Prolonged persistence of measles virus RNA is characteristic of primary infection dynamics
Prolonged persistence of measles virus RNA is characteristic of primary infection dynamics
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DOI：
10.1073/pnas.1211138109
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发表时间：
2012-09-11
影响因子：
11.1
通讯作者：
Griffin, Diane E.
中科院分区：
文献类型：
--
作者：
Lin, Wen-Hsuan W.;Kouyos, Roger D.;Griffin, Diane E.
麻疹病毒（MeV）是急性感染后终身免疫的典范。然而，最近的研究表明，在感染后的一部分感染儿童中，MeV RNA在多个部位存在长达3个月。在这里，我们使用实验感染恒河猴，以表明，长期的RNA存在的特点是原发性感染。我们发现，病毒RNA在血液、呼吸道或淋巴结中的存留时间是感染性病毒的四到五倍，MeV RNA从血液中的清除分三个阶段进行：快速下降与感染性病毒的清除一致，反弹阶段增加到10倍，缓慢下降到无法检测的水平。为了进一步研究个体宿主免疫因素对MeV负载动力学的影响，我们开发了一个数学模型，该模型表达了MeV特异性T细胞应答、抗体应答、靶细胞限制和调节性T细胞的免疫抑制活性的强度方面的病毒复制和消除。基于该模型，我们证明了病毒动力学，虽然最初由T细胞调节，但需要抗体来消除病毒RNA。这些结果对我们对急性病毒感染、长期免疫力的发展以及潜在的病毒进化的看法具有深远的影响。
Measles virus (MeV) is the poster child for acute infection followed by lifelong immunity. However, recent work shows the presence of MeV RNA in multiple sites for up to 3 mo after infection in a proportion of infected children. Here, we use experimental infection of rhesus macaques to show that prolonged RNA presence is characteristic of primary infection. We found that viral RNA persisted in the blood, respiratory tract, or lymph nodes four to five times longer than the infectious virus and that the clearance of MeV RNA from blood happened in three phases: rapid decline coincident with clearance of infectious virus, a rebound phase with increases up to 10-fold, and a phase of slow decrease to undetectable levels. To examine the effect of individual host immune factors on MeV load dynamics further, we developed a mathematical model that expressed viral replication and elimination in terms of the strength of MeV-specific T-cell responses, antibody responses, target cell limitations, and immunosuppressive activity of regulatory T cells. Based on the model, we demonstrate that viral dynamics, although initially regulated by T cells, require antibody to eliminate viral RNA. These results have profound consequences for our view of acute viral infections, the development of prolonged immunity, and, potentially, viral evolution.