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

牛上皮细胞中的口蹄疫病毒复制及其与细胞类型/分化和细胞病理学的关系

• 批准号: BB/E003435/1
• 负责人: Bryan Charleston
• 金额: $ 61.69万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE003435%2F1
• 关键词: Foot; mouth; disease; virus; replication

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.

口蹄疫病毒 (FMDV) 会引起一种高度传染性疾病，可影响牛、羊和猪，在某些个体（仅限反刍动物）中，它可引起持续感染，从而导致带菌动物。携带者被定义为在接触后超过 28 天可以从其中恢复活病毒的动物。有大量现场证据表明，这些携带动物可能会引发新的疾病爆发，并且它们的发生严重限制了活体易感动物及其产品的贸易。口蹄疫仍然是活体动物和动物产品国际贸易的最重要的制约因素。疫情使发展中国家无法进入利润丰厚的出口市场，而在该疾病已被根除的发达国家，该疾病的再次出现仍可能造成毁灭性的经济后果，2001 年英国就生动地证明了这一点。尽管它对动物健康产生了深远影响，调节发病机制和持续性的因素仍然知之甚少。在口蹄疫急性期，口蹄疫病毒会迅速感染细胞，并在舌头和足部覆盖的皮肤上产生病变，并有一层死细胞。我们已经表明，从这些站点收集的样本中病毒含量最高。相比之下，即使病毒水平很高，被没有死细胞层的皮肤覆盖的喉咙和软腭也没有病变。此外，我们还发现，口蹄疫病毒在疾病期间主要存在于舌头和足部皮肤组织的深层，在持续期间则主要存在于软腭。尽管病毒存在于深层皮肤层，但其无法在软腭皮肤中产生病变的原因尚不清楚。软腭皮肤感染可能会导致病毒生长速度减慢，但不会导致产生明显的病变。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不同。尽管这些可能性很有吸引力，但尚未利用感染口蹄疫的动物进行旨在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会出现病变，并解释了为什么病毒在这种类型的皮肤中保留更长时间而不会造成损害，而即使其他皮肤受到损害，它也可以从其他皮肤中清除。

项目成果

Dynamics of foot-and-mouth disease virus replication in cells at different phases of the cell-division cycle

细胞分裂周期不同阶段的细胞内口蹄疫病毒复制动态

• DOI: http://dx.10.15302/j-fase-2014031
• 发表时间: 2014
• 期刊: Frontiers of Agricultural Science and Engineering
• 影响因子: 3.7
• 作者: BASHIRUDDIN J

Cytokine mRNA responses in bovine epithelia during foot-and-mouth disease virus infection.

口蹄疫病毒感染期间牛上皮细胞因子 mRNA 反应。

• DOI: http://dx.10.1016/j.tvjl.2007.08.012
• 发表时间: 2009
• 期刊: 1997)
• 作者: Zhang Z