期刊
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
卷 288, 期 1944, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rspb.2020.2715
关键词
hepatitis B virus; mathematical models; inoculum dose
资金
- National Science Foundation [1813011]
- UGP award from SDSU
- Direct For Mathematical & Physical Scien
- Division Of Mathematical Sciences [1813011] Funding Source: National Science Foundation
Experimental studies have shown a non-monotonic relationship between the inoculum dose of hepatitis B virus and infection outcome, with different doses leading to different CD8 T-cell dynamics and infection outcomes. The mathematical model developed in this study explains and predicts how the inoculum dose affects the timing and quality of CD8 T-cell response, providing insights for the design of immune cell-based interventions.
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.
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