Abstract
Cells infected by herpes simplex virus type 1 in the G2 phase of the cell cycle become stalled at an unusual stage of mitosis defined as pseudoprometaphase. 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 stability of other centromere proteins may also be affected. Here, we demonstrate that ICP0 also induces the proteasome-dependent degradation of the centromere protein CENP-A. By a series of Western blot and immunofluorescence experiments we show that the endogenous 17-kDa CENP-A and an exogenous tagged version of CENP-A are lost from centromeres and degraded in infected and 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 the kinetochore. Unlike fully transcribed lytic viral DNA, the transcriptionally repressed latent herpes simplex virus type 1 genome has been reported to have a nucleosomal structure similar to that of cellular chromatin. Because ICP0 plays an essential part in controlling the balance between the lytic and latent outcomes of infection, the ICP0-induced degradation of CENP-A is an intriguing feature connecting different aspects of viral and/or cellular genome regulation.
Highlights
Herpes simplex virus type 1 (HSV-1)1 is a major human pathogen whose lifestyle is based on a long-term hide-and-seek interaction with the infected host
The detection of this protein by the human anti-centromere autoimmune (huACA) serum and its electrophoretic mobility were consistent with it being CENP-A. 17K/ CENP-A was not affected in cells infected by in1330, suggesting that ICP0 was implicated in the effect
A 15-kDa protein detected beneath 17K/CENP-A by huACA was detected by rabbit 554 and rabbit-L sera against CENP-C and CENP-B, respectively [21, 24], making it a protein nonspecifically recognized by at least three different sera directed against centromeric proteins
Summary
Herpes simplex virus type 1 (HSV-1)1 is a major human pathogen whose lifestyle is based on a long-term hide-and-seek interaction with the infected host. Because we did not expect to detect too many viral antigens at the low molecular weight range that would interfere with the detection of 17K/CENP-A, we performed Western blotting on HFL cells infected by HSV-1 viruses expressing the wild type (17ϩ) or the RING finger mutant (FXE) version of ICP0 and the ICP0-null mutant dl1403.
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