Gilbert-Girard Shella, Piret Jocelyne, Rhéaume Chantal, Carbonneau Julie, Goyette Nathalie, Couture Christian, Boivin Guy
Research Center of the CHU of Quebec-Laval University, Quebec City, Quebec, Canada.
Department of Pathology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, Québec, Canada.
Microbiol Spectr. 2025 Jun 3;13(6):e0318724. doi: 10.1128/spectrum.03187-24. Epub 2025 May 14.
Epidemiological studies suggest that respiratory syncytial virus (RSV) and influenza A virus (IAV) might interfere with each other. Viral interference mainly relies on interferon production elicited by a first virus that reduces the replication of a second virus. In this paper, we first investigated the interactions between RSV-A2 and influenza A(H1N1)pdm09 in BALB/c mice infected with each single virus or both viruses simultaneously or sequentially before, at the peak of interferon elicited by each virus, or after that peak. IAV reduced by almost 3.0 logs the replication of RSV administered at the peak of interferon induced by influenza, but the opposite was not true. However, IAV-infected mice challenged with RSV or the vehicle lost more weight and had a lower survival rate compared to single infections. Interferon expression, cytokine levels, and pulmonary inflammation were almost similar between groups. Disease worsening was attributed to an aggravation of IAV-induced pulmonary congestion following intranasal instillation of fluid (with or without RSV). In human airway epithelia, IAV also interfered with RSV replication. Viral interference was dependent on the timing and sequence of infections but not on differential interferon susceptibilities. Overall, our results help to understand the mechanisms of the interaction between two major respiratory viruses.IMPORTANCERespiratory syncytial and influenza viruses may interfere with each other based on epidemiological studies. It is suggested that a first virus may induce the production of interferon and interfere with the replication of a second unrelated virus. Our data showed that the influenza A virus interferes with respiratory syncytial virus replication in mouse lungs, but the opposite was not observed. In reconstituted human airway epithelia, viral interference was dependent on the timing and sequence of infections but not on differential interferon susceptibilities. Understanding the mechanisms of interaction between respiratory viruses may help the development of prophylactic or therapeutic modalities.
流行病学研究表明，呼吸道合胞病毒（RSV）和甲型流感病毒（IAV）可能会相互干扰。病毒干扰主要依赖于第一种病毒引发的干扰素产生，这种干扰素会减少第二种病毒的复制。在本文中，我们首先研究了RSV-A2与甲型H1N1流感病毒（A(H1N1)pdm09）在BALB/c小鼠中的相互作用，这些小鼠分别感染单一病毒、同时感染两种病毒或在每种病毒诱导的干扰素峰值之前、峰值时或峰值之后依次感染两种病毒。甲型流感病毒在流感诱导的干扰素峰值时给药，可使呼吸道合胞病毒的复制减少近3.0个对数，但反之则不成立。然而，与单一感染相比，感染甲型流感病毒后再用呼吸道合胞病毒或载体攻击的小鼠体重减轻更多，存活率更低。各组之间的干扰素表达、细胞因子水平和肺部炎症几乎相似。疾病恶化归因于鼻内滴注液体（有或没有呼吸道合胞病毒）后甲型流感病毒诱导的肺充血加重。在人气道上皮细胞中，甲型流感病毒也会干扰呼吸道合胞病毒的复制。病毒干扰取决于感染的时间和顺序，而不取决于干扰素敏感性的差异。总体而言，我们的结果有助于理解两种主要呼吸道病毒之间相互作用的机制。
重要性
根据流行病学研究，呼吸道合胞病毒和流感病毒可能会相互干扰。有人提出，第一种病毒可能会诱导干扰素的产生，并干扰第二种无关病毒的复制。我们的数据表明，甲型流感病毒会干扰小鼠肺部呼吸道合胞病毒的复制，但未观察到相反的情况。在重组的人气道上皮细胞中，病毒干扰取决于感染的时间和顺序，而不取决于干扰素敏感性的差异。了解呼吸道病毒之间的相互作用机制可能有助于开发预防或治疗方法。
