Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
Department of Molecular Virology and Microbiology, and Pediatrics, Baylor College of Medicine, Houston, Texas.
J Infect Dis. 2017 Dec 27;217(1):24-34. doi: 10.1093/infdis/jix543.
Data on how respiratory syncytial virus (RSV) genotypes influence disease severity and host immune responses is limited. Here, we characterized the genetic variability of RSV during 5 seasons, and evaluated the role of RSV subtypes, genotypes, and viral loads in disease severity and host transcriptional profiles.
A prospective, observational study was carried out, including a convenience sample of healthy infants hospitalized with RSV bronchiolitis. Nasopharyngeal samples for viral load quantitation, typing, and genotyping, and blood samples for transcriptome analyses were obtained within 24 hours of hospitalization. Multivariate models were constructed to identify virologic and clinical variables predictive of clinical outcomes.
We enrolled 253 infants (median age 2.1 [25%-75% interquartile range] months). RSV A infections predominated over RSV B and showed greater genotype variability. RSV A/GA2, A/GA5, and RSV B/BA were the most common genotypes identified. Compared to GA2 or BA, infants with GA5 infections had higher viral loads. GA5 infections were associated with longer hospital stay, and with less activation of interferon and increased overexpression of neutrophil genes.
RSV A infections were more frequent than RSV B, and displayed greater variability. GA5 infections were associated with enhanced disease severity and distinct host immune responses.
关于呼吸道合胞病毒(RSV)基因型如何影响疾病严重程度和宿主免疫反应的数据有限。在这里,我们描述了 5 个季节期间 RSV 的遗传变异性,并评估了 RSV 亚型、基因型和病毒载量在疾病严重程度和宿主转录谱中的作用。
进行了一项前瞻性观察研究,包括在 RSV 毛细支气管炎住院的健康婴儿的便利样本。在住院后 24 小时内获得鼻咽样本进行病毒载量定量、分型和基因分型,以及血液样本进行转录组分析。构建多变量模型以确定预测临床结果的病毒学和临床变量。
我们共纳入 253 名婴儿(中位数年龄 2.1 [25%-75%四分位间距] 个月)。RSV A 感染比 RSV B 更常见,且具有更大的基因型变异性。RSV A/GA2、A/GA5 和 RSV B/BA 是最常见的基因型。与 GA2 或 BA 相比,GA5 感染的婴儿病毒载量更高。GA5 感染与住院时间延长有关,与干扰素激活减少和中性粒细胞基因过度表达有关。
RSV A 感染比 RSV B 更常见,且具有更大的变异性。GA5 感染与疾病严重程度增加和宿主免疫反应明显不同有关。