Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0

Cells infected by herpes simplex virus type 1 in the G(2) phase of the cell cycle become stalled at an unusual stage of mitosis defined as pseudoprome taphase, This block correlates with the viral immediate-early protein ICP0- induced degradation of the centromere protein CENP-C. However, the observed pseudoprometaphase phenotype of infected mitotic cells suggests that the s tability of other centromere proteins may also be affected. Here, we demons trate that ICP0 also induces the proteasome-dependent degradation of the ce ntromere protein CENP-A. By a series of Western blot and immunofluorescence experiments we show that the endogenous 17-kDa CENP-A and an exogenous tag ged version of CENP A are lost from centromeres and degraded in infected an d transfected cells as a result of ICP0 expression. CENP-A is a histone H3- like protein associated with nucleosome structures in the inner plate of th e kinetochore. Unlike fully transcribed lytic viral DNA, the transcriptiona lly repressed latent herpes simplex virus type 1 genome has been reported t o have a nucleosomal structure similar to that of cellular chromatin, Becau se ICP0 plays an essential part in controlling the balance between the lyti c and latent outcomes of infection, the ICP0-induced degradation of CENP-A is an intriguing feature connecting different aspects of viral and/or cellu lar genome regulation.