Hare David, Collins Susan, Cuddington Breanne, Mossman Karen
Pathology and Molecular Medicine, McMaster University, 1280 Main Str. West, Hamilton, ON L8S 4L8, Canada.
Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Str. West, Hamilton, ON L8S 4L8, Canada.
Viruses. 2016 Nov 1;8(11):297. doi: 10.3390/v8110297.
Viruses interact intimately with the host cell at nearly every stage of replication, and the cell model that is chosen to study virus infection is critically important. Although primary cells reflect the phenotype of healthy cells in vivo better than cell lines, their limited lifespan makes experimental manipulation challenging. However, many tumor-derived and artificially immortalized cell lines have defects in induction of interferon-stimulated genes and other antiviral defenses. These defects can affect virus replication, especially when cells are infected at lower, more physiologically relevant, multiplicities of infection. Understanding the selective pressures and mechanisms underlying the loss of innate signaling pathways is helpful to choose immortalized cell lines without impaired antiviral defense. We describe the trials and tribulations we encountered while searching for an immortalized cell line with intact innate signaling, and how directed immortalization of primary cells avoids many of the pitfalls of spontaneous immortalization.
病毒在复制的几乎每个阶段都与宿主细胞密切相互作用，因此选择用于研究病毒感染的细胞模型至关重要。虽然原代细胞比细胞系能更好地反映体内健康细胞的表型，但其有限的寿命使得实验操作具有挑战性。然而，许多肿瘤衍生的和人工永生化的细胞系在诱导干扰素刺激基因和其他抗病毒防御方面存在缺陷。这些缺陷会影响病毒复制，尤其是当细胞以较低的、更符合生理相关的感染复数被感染时。了解先天信号通路丧失背后的选择压力和机制有助于选择抗病毒防御未受损的永生化细胞系。我们描述了在寻找具有完整先天信号的永生化细胞系过程中遇到的试验和困难，以及原代细胞的定向永生化如何避免自发永生化的许多陷阱。
