造型细胞到细胞传播乙型肝炎病毒的影响

StephenW

PLoS One. 2016 Aug 25;11(8):e0161978. doi: 10.1371/journal.pone.0161978.
Modelling the Impact of Cell-To-Cell Transmission in Hepatitis B Virus.Goyal A1, Murray JM1.
Author information

• 1School of Mathematics and Statistics, UNSW, Sydney, NSW, Australia.
  

AbstractCell-free virus is a well-recognized and efficient mechanism for the spread of hepatitis B virus (HBV) infection in the liver. Cell-to-cell transmission (CCT) can be a more efficient means of virus propagation. Despite experimental evidence implying CCT occurs in HBV, its relative impact is uncertain. We develop a 3-D agent-based model where each hepatocyte changes its viral state according to a dynamical process driven by cell-free virus infection, CCT and intracellular replication. We determine the relative importance of CCT in the development and resolution of acute HBV infection in the presence of cytolytic (CTL) and non-CTL mechanisms. T cell clearance number is defined as the minimum number of infected cells needed to be killed by each T cell at peak infection that results in infection clearance within 12 weeks with hepatocyte turnover (HT, number of equivalent livers) ≤3. We find that CCT has very little impact on the establishment of infection as the mean cccDNA copies/cell remains between 15 to 20 at the peak of the infection regardless of CCT strength. In contrast, CCT inhibit immune-mediated clearance of acute HBV infection as higher CCT strength requires higher T cell clearance number and increases the probability of T cell exhaustion. An effective non-CTL inhibition can counter these negative effects of higher strengths of CCT by supporting rapid, efficient viral clearance and with little liver destruction. This is evident as the T cell clearance number drops by approximately 50% when non-CTL inhibition is increased from 10% to 80%. Higher CCT strength also increases the probability of the incidence of fulminant hepatitis with this phenomenon being unlikely to arise for no CCT. In conclusion, we report the possibility of CCT impacting HBV clearance and its contribution to fulminant hepatitis.


PMID:27560827DOI:10.1371/journal.pone.0161978

StephenW

公共科学图书馆之一。 2016年8月25日; 11（8）：e0161978。 DOI：10.1371 / journal.pone.0161978。
造型细胞到细胞传播乙型肝炎病毒的影响。
戈亚尔A1，穆雷JM1。
作者信息

    数学与统计，新南威尔士大学，悉尼，新南威尔士，澳大利亚1School。

抽象

无细胞病毒为乙型肝炎病毒（HBV）感染的肝脏中传播的一个公认的和有效的机制。细胞至细胞传播（CCT）可病毒传播的更有效的手段。尽管实验证据暗示CCT乙肝病毒时，其相对影响是不确定的。我们开发了一个3-D基于代理的模型，其中每个肝细胞根据无细胞病毒感染，CCT和细胞内复制驱动的动力过程改变其病毒状态。我们确定在细胞溶解（CTL）和非CTL机制的存在下发展CCT和急性HBV感染的分辨率的相对重要性。 T细胞间隙数被定义为需要通过在峰值感染与肝细胞周转（HT，等效肝脏的数目）≤3导致感染的间隙在12周内每T细胞被杀死被感染的细胞的最小数目。我们发现CCT对建立感染的影响非常小为平均值的cccDNA拷贝/细胞在感染的高峰不管CCT强度保持在15至20个。与此相反，CCT抑制急性HBV感染的免疫介导的清除率作为更高的CCT强度需要更高的T细胞的间隙数目并增加了T细胞耗竭的概率。一个有效的非CTL抑制可以通过支持快速，有效的病毒清除和肝脏少破坏对抗CCT高强度的这些负面影响。作为T细胞间隙数约50％下降时非CTL抑制从10％提高到80％，这是显而易见的。更高的CCT强度也与这种现象是不大可能出现无CCT增加暴发性肝炎的发生的概率。总之，我们报告CCT的影响病毒清除及其对暴发性肝炎贡献的可能性。

结论：
    27560827
DOI：
    10.1371 / journal.pone.0161978