014419/1
负责人：
Colin Crump
金额：
$ 60.07万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FJ014419%2F1
关键词：
Comprehensive mapping rhadinovirus dissemination persistence

项目摘要

Rhadinoviruses infect both man and economically important animals. Infection predisposes to several cancers, and even though these are individually uncommon the high prevalence of infection leads to a large total disease burden, particularly in the developing world. For example Kaposi's Sarcoma is the commonest cancer in untreated HIV infection and is caused by a rhadinovirus. Once rhadinoviruses infect they persist lifelong and spread to close contacts. However, surprisingly little is known about how and where in the body they persist. White blood cells are one site but there also appear to be other sites that are important for disease. The lack of complete information makes it very difficult to develop infection control measures such as vaccination. Large animal and human rhadinoviruses are difficult to study. However, all mammals carry their own related viruses that behave in broadly similar ways. Mice provide the standard experimental model of mammalian biology, and so by studying a murine rhadinovirus - MuHV-4 - we can go a long way to understanding how these viruses as a whole work. Here we will use MuHV-4 to establish where in the body persistent infection is established, how it gets there from the point of virus entry, and how it then gets back to the sites from which virus is released to infect new hosts. Rhadinoviruses can exist in either lytic or latent forms. When lytic they produce new virus, but are vulnerable to attack; when latent they are relatively inactive and so difficult to attack. Persistent infection is predominantly latent. However, lytic replication is required for virus to spread between different cell types, and this seems to be essential for normal infection. By defining precisely where lytic replication is essential we can identify targets for therapeutic intervention. Thus we can start to develop new means of reducing human and animal disease.

狂犬病病毒感染人类和重要的经济动物。感染易导致几种癌症，尽管这些癌症个别并不常见，但感染的高流行率导致了巨大的总疾病负担，特别是在发展中国家。例如，在未经治疗的艾滋病毒感染中，卡波西氏肉瘤是最常见的癌症，是由一种狂犬病病毒引起的。弹状病毒一旦感染，就会持续终生，并向密切接触者传播。然而，令人惊讶的是，人们对它们如何在体内以及在哪里持续存在知之甚少。白血球是一个部位，但似乎还有其他对疾病很重要的部位。由于缺乏完整的信息，很难制定疫苗接种等感染控制措施。大型动物和人类杆状病毒很难研究。然而，所有哺乳动物都携带着它们自己的相关病毒，这些病毒的行为方式大致相似。小鼠提供了哺乳动物生物学的标准实验模型，因此通过研究小鼠流感病毒-MuHV-4-我们可以在很大程度上了解这些病毒作为一个整体是如何工作的。在这里，我们将使用MuHV-4来确定在体内的哪里建立持续感染，它是如何从病毒进入点到达那里的，然后它如何回到释放病毒的地点感染新的宿主。流行性感冒病毒既可以是裂解的，也可以是潜伏的。当裂解时，它们会产生新的病毒，但容易受到攻击；当潜伏时，它们相对不活跃，因此很难攻击。持续性感染主要是潜伏性的。然而，病毒需要裂解复制才能在不同类型的细胞之间传播，这似乎是正常感染所必需的。通过准确地确定裂解复制在哪里是必不可少的，我们可以确定治疗干预的靶点。因此，我们可以开始开发减少人类和动物疾病的新方法。