Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study.
Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study.
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DOI：
10.1016/s2666-5247(20)30114-2
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Foxman EF
中科院分区：
文献类型：
--
作者：
Wu A;Mihaylova VT;Landry ML;Foxman EF
在2009年新出现的甲型流感病毒(IAV；H1N1pdm09)大流行期间，来自几个欧洲国家的数据表明，该病毒的传播可能因每年的秋季鼻病毒流行而中断。我们的目的是利用临床数据和一个实验模型来研究鼻病毒和IAV之间的病毒干扰。我们进行了临床数据分析和实验性感染研究，调查了连续三个冬季(11月1日至3月1日，2016-17日，2017-18年，2018-19年)在耶鲁-纽黑文医院(CT)多重聚合酶链式反应(≥)检测的成人(21岁)呼吸道标本中鼻病毒和流行性感冒病毒的共存情况。我们使用从EPIC系统电子病历系统提取的数据，比较了观察到的和预期的共同检测。为了评估鼻病毒感染如何影响随后的IAV感染，我们将鼻病毒(HRV-01a；感染的多样性[MOI]0·1)接种于分化的原代人呼吸道上皮细胞培养物中，或进行模拟感染。感染后第3天，接种相同的IAV(H1N1绿色荧光蛋白[GFP]报告病毒或H1N1pdm09；MOI0.1)。我们在鼻病毒或模拟感染后第3天使用逆转录定量聚合酶链式反应或显微镜定量宿主细胞中干扰素刺激基因(ISGs)的mRNAs，在鼻病毒或模拟感染后第4、5或6天使用IAV RNA进行定量。我们还在BX795(6μM)存在的情况下进行了序贯感染研究，以抑制干扰素反应。我们比较了ISG和IAV RNA的表达以及IAV报告病毒对GFP的表达。在2016年7月1日至2019年6月30日期间，对8284份鼻病毒(n=3821)或IAV(n=4463)任何检测方法阳性的呼吸道样本进行了检测，以确定11月1日至3月1日为病毒共循环的高峰期。在对符合纳入标准的样本进行筛选后(n=13707)，共检测到989例(7.2%)鼻病毒和922例(6.7%)IAV，共同检测的几率明显低于预期(优势比0·16，95%可信区间0·09-0·28)。鼻病毒感染细胞后诱导ISG表达并在3天后对IAV感染具有保护作用，导致IAV H1N1pdm09病毒RNA在鼻病毒接种后第5天下降约5万倍。阻断干扰素反应恢复了鼻病毒感染后IAV的复制。这些发现表明，一种呼吸道病毒可以通过刺激呼吸道粘膜中的抗病毒防御来阻止另一种呼吸道病毒的感染，这支持了鼻病毒的干扰扰乱了2009年欧洲IAV大流行的观点。这些结果表明，病毒干扰可能会影响流行病的进程，在设计针对季节性流感疫情和正在进行的新冠肺炎大流行的干预措施时，应考虑这种可能性。国立卫生研究院、国家普通医学科学研究所和耶鲁大学检验医学系。
During the 2009 pandemic of an emerging influenza A virus (IAV; H1N1pdm09), data from several European countries indicated that the spread of the virus might have been interrupted by the annual autumn rhinovirus epidemic. We aimed to investigate viral interference between rhinovirus and IAV with use of clinical data and an experimental model. We did a clinical data analysis and experimental infection study to investigate the co-occurrence of rhinovirus and IAV in respiratory specimens from adults (≥21 years) tested with a multiplex PCR panel at Yale-New Haven Hospital (CT, USA) over three consecutive winter seasons (Nov 1 to March 1, 2016–17, 2017–18, and 2018–19). We compared observed versus expected co-detections using data extracted from the Epic Systems electronic medical record system. To assess how rhinovirus infection affects subsequent IAV infection, we inoculated differentiated primary human airway epithelial cultures with rhinovirus (HRV-01A; multiplicity of infection [MOI] 0·1) or did mock infection. On day 3 post-infection, we inoculated the same cultures with IAV (H1N1 green fluorescent protein [GFP] reporter virus or H1N1pdm09; MOI 0·1). We used reverse transcription quantitative PCR or microscopy to quantify host cell mRNAs for interferon-stimulated genes (ISGs) on day 3 after rhinovirus or mock infection and IAV RNA on days 4, 5, or 6 after rhinovirus or mock infection. We also did sequential infection studies in the presence of BX795 (6 μM), to inhibit the interferon response. We compared ISG expression and IAV RNA and expression of GFP by IAV reporter virus. Between July 1, 2016, and June 30, 2019, examination of 8284 respiratory samples positive for either rhinovirus (n=3821) or IAV (n=4463) by any test method was used to establish Nov 1 to March 1 as the period of peak virus co-circulation. After filtering for samples within this time frame meeting the inclusion criteria (n=13 707), there were 989 (7·2%) rhinovirus and 922 (6·7%) IAV detections, with a significantly lower than expected odds of co-detection (odds ratio 0·16, 95% CI 0·09–0·28). Rhinovirus infection of cell cultures induced ISG expression and protected against IAV infection 3 days later, resulting in an approximate 50 000-fold decrease in IAV H1N1pdm09 viral RNA on day 5 post-rhinovirus inoculation. Blocking the interferon response restored IAV replication following rhinovirus infection. These findings show that one respiratory virus can block infection with another through stimulation of antiviral defences in the airway mucosa, supporting the idea that interference from rhinovirus disrupted the 2009 IAV pandemic in Europe. These results indicate that viral interference can potentially affect the course of an epidemic, and this possibility should be considered when designing interventions for seasonal influenza epidemics and the ongoing COVID-19 pandemic. National Institutes of Health, National Institute of General Medical Sciences, and the Yale Department of Laboratory Medicine.
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DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/j.jcv.2009.03.008
发表时间：
2009-05
期刊：
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
影响因子：
--
作者：
Greer RM;McErlean P;Arden KE;Faux CE;Nitsche A;Lambert SB;Nissen MD;Sloots TP;Mackay IM
通讯作者：
Mackay IM
影响因子：
4.7
作者：
Anestad, Gabriel;Nordbo, Svein Arne
通讯作者：
Nordbo, Svein Arne
影响因子：
6.4
作者：
Yu, Jinsheng;Peterson, Derick R.;Storch, Gregory A.
通讯作者：
Storch, Gregory A.
影响因子：
4.8
作者：
Clark, Kristopher;Plater, Lorna;Cohen, Philip
通讯作者：
Cohen, Philip