Murray John M, Wieland Stefan F, Purcell Robert H, Chisari Francis V
School of Mathematics, University of New South Wales, Sydney NSW 2052, Australia.
Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17780-5. doi: 10.1073/pnas.0508913102. Epub 2005 Nov 23.
Mathematical modeling was performed to test the extent to which cytopathic and noncytopathic T cell effector functions contribute to resolution of hepatitis B virus (HBV) infection in three acutely infected chimpanzees. Simulations based exclusively on cytopathic functions show a poor fit to the data and would require the destruction and regeneration of approximately 11 livers for clearance to occur. In contrast, a simulation based on a combination of cytopathic and noncytopathic functions provided a significantly better fit to the data (P < 0.001) and required as much as 5-fold less destruction to clear the virus from the liver. The best fit simulation supports the notion that during the early phase of HBV clearance, noncytopathic T cell effector mechanisms inhibit viral replication and greatly shorten the half-life of the long lived covalently closed circular viral DNA transcriptional template, thereby limiting the extent to which cytopathic T cell effector functions and tissue destruction are required to terminate acute HBV infection.
进行数学建模以测试细胞病变和非细胞病变的T细胞效应功能在多大程度上有助于三只急性感染黑猩猩的乙型肝炎病毒（HBV）感染的清除。仅基于细胞病变功能的模拟与数据拟合不佳，并且需要破坏和再生大约11个肝脏才能实现清除。相比之下，基于细胞病变和非细胞病变功能组合的模拟与数据的拟合度明显更好（P < 0.001），并且清除肝脏中的病毒所需的破坏减少多达5倍。最佳拟合模拟支持这样的观点，即在HBV清除的早期阶段，非细胞病变的T细胞效应机制抑制病毒复制并大大缩短长寿共价闭合环状病毒DNA转录模板的半衰期，从而限制了终止急性HBV感染所需的细胞病变T细胞效应功能和组织破坏的程度。
