The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans.
The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans.
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DOI：
10.3390/v9110350
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发表时间：
2017-11-18
期刊：
影响因子：
--
通讯作者：
Perelson AS
中科院分区：
文献类型：
--
作者：
Goyal A;Ribeiro RM;Perelson AS
大约90-95%的B型肝炎病毒（HBV）感染的成年人不会进展到慢性期，而是自然恢复。溶细胞和非溶细胞免疫应答的强度是决定急性HBV感染命运的关键因素。此外，已经假设感染细胞的增殖导致未感染的后代和/或马槟榔碱介导的共价闭合环状DNA（cccDNA）的降解导致感染细胞的治愈是在人类急性HBV感染的清除中辅助适应性免疫应答的两种主要机制。我们采用拟合的数学模型，以人类急性感染数据与生理约束，以研究这些假设的机制在清除感染的作用。结果表明，在急性HBV感染的清除过程中，需要感染细胞的细胞增殖产生两个未感染的细胞，以最大限度地减少肝脏的破坏。相比之下，我们发现，单用马槟榔碱介导的感染细胞治愈不足以清除急性HBV感染。总之，我们的模型表明，HBV清除而没有致命的肝脏质量损失是与两个未感染的细胞后，受感染的细胞增殖的生产。
Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection data together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. In conclusion, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.
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影响因子：
13.5
作者：
Dahari, Harel;Shudo, Emi;Ribeiro, Ruy M.;Perelson, Alan S.
通讯作者：
Perelson, Alan S.
影响因子：
29.4
作者：
Dahari H;Layden-Almer JE;Kallwitz E;Ribeiro RM;Cotler SJ;Layden TJ;Perelson AS
通讯作者：
Perelson AS
影响因子：
4.4
作者：
Castro M;Lythe G;Molina-París C;Ribeiro RM
通讯作者：
Ribeiro RM
影响因子：
4.3
作者：
Ciupe SM;Ribeiro RM;Perelson AS
通讯作者：
Perelson AS
影响因子：
2
作者：
Ciupe, Stanca M.;Ribeiro, Ruy M.;Perelson, Alan S.
通讯作者：
Perelson, Alan S.