Eclipse phase of herpes simplex virus type 1 infection:: Efficient dynein-mediated capsid transport without the small capsid protein VP26
Eclipse phase of herpes simplex virus type 1 infection:: Efficient dynein-mediated capsid transport without the small capsid protein VP26
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DOI：
10.1128/jvi.02528-05
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发表时间：
2006-08-01
影响因子：
5.4
通讯作者：
Sodeik, Beate
中科院分区：
文献类型：
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作者：
Doehner, Katinka;Radtke, Kerstin;Sodeik, Beate
胞浆动力蛋白与其辅助因子动力蛋白一起，将传入的单纯疱疹病毒I型衣壳沿微管(MT)运送到MT组织中心(MTOC)。衣壳从MTOC进一步移动到核孔，在那里病毒基因组被释放到核质中。小衣壳蛋白VP26可以与动力蛋白轻链Tctex 1(DYNLT1)和RP3(DYNLT3)相互作用，并可能将动力蛋白招募到衣壳中。因此，我们分析了不含VP26的HSV1-Delta VP26衣壳和表达GFPVP26融合而不是VP26的HSV1-GFPVP26衣壳的核靶向性。为了比较不同菌株的细胞进入情况，我们从传染性、病毒基因组含量、蛋白质组成和颗粒组成等方面对接种物进行了表征。低颗粒与PFU比率的制剂显示出有效的核靶向，并且被认为比含有许多缺陷颗粒的制剂质量更高，后者无法诱导斑块形成。当HSV-1野生型、HSV1-Delta VP26或HSV1-GFPVP26感染细胞时，病毒衣壳沿MT转运至细胞核。此外，当dynein功能被dynactin亚基Dynamitin过表达抑制时，HSV-1野生型、HSV1-Delta VP26和HSV1-GFPVP26衣壳到达细胞核的数量较少。因此，即使在没有潜在的病毒动力蛋白受体VP26的情况下，HSV-1也使用MT和动力蛋白进行有效的核靶向。这些数据表明，除了VP26，HSV-1还编码其他动力蛋白或动力蛋白受体。
Cytoplasmic dynein,together with its cofactor dynactin, transports incoming herpes simplex virus type I (HSV-1) capsids along microtubulles (MT) to the MT-organizing center (MTOC). From the MTOC, capsids move further to the nuclear pore, where the viral genome is released into the nucleoplasm. The small capsid protein VP26 can interact with the dynein light chains Tctex1 (DYNLT1) and rp3 (DYNLT3) and may recruit dynein to the capsid. Therefore, we analyzed nuclear targeting of incoming HSV1-Delta VP26 capsids devoid of VP26 and of HSV1-GFPVP26 capsids expressing a GFPVP26 fusion instead of VP26. To compare the cell entry of different strains, we characterized the inocula with respect to infectivity, viral genome content, protein composition, and particle composition. Preparations with a low particle-to-PFU ratio showed efficient nuclear targeting and were considered to be of higher quality than those containing many defective particles, which were unable to induce plaque formation. When cells were infected with HSV-1 wild type, HSV1-Delta VP26, or HSV1-GFPVP26, viral capsids were transported along MT to the nucleus. Moreover, when dynein function was inhibited by overexpression of the dynactin subunit dynamitin, fewer capsids of HSV-1 wild type, HSV1-Delta VP26, and HSV1-GFPVP26 arrived at the nucleus. Thus, even in the absence of the potential viral dynein receptor VP26, HSV-1 used MT and dynein for efficient nuclear targeting. These data suggest that besides VP26, HSV-1 encodes other receptors for dynein or dynactin.