乙肝感染的早期事件：接种剂量的作用

StephenW

Early events in hepatitis B infection: the role of inoculum dose
Stanca M Ciupe  1 , Naveen K Vaidya  2   3   4 , Jonathan E Forde  5
Affiliations
Affiliations

    1
    Department of Mathematics, Virginia Tech, Blacksburg, 24060 VA, USA.
    2
    Department of Mathematics and Statistics, San Diego State University, San Diego, CA 92182, USA.
    3
    Computational Science Research Center, San Diego State University, San Diego, CA 92182, USA.
    4
    Viral Information Institute, San Diego State University, San Diego, CA 92182, USA.
    5
    Department of Mathematics and Computer Science, Hobart and William Smith Colleges, Geneva, New York 14456, USA.

    PMID: 33563115 DOI: 10.1098/rspb.2020.2715

Abstract

The relationship between the inoculum dose and the ability of the pathogen to invade the host is poorly understood. Experimental studies in non-human primates infected with different inoculum doses of hepatitis B virus have shown a non-monotonic relationship between dose magnitude and infection outcome, with high and low doses leading to 100% liver infection and intermediate doses leading to less than 0.1% liver infection, corresponding to CD4 T-cell priming. Since hepatitis B clearance is CD8 T-cell mediated, the question of whether the inoculum dose influences CD8 T-cell dynamics arises. To help answer this question, we developed a mathematical model of virus-host interaction following hepatitis B virus infection. Our model explains the experimental data well, and predicts that the inoculum dose affects both the timing of the CD8 T-cell expansion and the quality of its response, especially the non-cytotoxic function. We find that a low-dose challenge leads to slow CD8 T-cell expansion, weak non-cytotoxic functions, and virus persistence; high- and medium-dose challenges lead to fast CD8 T-cell expansion, strong cytotoxic and non-cytotoxic function, and virus clearance; while a super-low-dose challenge leads to delayed CD8 T-cell expansion, strong cytotoxic and non-cytotoxic function, and virus clearance. These results are useful for designing immune cell-based interventions.

Keywords: hepatitis B virus; inoculum dose; mathematical models.

StephenW

乙肝感染的早期事件：接种剂量的作用
Stanca M Ciupe 1，Naveen K Vaidya 2 3 4，Jonathan E Forde 5
隶属关系
隶属关系

    1个
    美国弗吉尼亚州布莱克斯堡，弗吉尼亚理工大学数学系，美国24060。
    2
    圣地亚哥州立大学数学与统计系，圣地亚哥，加利福尼亚州92182，美国。
    3
    圣地亚哥州立大学计算科学研究中心，圣地亚哥，加利福尼亚州92182，美国。
    4
    圣地亚哥州立大学病毒信息研究所，圣地亚哥，加利福尼亚州92182，美国。
    5
    霍巴特和威廉·史密斯学院数学与计算机科学系，美国纽约，日内瓦14456。

    PMID：33563115 DOI：10.1098 / rspb.2020.2715

抽象的

接种剂量和病原体入侵宿主的能力之间的关系知之甚少。对感染了不同接种剂量的乙型肝炎病毒的非人类灵长类动物的实验研究表明，剂量大小与感染结果之间存在非单调关系，高剂量和低剂量导致100％肝感染，中剂量导致小于0.1％肝脏感染，对应于CD4 T细胞启动。由于乙型肝炎清除是通过CD8 T细胞介导的，因此出现了接种剂量是否影响CD8 T细胞动力学的问题。为了帮助回答这个问题，我们建立了乙型肝炎病毒感染后病毒-宿主相互作用的数学模型。我们的模型很好地解释了实验数据，并预测接种剂量会影响CD8 T细胞扩增的时机及其反应质量，尤其是非细胞毒性功能。我们发现低剂量的攻击会导致CD8 T细胞扩增缓慢，无细胞毒性功能弱和病毒持续存在；高剂量和中等剂量的挑战导致CD8 T细胞快速扩增，强大的细胞毒性和非细胞毒性功能以及病毒清除能力；而超低剂量攻击会导致CD8 T细胞扩增延迟，强大的细胞毒性和非细胞毒性功能以及病毒清除。这些结果对于设计基于免疫细胞的干预措施很有用。

关键词：乙型肝炎病毒；接种剂量数学模型。

StephenW

https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2020.2715