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在宿主中逃避交叉免疫和随机灭绝的突变病毒的出现的时间模式。

Temporal Pattern of the Emergence of a Mutant Virus Escaping Cross-Immunity and Stochastic Extinction Within a Host.

机构信息

Department of Biology, Faculty of Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.

出版信息

Bull Math Biol. 2023 Jul 28;85(9):81. doi: 10.1007/s11538-023-01184-x.

Abstract

A high mutation rate of the RNA virus results in the emergence of novel mutants that may escape the immunity activated by the original (wild-type) strain. However, many of them go extinct because of the stochasticity due to the small initial number of infected cells. In a previous paper, we studied the probability of escaping stochastic extinction when the novel mutant has a faster rate of infection and when it is resistant to a drug that suppresses the wild-type virus. In this study, we examine the effect of escaping the immune reaction of the host. Based on a continuous-time branching process with time-dependent rates, we conclude the chance for a mutant strain to be established [Formula: see text] decreases with time [Formula: see text] since the wild-type infection when the mutant is produced. The number of novel mutants that can escape extinction risk has a peak soon after the wild-type infection. The number of novel escape mutations produced per patient in the early phase of host infection is small both for very strong and very weak immune responses, and it attains its maximum value when immune activity is of an intermediate strength.

摘要

RNA 病毒的高突变率会导致新突变体的出现,这些突变体可能逃避由原始(野生型)菌株激活的免疫。然而,由于受感染细胞的初始数量较少,许多突变体由于随机性而灭绝。在之前的一篇论文中,我们研究了当新突变体具有更快的感染率并且对抑制野生型病毒的药物具有抗性时,逃避随机灭绝的概率。在这项研究中,我们检查了逃避宿主免疫反应的效果。基于具有时变率的连续时间分支过程,我们得出结论,当产生突变体时,突变株被建立的机会[公式:见文本]随着时间[公式:见文本]的推移而减少,当野生型感染时。在野生型感染后不久,能够逃避灭绝风险的新突变体数量就会达到峰值。在宿主感染的早期阶段,每个患者产生的新逃避突变的数量对于非常强和非常弱的免疫反应都很小,并且当免疫活性处于中等强度时达到最大值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766d/10382422/4df30a6d53c5/11538_2023_1184_Fig1_HTML.jpg

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