Koizumi Yoshiki, Bonsall Michael B
Department of Biology, University of Oxford, South Parks Road, Oxford OX1 3RB, United Kingdom.
AIDS Clinical Center, National Center for Global Health and Medicine, Japan Institute for Health Security, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Virus Evol. 2025 Jun 6;11(1):veaf043. doi: 10.1093/ve/veaf043. eCollection 2025.
Cancer-inducing viruses (oncogenic viruses) are linked to over 10% of cancer cases. Although the molecular details of viral oncogenesis are well-documented, the evolutionary mechanisms by which viruses have acquired oncogenic properties remain poorly understood. Here, we investigate the evolutionary conditions affecting viral oncogenicity across both within- and between-host scales using mathematical models of oncovirus-immune system interactions, conceptualized as an extended shared enemy-victim relationship. We begin by examining how oncogenic traits impact within-host viral dynamics, focusing on the transformation rate of infected cells into pre-cancerous states and the pre-cancerous cell proliferation rate. In various scenarios reflecting different within-host conditions, we then identify the transformation and proliferation rates that maximize within- and between-host viral fitness. We find that the transformation rate maximizing the viral load depends on the viral production rate, immunogenicity, and the immune-mediated elimination rate of pre-cancerous cells. We also identify conditions under which an intermediate proliferation rate minimizes within- and between-host viral fitness: in that scenario, a lower or higher proliferation rate leads to a higher viral load, providing a possible explanation for the diversity of oncogenic viruses. The analyses presented here provide insights into the evolutionary drivers affecting viral oncogenicity and highlight the complexity of oncogenic virus-immune system interactions.
致癌病毒（致癌性病毒）与超过10%的癌症病例相关。尽管病毒致癌作用的分子细节已有充分记录，但病毒获得致癌特性的进化机制仍知之甚少。在此，我们使用肿瘤病毒-免疫系统相互作用的数学模型，从宿主内和宿主间尺度研究影响病毒致癌性的进化条件，将其概念化为一种扩展的共同敌害-受害者关系。我们首先研究致癌特性如何影响宿主内病毒动态，重点关注感染细胞向癌前状态的转化率和癌前细胞增殖率。在反映不同宿主内条件的各种情况下，我们随后确定使宿主内和宿主间病毒适应性最大化的转化率和增殖率。我们发现，使病毒载量最大化的转化率取决于病毒产生率、免疫原性以及癌前细胞的免疫介导清除率。我们还确定了中间增殖率使宿主内和宿主间病毒适应性最小化的条件：在该情况下，较低或较高的增殖率会导致更高的病毒载量，这为致癌病毒的多样性提供了一种可能的解释。本文所呈现的分析为影响病毒致癌性的进化驱动因素提供了见解，并突出了致癌病毒-免疫系统相互作用的复杂性。
