PDF(Pubmed)
Abstract：
How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains incomplete, in part due to challenging constraints, and a lack of research. Gaining more insights is crucial regarding the measles virus (MV). The higher the MV infection dose, the earlier the peak of acute viremia, but the magnitude of the peak viremia remains almost constant. Measles is highly contagious, causes immunosuppression such as lymphopenia, and contributes substantially to childhood morbidity and mortality. This work investigated mechanisms underlying the observed wild-type measles infection dose responses in cynomolgus monkeys. We fitted longitudinal data on viremia using maximum likelihood estimation, and used the Akaike Information Criterion (AIC) to evaluate relevant biological hypotheses and their respective model parameterizations. The lowest AIC indicates a linear relationship between the infection dose, the initial viral load, and the initial number of activated MV-specific T cells. Early peak viremia is associated with high initial number of activated MV-specific T cells. Thus, when MV infection dose increases, the initial viremia and associated immune cell stimulation increase, and reduce the time it takes for T cell killing to be sufficient, thereby allowing dose-independent peaks for viremia, MV-specific T cells, and lymphocyte depletion. Together, these results suggest that the development of measles depends on virus-host interactions at the start and the efficiency of viral control by cellular immunity. These relationships are additional motivations for prevention, vaccination, and early treatment for measles.
摘要：
病毒感染的发展方式可以根据最初进入体内的病毒数量而改变。对感染剂量的影响的理解仍然不完整，部分是由于具有挑战性的限制，缺乏研究。获得更多的见解对于麻疹病毒（MV）至关重要。MV感染剂量越高，急性病毒血症的高峰越早，但是病毒血症高峰的幅度几乎保持不变。麻疹具有高度传染性,导致免疫抑制，如淋巴细胞减少，并对儿童发病率和死亡率做出了重大贡献。这项工作研究了食蟹猴中观察到的野生型麻疹感染剂量反应的潜在机制。我们使用最大似然估计拟合病毒血症的纵向数据，并使用Akaike信息准则(AIC)评估相关生物学假设及其各自的模型参数化。最低的AIC表示感染剂量之间的线性关系，最初的病毒载量，和激活的MV特异性T细胞的初始数量。早期峰值病毒血症与活化的MV特异性T细胞的高初始数量相关。因此，当MV感染剂量增加时，初始病毒血症和相关的免疫细胞刺激增加，并减少T细胞杀伤所需的时间，从而允许病毒血症的剂量非依赖性峰值，MV特异性T细胞,和淋巴细胞耗竭。一起,这些结果表明，麻疹的发展取决于病毒与宿主在开始时的相互作用以及通过细胞免疫控制病毒的效率。这些关系是预防的额外动机，疫苗接种,和麻疹的早期治疗。
