Garcin Pierre O, Nabi Ivan R, Panté Nelly
Department of Zoology, University of British Columbia, Vancouver, BC, Canada.
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
Virology. 2015 Jul;481:63-72. doi: 10.1016/j.virol.2015.02.019. Epub 2015 Mar 11.
Galectin-3 has previously been found to be required by the parvovirus minute virus of mice prototype strain (MVMp) for infection of mouse fibroblast cells. Since MVMp is an oncotropic virus, and galectin-3 is a multifunctional protein implicated in cancer metastasis, we hypothesized that galectin-3 and Mgat5, the Golgi enzyme that synthesizes high-affinity glycan ligands of galectin-3, might play a role in MVMp infection. Using siRNA-mediated knockdown of galectin-3 in mouse cells transformed with polyomavirus middle T antigen and Mgat5(-/-) mouse mammary tumor cells, we found that galectin-3 and Mgat5 are both necessary for efficient MVMp cell entry and infection, but not for cell binding. Moreover, we found that human cancer cells expressing higher levels of galectin-3 were more efficiently infected with MVMp than cell lines expressing lower galectin-3 levels. We conclude that galectin-3 and Mgat5 are involved in MVMp infection, and propose that galectin-3 is a determinant of MVMp oncotropism.
此前已发现，小鼠细小病毒原型株（MVMp）感染小鼠成纤维细胞需要半乳糖凝集素-3。由于MVMp是一种亲肿瘤病毒，且半乳糖凝集素-3是一种与癌症转移有关的多功能蛋白，我们推测半乳糖凝集素-3和Mgat5（合成半乳糖凝集素-3高亲和力聚糖配体的高尔基体酶）可能在MVMp感染中发挥作用。利用RNA干扰介导的方法，在经多瘤病毒中T抗原转化的小鼠细胞和Mgat5基因敲除（Mgat5(-/-)）的小鼠乳腺肿瘤细胞中敲低半乳糖凝集素-3，我们发现半乳糖凝集素-3和Mgat5对于MVMp高效进入细胞并感染细胞都是必需的，但对于细胞结合则不是必需的。此外，我们发现，表达较高水平半乳糖凝集素-3的人癌细胞比表达较低水平半乳糖凝集素-3的细胞系更易被MVMp感染。我们得出结论，半乳糖凝集素-3和Mgat5参与了MVMp感染，并提出半乳糖凝集素-3是MVMp亲肿瘤性的一个决定因素。
