Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
Virology. 2010 Jun 5;401(2):266-79. doi: 10.1016/j.virol.2010.02.027. Epub 2010 Mar 24.
Myxoma (MYXV) and vaccinia (VACV) viruses have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1--low-pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2--the tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3--knockdown of PAK1 revealed that it is required for a late stage event downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms.
粘液瘤病毒（MYXV）和牛痘病毒（VACV）最近已成为有潜力的溶瘤病毒，可感染并杀死不同的人类癌细胞。虽然它们在结构上相似，但尚不清楚这些痘病毒进入并导致癌细胞发生溶瘤的途径是否在机制上相似。在这里，我们比较了 MYXV 和 VACV-WR 进入各种人类癌细胞的过程，观察到了显著的差异：1. 低 pH 值处理加速了 VACV 的融合介导进入，但对 MYXV 没有影响；2. 酪氨酸激酶抑制剂金雀异黄素抑制了 VACV 的进入，但对 MYXV 没有影响；3. PAK1 的敲低显示其在 MYXV 进入癌细胞的晚期事件中是必需的，而 PAK1 是 VACV 进入相同靶细胞所必需的。这些结果表明，VACV 和 MYXV 利用不同的机制进入人类癌细胞，因此为它们在不同的肿瘤细胞趋向性方面提供了一些依据。
