Lloyd A L
Program in Theoretical Biology, Institute for Advanced Study, Princeton, NJ 08540, USA.
Proc Biol Sci. 2001 Apr 22;268(1469):847-54. doi: 10.1098/rspb.2000.1572.
Estimation of viral parameters, such as the basic reproductive number (R0) and infected cell life span, is central to the quantitative study of the within-host dynamics of viral diseases such as human immunodeficiency virus, hepatitis B or hepatitis C. As these parameters can rarely be determined directly, they are usually estimated indirectly by fitting mathematical models to viral load data. This paper investigates how parameter estimates obtained by such procedures depend on the assumptions made concerning the viral life cycle. It finds that estimates of the basic reproductive number obtained using viral load data collected during the initial stages of infection can depend quite sensitively on these assumptions. The use of models which neglect the intracellular delay before virion production can lead to severe underestimates of R0 and, hence, to overly optimistic predictions of how efficacious treatment must be in order to prevent or eradicate the disease. These results are also of importance for attempts at estimating R0 from similar epidemiological data as there is a correspondence between within-host and between-host models. Estimates of the life span of infected cells obtained from viral load data collected during drug treatment studies also depend on the assumptions made in modelling the virus life cycle. The use of more realistic descriptions of the life cycle is seen to increase estimates of infected cell life span, in addition to providing a new explanation for the shoulder phase seen during drug treatment. This study highlights the limitations of what can be learnt by fitting mathematical models to infectious disease data without detailed independent knowledge of the life cycle of the infectious agent.
对病毒参数的估计，如基本繁殖数（R0）和受感染细胞寿命，对于人类免疫缺陷病毒、乙型肝炎或丙型肝炎等病毒疾病在宿主内动态变化的定量研究至关重要。由于这些参数很少能直接确定，通常通过将数学模型拟合到病毒载量数据来间接估计。本文研究了通过此类程序获得的参数估计如何依赖于关于病毒生命周期的假设。研究发现，使用感染初期收集的病毒载量数据获得的基本繁殖数估计可能相当敏感地依赖于这些假设。使用忽略病毒粒子产生前细胞内延迟的模型可能会导致对R0的严重低估，从而对预防或根除疾病所需治疗的有效性做出过于乐观的预测。这些结果对于从类似流行病学数据估计R0的尝试也很重要，因为宿主内模型和宿主间模型存在对应关系。从药物治疗研究期间收集的病毒载量数据获得的受感染细胞寿命估计也依赖于病毒生命周期建模中所做的假设。除了为药物治疗期间出现的平台期提供新的解释外，使用更现实的生命周期描述还会增加对受感染细胞寿命的估计。这项研究突出了在没有关于传染因子生命周期的详细独立知识的情况下，通过将数学模型拟合到传染病数据所能了解到的内容的局限性。
