Foot-and-mouth disease virus entry: RNA release and membrane penetration

口蹄疫病毒(FMDV)是影响农业家畜的重要病原之一。它在世界大部分地区流行，特别是在发展中国家，它的存在限制了向无疾病国家出口动物产品的能力，因此对农村经济产生了不利影响。该病毒是已知的最具传染性的病原体之一，2001年在英国爆发的疫情充分证明了其造成经济和社会破坏的能力，该疫情使该国损失约100亿GB。口蹄疫病毒是微小核糖核酸病毒家族的成员，该家族还包括其他病毒，如脊髓灰质炎病毒和鼻病毒(普通感冒病毒)。在这类病毒的感染过程中，最不为人所知的步骤之一是病毒颗粒是如何“无涂层”的，并将其遗传物质(新病毒的蓝图)运输到细胞膜上以启动感染。我们一直在与其他实验室合作，使用脊髓灰质炎病毒(PV)研究这一过程，这种病毒是所有小核糖核酸病毒中最了解的。从这项工作中，关于光伏病毒如何实现感染过程的模型正在慢慢演变。它似乎是一种优雅而复杂的机制，涉及一系列中间粒子。然而，口蹄疫病毒颗粒与口蹄疫病毒具有非常不同的性质，在感染过程中表现出不同的行为，这使得将口蹄疫病毒模型外推到口蹄疫病毒是困难的。我们打算应用近年来开发的研究PV的新技术来详细研究口蹄疫病毒进入细胞的机制。这些方法使用人造类脂膜结构来模拟细胞膜，以便在实验室中对其进行精细控制和检测。我们将尝试使用这些系统模拟感染过程，并检查在病毒剥离过程中形成的中间结构及其对膜本身特性的影响。通过这种方式，我们希望深入了解病毒如何揭开其RNA基因组的外衣，并将其投射到人造细胞膜上。虽然这些研究具有直接的学术意义，但从长远来看，更好地理解感染过程也可能具有更大的实用价值。例如，感染过程中病毒结构的变化可能会暴露出改进疾病诊断或开发疫苗或抗病毒药物以阻断感染的新目标，就像艾滋病毒所显示的那样。

Foot-and-mouth disease virus (FMDV) is one of the most important pathogens affecting agricultural livestock. It is endemic in much of the world, especially in the developing world where its presence restricts the ability to export animal products to disease free countries and so adversely affects rural economies. The virus is one of the most infectious agents known and its ability to cause economic and social havoc was amply demonstrated by the outbreak in the UK in 2001 which cost the country ~£10 billion. FMDV is a member of the picornavirus family which includes other viruses such as poliovirus and rhinovirus (the common cold virus). One of the least well understood steps in the infection process by this family of viruses is how the virus particle is 'uncoated' and transports its genetic material (the blueprint for new virus) across the cell membrane to initiate an infection. We have been studying this process, in collaboration with other laboratories, using poliovirus (PV), which is the best understood of all picornaviruses. From this work, a model of how the infection process is achieved by PV is slowly evolving. It appears to be an elegant and sophisticated mechanism involving a series of intermediate particles. However, FMDV particles are known to have very different properties to those of PV and appear to behave differently during the infection process and this makes it difficult to extrapolate the PV model to FMDV. We intend to apply the novel techniques that we have developed in recent years for studying PV to investigate in detail the mechanism of cell entry by FMDV. These methods use artificial lipid membrane structures to mimic cellular membranes in such a way that they can be finely controlled and examined in the laboratory. We will attempt to mimic the infectious process using these systems and examine the intermediate structures formed during the uncoating of the virus and their effects on the properties of the membranes themselves. In this way we hope to gain insight into how the virus uncoats and projects its RNA genome across an artificial equivalent of a cell membrane. Although these studies are of immediate academic interest, a better understanding of the infection process may also have more practical value in the longer term. For example, alterations in virus structure during the infection process may expose new targets for improved diagnosis of the disease or for the development of vaccines or antiviral drugs to block infection, as has been shown for HIV.