Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Hospital Universitário da Universidade de São Paulo, São Paulo, SP, Brazil.
PLoS One. 2019 Mar 7;14(3):e0213501. doi: 10.1371/journal.pone.0213501. eCollection 2019.
Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, when infections by other viruses, such as rhinovirus, also occur and are clinically indistinguishable from those caused by HRSV. In hospitalized infants with bronchiolitis, the analysis of gene expression profiles from peripheral blood mononuclear cells (PBMC) may be useful for the rapid identification of etiological factors, as well as for developing diagnostic tests, and elucidating pathogenic mechanisms triggered by different viral agents. In this study we conducted a comparative global gene expression analysis of PBMC obtained from two groups of infants with acute viral bronchiolitis who were infected by HRSV (HRSV group) or by HRV (HRV group). We employed a weighted gene co-expression network analysis (WGCNA) which allows the identification of transcriptional modules and their correlations with HRSV or HRV groups. This approach permitted the identification of distinct transcription modules for the HRSV and HRV groups. According to these data, the immune response to HRSV infection-comparatively to HRV infection-was more associated to the activation of the interferon gamma signaling pathways and less related to neutrophil activation mechanisms. Moreover, we also identified host-response molecular markers that could be used for etiopathogenic diagnosis. These results may contribute to the development of new tests for respiratory virus identification. The finding that distinct transcriptional profiles are associated to specific host responses to HRSV or to HRV may also contribute to the elucidation of the pathogenic mechanisms triggered by different respiratory viruses, paving the way for new therapeutic strategies.
人类呼吸道合胞病毒(HRSV)是婴儿期第一年毛细支气管炎的主要病因,此时也会发生其他病毒(如鼻病毒)感染,且临床症状与 HRSV 感染无法区分。在患有毛细支气管炎的住院婴儿中,外周血单个核细胞(PBMC)的基因表达谱分析可能有助于快速识别病因,以及开发诊断测试和阐明不同病毒引发的发病机制。在这项研究中,我们对两组急性病毒性毛细支气管炎婴儿的 PBMC 进行了比较全基因组表达分析,这些婴儿分别感染了 HRSV(HRSV 组)或 HRV(HRV 组)。我们采用了加权基因共表达网络分析(WGCNA),该方法可以识别转录模块及其与 HRSV 或 HRV 组的相关性。这种方法允许为 HRSV 和 HRV 组分别鉴定出独特的转录模块。根据这些数据,与 HRV 感染相比,HRSV 感染引起的免疫反应与干扰素 γ信号通路的激活更为相关,而与中性粒细胞激活机制的相关性较小。此外,我们还鉴定了宿主反应分子标志物,可用于病因学诊断。这些结果可能有助于开发新的呼吸病毒鉴定测试。特定的宿主对 HRSV 或 HRV 的反应与特定的转录谱相关的发现,也可能有助于阐明不同呼吸道病毒引发的发病机制,为新的治疗策略铺平道路。