Modelling original antigenic sin in dengue viral infection.

IF 0.8 4区 数学 Q4 BIOLOGY
Ryan Nikin-Beers, Stanca M Ciupe
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引用次数: 25

Abstract

Cross-reactive T cell responses induced by a primary dengue virus infection may contribute to increased disease severity following heterologous infections with a different virus serotype in a phenomenon known as the original antigenic sin. In this study, we developed and analyzed in-host models of T cell responses to primary and secondary dengue virus infections that considered the effect of T cell cross-reactivity in disease enhancement. We fitted the models to published patient data and showed that the overall infected cell killing is similar in dengue heterologous infections, resulting in dengue fever and dengue hemorrhagic fever. The contribution to overall killing, however, is dominated by non-specific T cell responses during the majority of secondary dengue hemorrhagic fever cases. By contrast, more than half of secondary dengue fever cases have predominant strain-specific T cell responses with high avidity. These results support the hypothesis that cross-reactive T cell responses occur mainly during severe disease cases of heterologous dengue virus infections.

模拟登革热病毒感染的原始抗原原罪。
可交叉反应的T细胞反应主要引起登革热病毒感染可能导致增加疾病严重程度不等的感染后病毒血清型不同的现象被称为原始抗原罪。在这项研究中,我们建立并分析了T细胞对原发性和继发性登革热病毒感染反应的宿主模型,该模型考虑了T细胞交叉反应在疾病增强中的作用。我们将模型与已发表的患者数据进行了拟合,结果表明,在导致登革热和登革出血热的登革热异源感染中,受感染细胞的总体杀伤是相似的。然而,在大多数继发性登革热出血热病例中,对总体杀伤的贡献主要是非特异性T细胞反应。相比之下,超过一半的继发性登革热病例具有高发生率的主要菌株特异性T细胞反应。这些结果支持交叉反应性T细胞反应主要发生在异源登革热病毒感染重症病例的假设。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.20
自引率
0.00%
发文量
15
审稿时长
>12 weeks
期刊介绍: Formerly the IMA Journal of Mathematics Applied in Medicine and Biology. Mathematical Medicine and Biology publishes original articles with a significant mathematical content addressing topics in medicine and biology. Papers exploiting modern developments in applied mathematics are particularly welcome. The biomedical relevance of mathematical models should be demonstrated clearly and validation by comparison against experiment is strongly encouraged. The journal welcomes contributions relevant to any area of the life sciences including: -biomechanics- biophysics- cell biology- developmental biology- ecology and the environment- epidemiology- immunology- infectious diseases- neuroscience- pharmacology- physiology- population biology
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