Roos D S, Duchala C S, Stephensen C B, Holmes K V, Choppin P W
Laboratory of Virology, Rockefeller University, New York, New York 10021.
Virology. 1990 Apr;175(2):345-57. doi: 10.1016/0042-6822(90)90419-r.
Virus-induced cell fusion has been examined in a series of stable cell lines which were originally selected for resistance to the fusogenic effects of polyethylene glycol (PEG). For a wide variety of viruses, including murine hepatitis virus (a coronavirus), vesicular stomatitis virus (a rhabdovirus), and two paramyxoviruses (Sendai virus and SV5), susceptibility to virus-induced fusion was found to be inversely correlated with susceptibility to PEG-induced fusion. This phenomenon was observed both for cell fusion occurring in the course of viral infection and for fusion induced "from without" by the addition of high titers of noninfectious or inactivated virus. The fusion-altered cell lines (fusible by virus but not by PEG) are characterized by their unusual lipid composition, including marked elevation of saturated fatty acids and the presence of an unusual ether-linked neutral lipid. To test the association between lipid composition and fusion, acyl chain saturation was manipulated by supplementing the culture medium with exogenous fatty acids. In such experiments, it was possible to control the responses of these cells to both viral and chemical fusogens. Increasing the cellular content of saturated fatty acyl chains increased the susceptibility of cells to viral fusion and decreased susceptibility to PEG-induced fusion, whereas lowering fatty acid saturation had the opposite effect. Thus, parallel cultures of cells can be either driven toward the PEG-fusible/virus-fusion-resistant phenotype of the parental cells or rendered susceptible to viral fusion but resistant to PEG-induced fusion, solely by the alteration of cellular lipids. The ability of cellular lipid composition to regulate virus-induced membrane fusion suggests a possible role for lipids in viral infection and pathogenesis.
在一系列最初因对聚乙二醇（PEG）的融合作用具有抗性而被筛选出的稳定细胞系中，对病毒诱导的细胞融合进行了研究。对于多种病毒，包括鼠肝炎病毒（一种冠状病毒）、水泡性口炎病毒（一种弹状病毒）以及两种副粘病毒（仙台病毒和SV5），发现对病毒诱导融合的易感性与对PEG诱导融合的易感性呈负相关。这种现象在病毒感染过程中发生的细胞融合以及通过添加高滴度的非感染性或灭活病毒“从外部”诱导的融合中均有观察到。融合改变的细胞系（可被病毒融合但不能被PEG融合）的特征在于其异常的脂质组成，包括饱和脂肪酸显著升高以及存在一种异常的醚连接中性脂质。为了测试脂质组成与融合之间的关联，通过在培养基中添加外源性脂肪酸来操纵酰基链饱和度。在这类实验中，可以控制这些细胞对病毒和化学融合剂的反应。增加饱和脂肪酰链的细胞含量会增加细胞对病毒融合的易感性，并降低对PEG诱导融合的易感性，而降低脂肪酸饱和度则会产生相反的效果。因此，仅通过改变细胞脂质，细胞的平行培养物可以被驱动向亲代细胞的PEG可融合/病毒融合抗性表型，或者使其对病毒融合敏感但对PEG诱导融合具有抗性。细胞脂质组成调节病毒诱导膜融合的能力表明脂质在病毒感染和发病机制中可能发挥作用。
