Goncheva Mariya I, Gibson Richard M, Shouldice Ainslie C, Dikeakos Jimmy D, Heinrichs David E
Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5C1, Canada.
ImPaKT Laboratory, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.
iScience. 2023 Feb 17;26(2):105975. doi: 10.1016/j.isci.2023.105975. Epub 2023 Jan 13.
The Severe Acute Respiratory Syndrome Coronavirus 2 (CoV-2) pandemic has affected millions globally. A significant complication of CoV-2 infection is secondary bacterial co-infection, as seen in approximately 25% of severe cases. The most common organism isolated during co-infection is Here, we describe the development of an co-infection model where both viral and bacterial replication kinetics may be examined. We demonstrate CoV-2 infection does not alter bacterial interactions with host epithelial cells. In contrast, enhances CoV-2 replication by 10- to 15-fold. We identify this pro-viral activity is due to the iron-regulated surface determinant A (IsdA) protein and demonstrate IsdA modifies host transcription. We find that IsdA alters Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) signaling, by affecting JAK2-STAT3 levels, ultimately leading to increased viral replication. These findings provide key insight into the molecular interactions between host cells, CoV-2 and during co-infection.
严重急性呼吸综合征冠状病毒2（CoV-2）大流行已在全球范围内影响了数百万人。CoV-2感染的一个重要并发症是继发性细菌共感染，在约25%的重症病例中可见。共感染期间分离出的最常见病原体是……在此，我们描述了一种共感染模型的构建，在该模型中可以检测病毒和细菌的复制动力学。我们证明CoV-2感染不会改变细菌与宿主上皮细胞的相互作用。相反，……可使CoV-2复制增强10至15倍。我们确定这种促进病毒的活性归因于……铁调节表面决定簇A（IsdA）蛋白，并证明IsdA可改变宿主转录。我们发现IsdA通过影响JAK2-STAT3水平改变Janus激酶-信号转导子和转录激活子（JAK-STAT）信号传导，最终导致病毒复制增加。这些发现为共感染期间宿主细胞、CoV-2和……之间的分子相互作用提供了关键见解。
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