Resnick Jessica D, Beer Michael A, Pekosz Andrew
W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
McKusick- Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
bioRxiv. 2023 Mar 9:2023.03.07.531609. doi: 10.1101/2023.03.07.531609.
Influenza A (IAV) and SARS-CoV-2 (SCV2) viruses represent an ongoing threat to public health. Both viruses target the respiratory tract, which consists of a gradient of cell types, receptor expression, and temperature. Environmental temperature has been an un-derstudied contributor to infection susceptibility and understanding its impact on host responses to infection could help uncover new insights into severe disease risk factors. As the nasal passageways are the initial site of respiratory virus infection, in this study we investigated the effect of temperature on host responses in human nasal epithelial cells (hNECs) utilizing IAV and SCV2 infection models. We demonstrate that temperature affects SCV2, but not IAV, viral replicative fitness and that SCV2 infected cultures are slower to mount an infection-induced response, likely due to suppression by the virus. Additionally, we show that that temperature not only changes the basal transcriptomic landscape of epithelial cells, but that it also impacts the response to infection. The induction of interferon and other innate immune responses were not drastically affected by temperature, suggesting that while the baseline antiviral response at different temperatures remains consistent, there may be metabolic or signaling changes that affect how well the cultures are able to adapt to new pressures such as infection. Finally, we show that hNECs respond differently to IAV and SCV2 infection in ways that give insight into how the virus is able to manipulate the cell to allow for replication and release. Taken together, these data give new insight into the innate immune response to respiratory infections and can assist in identifying new treatment strategies for respiratory infections.
甲型流感病毒（IAV）和严重急性呼吸综合征冠状病毒2（SCV2）对公众健康构成持续威胁。这两种病毒均侵袭呼吸道，呼吸道由多种不同类型的细胞、受体表达和温度梯度组成。环境温度对感染易感性的影响一直未得到充分研究，了解其对宿主感染反应的影响有助于揭示严重疾病风险因素的新见解。由于鼻腔通道是呼吸道病毒感染的初始部位，在本研究中，我们利用IAV和SCV2感染模型，研究了温度对人鼻上皮细胞（hNECs）中宿主反应的影响。我们证明，温度影响SCV2（而非IAV）的病毒复制适应性，并且SCV2感染的培养物引发感染诱导反应的速度较慢，这可能是由于病毒的抑制作用。此外，我们表明，温度不仅会改变上皮细胞的基础转录组格局，还会影响对感染的反应。干扰素和其他先天免疫反应的诱导并未受到温度的显著影响，这表明虽然不同温度下的基线抗病毒反应保持一致，但可能存在代谢或信号变化，影响培养物适应诸如感染等新压力的能力。最后，我们表明hNECs对IAV和SCV2感染的反应不同，这有助于深入了解病毒如何操纵细胞以实现复制和释放。综上所述，这些数据为呼吸道感染的先天免疫反应提供了新的见解，并有助于确定呼吸道感染的新治疗策略。
