Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India.
Central Forensic Science Laboratory, Pune, DFSS, Ministry of Home Affairs, Govt. of India, Talegaon MIDC Phase-1, Near JCB Factory, Pune, Maharashtra, 410506, India.
Folia Microbiol (Praha). 2024 Feb;69(1):41-57. doi: 10.1007/s12223-023-01091-7. Epub 2023 Sep 6.
The asymmetrical distribution of the cellular organelles inside the cell is maintained by a group of cell polarity proteins. The maintenance of polarity is one of the vital host defense mechanisms against pathogens, and the loss of it contributes to infection facilitation and cancer progression. Studies have suggested that infection of viruses and bacteria alters cell polarity. Helicobacter pylori and Epstein-Barr virus are group I carcinogens involved in the progression of multiple clinical conditions besides gastric cancer (GC) and Burkitt's lymphoma, respectively. Moreover, the coinfection of both these pathogens contributes to a highly aggressive form of GC. H. pylori and EBV target the host cell polarity complexes for their pathogenesis. H. pylori-associated proteins like CagA, VacA OipA, and urease were shown to imbalance the cellular homeostasis by altering the cell polarity. Similarly, EBV-associated genes LMP1, LMP2A, LMP2B, EBNA3C, and EBNA1 also contribute to altered cell asymmetry. This review summarized all the possible mechanisms involved in cell polarity deformation in H. pylori and EBV-infected epithelial cells. We have also discussed deregulated molecular pathways like NF-κB, TGF-β/SMAD, and β-catenin in H. pylori, EBV, and their coinfection that further modulate PAR, SCRIB, or CRB polarity complexes in epithelial cells.
细胞内细胞器官的不对称分布由一组细胞极性蛋白维持。极性的维持是宿主对抗病原体的重要防御机制之一，而其丧失则有助于感染的促进和癌症的进展。研究表明，病毒和细菌的感染会改变细胞极性。幽门螺杆菌和 Epstein-Barr 病毒分别是导致多种临床疾病（除胃癌 [GC] 和伯基特淋巴瘤外）进展的 I 组致癌物。此外，这两种病原体的共同感染导致 GC 的高度侵袭性形式。H. pylori 和 EBV 针对宿主细胞极性复合物进行发病。已显示 H. pylori 相关蛋白如 CagA、VacA OipA 和脲酶通过改变细胞极性来破坏细胞内稳态。类似地，EBV 相关基因 LMP1、LMP2A、LMP2B、EBNA3C 和 EBNA1 也有助于细胞不对称性的改变。本综述总结了 H. pylori 和 EBV 感染的上皮细胞中细胞极性变形涉及的所有可能机制。我们还讨论了 H. pylori、EBV 及其共同感染中失调的分子途径，如 NF-κB、TGF-β/SMAD 和 β-连环蛋白，它们进一步调节上皮细胞中的 PAR、SCRIB 或 CRB 极性复合物。
