Foot-and-mouth disease virus replication in bovine epithelia and the relationship to cellular type/differentiation and cytopathology

口蹄疫病毒（FMDV）是一种高度传染性的疾病，可感染牛、羊和猪，在某些个体（仅反刍动物）中可导致持续感染，导致携带动物。携带者被定义为在暴露后28天以上可以从其上恢复活病毒的动物。大量实地证据表明，这些带菌者动物可能促成新的疾病爆发，它们的出现大大限制了易感活动物及其产品的贸易。口蹄疫仍然是对活动物和动物产品国际贸易的最重要限制。疾病的爆发使发展中国家无法进入利润丰厚的出口市场，而在已根除该疾病的发达国家，该疾病的再次出现仍可能造成毁灭性的经济后果，2001年英国的情况生动地证明了这一点。尽管它对动物健康有着深远的影响，但调节发病机制和持久性的因素仍然知之甚少。在口蹄疫的急性期，口蹄疫病毒迅速感染细胞，并在舌头和足部覆盖的皮肤上产生病变，皮肤上有一层死细胞。我们已经证明，从这些地点收集的样本含有最高水平的病毒。相比之下，即使有高水平的病毒，皮肤覆盖的喉咙和软腭也没有病变，没有死细胞层。此外，我们已经表明，口蹄疫病毒主要存在于更深层的皮肤组织的舌头和脚在疾病和软腭在持久性。尽管病毒存在于皮肤深层，但为什么病毒不能在软腭皮肤中产生病变的原因尚不清楚。软腭皮肤感染可能涉及病毒生长速度较慢，不会导致可观察到的病变。这可能是因为细胞处于不同的分裂或分化阶段，或者这些组织中的细胞是不同的。尽管这些都是有吸引力的可能性，但尚未进行旨在利用感染FMDV的动物回答这些问题的必要研究。因此，该提案旨在准确了解细胞类型，细胞状态，病毒生长和感染结果之间的关联。这可能揭示了为什么软腭不发生病变，并解释了为什么病毒在这种类型的皮肤中停留更长时间而不造成损害，而即使它已被损坏，也可以从其他皮肤中清除。

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease that can affect cattle, sheep and pigs, and in some individuals (ruminants only) it can cause persistent infections resulting in carrier animals. A carrier is defined as an animal from which live virus can be recovered for longer than 28 days after exposure. There is considerable field evidence to indicate that these carrier animals may precipitate new outbreaks of disease and their occurrence significantly constrains trade in live susceptible animals and their products. FMD remains the single most important constraint to international trade in live animals and animal products. Outbreaks prevent developing countries from gaining access to lucrative export markets and within the developed world where the disease has been eradicated the reappearance of the disease can still cause devastating economic consequences as was vividly demonstrated in the UK in 2001. Despite its profound impact on animal health, the factors that regulate pathogenesis and persistence are still poorly understood. During the acute phase of FMD, FMDV rapidly infects cells and produces lesions on the tongue and foot covered skin that has a layer of dead cells. We have shown that samples collected from these sites contain the highest levels of virus. In contrast, there are no lesions in the throat and soft palate covered by skin that has no layer of dead cells even when they have high levels of virus. In addition, we have shown that FMDV were predominantly present in the deeper layers of skin tissue of both tongue and foot during disease and in the soft palate during persistence. The reasons for why the virus cannot produce lesions in the soft palate skin despite their presence in the deep skin layer are not understood. It is possible that infection of the soft palate skin involves a slower rate of viral growth that does not lead to the production of observable lesions. This could be because the cells are at a different stage of division or differentiation or that the cells in these tissues are different. Even though these are attractive possibilities the necessary studies aimed at answering these questions using animals infected with FMDV have not been carried out. Therefore, this proposal seeks to understand precisely the association between cell type, cell status, virus growth and outcome of infection. This may reveal why lesions do not occur at the soft palate and provide an explanation as to why the virus remains in this type of skin for longer without causing damage while it can be cleared from other skin even though it has been damaged.