TY - JOUR
T1 - Cytoplasmic sequestration of p53 in cytomegalovirus-infected human endothelial cells
AU - Kovacs, Andras
AU - Weber, Marc L
AU - Burns, Linda J.
AU - Jacob, Harry S
AU - Vercellotti, Gregory M
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1996/11
Y1 - 1996/11
N2 - Human umbilical vein endothelial cells were infected with human cytomegalovirus (HCMV) at a multiplicity of infection of 0.1 plaque-forming unit/cell and remained >95% viable even after 10 days of infection. To induce apoptosis, control human umbilical vein endothelial cells and cells infected with HCMV for 3, 5, and 7 days were serum starved for 48 hours. Almost one- half of the uninfected cells lost viability after 48 hours of serum starvation whereas HCMV-infected cells were virtually unaffected (<20% death, P < 0.05). Uninfected cells showed typical hallmarks of apoptosis, including unique morphological changes and DNA laddering. HCMV-infected cells, concomitant with their resistance to serum-starvation-induced death, displayed almost none of these characteristics. Active replication of HCMV was necessary for the anti-apoptotic effect, as cells treated with ultraviolet-light-inactivated virus were not protected. p53, the G1/S phase cell cycle brake protein, was elevated in HCMV-infected cells. However, rather than accumulating in the nucleus, immunofluorescent and Western blot studies demonstrated remarkable and predominant cytoplasmic sequestration of p53 in HCMV-infected endothelial cells. Although HCMV proteins have already been shown to block apoptosis, we suggest that the aberrant subcellular pattern of p53 is the disturbed cellular mechanism that may be responsible for the anti-apoptotic properties of HCMV-infected cells. The selective resistance to apoptosis can be important during HCMV replication and may explain the oncogenic potential of HCMV as well as its pathogenic role in intimal-proliferation-mediated vascular diseases.
AB - Human umbilical vein endothelial cells were infected with human cytomegalovirus (HCMV) at a multiplicity of infection of 0.1 plaque-forming unit/cell and remained >95% viable even after 10 days of infection. To induce apoptosis, control human umbilical vein endothelial cells and cells infected with HCMV for 3, 5, and 7 days were serum starved for 48 hours. Almost one- half of the uninfected cells lost viability after 48 hours of serum starvation whereas HCMV-infected cells were virtually unaffected (<20% death, P < 0.05). Uninfected cells showed typical hallmarks of apoptosis, including unique morphological changes and DNA laddering. HCMV-infected cells, concomitant with their resistance to serum-starvation-induced death, displayed almost none of these characteristics. Active replication of HCMV was necessary for the anti-apoptotic effect, as cells treated with ultraviolet-light-inactivated virus were not protected. p53, the G1/S phase cell cycle brake protein, was elevated in HCMV-infected cells. However, rather than accumulating in the nucleus, immunofluorescent and Western blot studies demonstrated remarkable and predominant cytoplasmic sequestration of p53 in HCMV-infected endothelial cells. Although HCMV proteins have already been shown to block apoptosis, we suggest that the aberrant subcellular pattern of p53 is the disturbed cellular mechanism that may be responsible for the anti-apoptotic properties of HCMV-infected cells. The selective resistance to apoptosis can be important during HCMV replication and may explain the oncogenic potential of HCMV as well as its pathogenic role in intimal-proliferation-mediated vascular diseases.
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M3 - Article
C2 - 8909243
AN - SCOPUS:0029957281
SN - 0002-9440
VL - 149
SP - 1531
EP - 1539
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -