Nakano Satoko, Hamele Cait E, Tata Aleksandra, Tata Purushothama Rao, Heaton Nicholas S
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.
Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina, USA.
mBio. 2025 Feb 5;16(2):e0274324. doi: 10.1128/mbio.02743-24. Epub 2024 Dec 31.
Respiratory epithelial cells can survive direct infection by influenza viruses, and the long-term consequences of that infection have been characterized in a subset of proximal airway cell types. The impact on the cells that survive viral infection in the distal lung epithelia, however, is much less well-characterized. Utilizing a Cre-expressing influenza B virus (IBV) and a lox-stop-lox tdTomato reporter mouse model, we identified that alveolar type 2 (AT2) pneumocytes, a progenitor cell type in the distal lung, can survive viral infection. We show that survival of infection is associated with transcriptional dysregulation compared to bystander AT2 pneumocytes from the same lung. Furthermore, experiments revealed a significant reduction in proliferation rates in survivor AT2 pneumocytes compared to matched, non-directly infected bystander cells. Our findings not only enhance our understanding of the AT2 pneumocyte response to IBV infection but could also have broader implications for the mechanisms of respiratory epithelial repair post-viral infection.
Alveolar type 2 (AT2) pneumocytes are a cell type critical for repair of the distal lung after an injury, such as a viral infection. After epithelial damage, AT2 pneumocytes proliferate for both self-renewal and differentiation into type I pneumocytes to repopulate the epithelium. Theoretically, some of the long-term lung sequelae associated with viral infections could be the result of inappropriate AT2 behavior. Here, the authors report that during an influenza B virus infection, some of the actively infected AT2 pneumocytes can ultimately eliminate all traces of the viral RNA and persist in the host long term. As a consequence of having been infected, however, the cells display an altered transcriptional profile and decreased proliferative capacity. These data together suggest a mechanism for how an acute viral infection can have long-term impacts on the pulmonary system.
呼吸道上皮细胞能够在流感病毒的直接感染下存活，并且这种感染的长期后果已在一部分近端气道细胞类型中得到了描述。然而，对于远端肺上皮中在病毒感染后存活的细胞所产生的影响，目前了解得还很少。利用一种表达Cre的乙型流感病毒（IBV）和一种lox-stop-lox tdTomato报告基因小鼠模型，我们确定了肺泡II型（AT2）肺细胞，即远端肺中的一种祖细胞类型，能够在病毒感染后存活。我们发现，与来自同一肺的旁观者AT2肺细胞相比，感染后的存活与转录失调有关。此外，实验表明，与匹配的、未直接感染的旁观者细胞相比，存活的AT2肺细胞的增殖率显著降低。我们的研究结果不仅增进了我们对AT2肺细胞对IBV感染反应的理解，还可能对病毒感染后呼吸道上皮修复的机制产生更广泛的影响。
肺泡II型（AT2）肺细胞是损伤（如病毒感染）后远端肺修复的关键细胞类型。上皮损伤后，AT2肺细胞会增殖以实现自我更新并分化为I型肺细胞，从而重新填充上皮。理论上，一些与病毒感染相关的长期肺部后遗症可能是AT2细胞行为不当的结果。在此，作者报告称，在乙型流感病毒感染期间，一些被积极感染的AT2肺细胞最终能够消除所有病毒RNA痕迹并长期在宿主体内持续存在。然而，由于曾经被感染，这些细胞表现出转录谱改变和增殖能力下降。这些数据共同提示了一种急性病毒感染如何对肺部系统产生长期影响的机制。
