Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110

Examination of cells at the early stages of herpes simplex virus type 1 inf ection revealed that the viral immediate-early protein Vmw110 (also known a s ICP0) formed discrete punctate accumulations associated with centromeres in both mitotic and interphase cells. The RING finger domain of Vmw110 (but not the C-terminaI region) was essential for its localization at centromer es, thus distinguishing the Vmw110 sequences required for centromere associ ation from those required for its localization at other discrete nuclear st ructures known as ND10, promyelocytic leukaemia (PML) bodies or PODs, We ha ve shown recently that Vmw110 can induce the proteasome-dependent loss of s everal cellular proteins, including a number of probable SUMO-1-conjugated isoforms of PML, anti: this results in the disruption of ND10. In this stud y, we found some striking similarities between the interactions of Vmw110 w ith ND10 and centromeres, Specifically, centromeric protein CENP-C was lost from centromeres during virus infection in a Vmw110- and proteasome-depend ent manner, causing substantial ultrastructural changes in the kinetochore. In consequence, dividing cells either became stalled in mitosis or underwe nt an unusual cytokinesis resulting in daughter cells with many micronuclei . These results emphasize the importance of CENP-C for mitotic progression and suggest that Vmw110 may be interfering with biochemical mechanisms whic h are relevant to both centromeres and ND10.