Virus cross-species transmission. Defining the immunological barriers to viral emergence

人类经常接触到各种动物病毒。了解为什么这些病毒中的大多数未能在人类群体中蔓延和蓬勃发展，对于制定管理病毒出现的最佳战略至关重要。我们的计划旨在了解病毒跨物种传播的不同免疫障碍。我们的假设是，每个个体或物种的遗传和免疫变异性有助于确定对病毒跨物种传播的易感性或抵抗力。我们的第一个目标是识别那些在病毒感染后立即激活的基因(称为干扰素刺激基因，ISGs)，并阻止呼吸道病毒。我们的第二个目标是建立一个风险评估框架，以确定那些有利于禽流感病毒向人类蔓延的特定病毒蛋白(以及蛋白中的特定氨基酸残基)。该计划的第三个也是最后一个目标是了解人类和选定动物物种中的抗体情况，以评估交叉中和抗体的影响，并在种群水平上估计交叉免疫对抑制病毒出现的影响。在该计划结束时，我们将能够通过提供可操作的数据来转化我们的发现，这些数据可以支持对病毒的人畜共患病潜力的风险评估。

Humans are constantly exposed to a variety of animal viruses. Understanding why most of these viruses fail to spillover and thrive in human populations is crucial to devise optimal strategies to manage viral emergence. Our programme aims to understand diverse immunological barriers to virus cross-species transmission. Our hypothesis is that the genetic and immunological variability of each individual or species helps define susceptibility or resistance to virus cross-species transmission. Our first aim is to identify those genes that are activated immediately after virus infection (known as interferon-stimulated genes, ISGs) and block respiratory viruses. Our second aim is to create a risk assessment framework to identify those specific viral proteins (and specific amino acid residues within the proteins) that favour the spillover of avian influenza viruses into the human population. The third and last aim of the programme is to understand the antibody landscape in humans and selected animal species, in order to estimate the impact of cross-neutralising antibodies and, at the population level, cross-immunity on constraining viral emergence. At the end of this programme, we will be able to translate our discoveries by delivering actionable data that can support the risk assessment of the zoonotic potential of viruses.