Lau Jessica W, Kim Young-In, Murphy Ryan, Newman Ruchi, Yang Xiao, Zody Michael, DeVincenzo John, Grad Yonatan H
Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA 02115, United States.
Department of Pediatrics, University of Tennessee School of Medicine, Memphis, TN 38103, United States; Children's Foundation Research Institute at LeBonheur Children's Hospital, Memphis, TN 38103, United States.
Virology. 2017 Oct;510:289-296. doi: 10.1016/j.virol.2017.07.017. Epub 2017 Aug 3.
As RNA virus mutation occurs during replication within host cells, we hypothesized that viral evolution during acute infections in healthy hosts reflects host immune pressure. We therefore investigated the within-host diversification of human respiratory syncytial virus (RSV), a highly prevalent cause of acute respiratory infections. We evaluated healthy adults experimentally infected with an identical inoculum and infants hospitalized with naturally acquired infections. In aggregate, viral diversification in adults peaked at day 3, with overrepresentation of diversity in the matrix protein 2 (M2) and non-structural protein 2 (NS2) genes. In one subject, delayed viral clearance was accompanied by a late peak of diversity at day 10 in known and predicted B and T cell epitopes. In contrast, infant infections showed much less viral diversity. Our findings suggest multiple overlapping mechanisms for early control of acute viral infections, which may differ between age groups and host immune responses.
由于RNA病毒在宿主细胞内复制过程中会发生突变，我们推测健康宿主急性感染期间的病毒进化反映了宿主免疫压力。因此，我们研究了人类呼吸道合胞病毒（RSV）在宿主体内的多样性，RSV是急性呼吸道感染的一种高度常见病因。我们评估了实验性感染相同接种物的健康成年人以及因自然感染而住院的婴儿。总体而言，成年人的病毒多样性在第3天达到峰值，基质蛋白2（M2）和非结构蛋白2（NS2）基因的多样性占比过高。在一名受试者中，病毒清除延迟伴随着已知和预测的B细胞和T细胞表位在第10天出现多样性的晚期峰值。相比之下，婴儿感染显示出的病毒多样性要少得多。我们的研究结果表明，急性病毒感染早期控制存在多种重叠机制，这些机制可能因年龄组和宿主免疫反应而异。
