Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, Singapore, 117549, Singapore.
Bull Math Biol. 2024 Jun 9;86(7):85. doi: 10.1007/s11538-024-01305-0.
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.
病毒感染的发展方式可能因最初进入体内的病毒数量而异。由于具有挑战性的限制和缺乏研究，人们对感染剂量的影响仍不完全了解。关于麻疹病毒（MV），获得更多的见解至关重要。MV 感染剂量越高，急性病毒血症的峰值出现得越早，但病毒血症峰值的幅度几乎保持不变。麻疹具有高度传染性，会导致免疫抑制，如淋巴细胞减少，并在很大程度上导致儿童发病率和死亡率上升。这项工作研究了观察到的食蟹猴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对病毒血症的纵向数据进行了拟合，并使用赤池信息量准则（AIC）来评估相关的生物学假设及其各自的模型参数化。AIC 值最低表示感染剂量、初始病毒载量和初始活化的 MV 特异性 T 细胞数量之间存在线性关系。早期病毒血症峰值与高初始活化的 MV 特异性 T 细胞数量相关。因此，当 MV 感染剂量增加时，初始病毒血症和相关免疫细胞刺激增加，从而减少 T 细胞杀伤足以发挥作用所需的时间，从而使病毒血症、MV 特异性 T 细胞和淋巴细胞耗竭出现与剂量无关的峰值。总之，这些结果表明麻疹的发展取决于病毒和宿主在感染初期的相互作用以及细胞免疫对病毒的控制效率。这些关系为麻疹的预防、疫苗接种和早期治疗提供了额外的动力。
