PMID- 15039530
OWN - NLM
STAT- MEDLINE
DCOM- 20040504
LR  - 20200303
IS  - 0022-1317 (Print)
IS  - 0022-1317 (Linking)
VI  - 85
IP  - Pt 4
DP  - 2004 Apr
TI  - Productive human herpesvirus 6 infection causes aberrant accumulation of p53 and 
      prevents apoptosis.
PG  - 869-879
LID - 10.1099/vir.0.19626-0 [doi]
AB  - p53 plays an important role in tumour suppression in cells exposed to some 
      genotoxic stresses. We found that the p53 protein level was increased in a 
      variety of cell lines infected with human herpesvirus 6 (HHV-6). Because the 
      elevation in p53 began very soon after infection (4 h) and did not occur with 
      UV-inactivated virus infection, it appeared to require the expression of one or 
      more viral immediate-early (IE) genes. To elucidate the mechanism of p53 
      induction, we investigated its regulation at the protein level. Pulse-chase 
      analysis showed that the stability of p53 increased in HHV-6-infected cells. In 
      addition, the ubiquitination of p53 decreased after infection, indicating that 
      the stability of p53 was increased through deubiquitination. We showed by 
      confocal microscopy that the additional p53 mainly localized to the cytoplasm and 
      that p53 was retained in the cytoplasm even after UV irradiation, but that it 
      translocated into the nucleus in mock-infected cells. Furthermore, DNA 
      fragmentation analysis, a terminal deoxynucleotidyl transferase-mediated dUTP 
      nick end-labelling (TUNEL) assay and annexin V staining showed that infected 
      cells were resistant to UV-induced apoptosis. These results lead us to propose 
      that HHV-6 has a mechanism for retaining p53 within the cytoplasm and protects 
      the infected cells from apoptosis.
FAU - Takemoto, Masaya
AU  - Takemoto M
AD  - Department of Microbiology, Osaka University Medical School C1, 2-2 Yamada-Oka 
      Suita, Osaka 565-0871, Japan.
FAU - Mori, Yasuko
AU  - Mori Y
AD  - Department of Microbiology, Osaka University Medical School C1, 2-2 Yamada-Oka 
      Suita, Osaka 565-0871, Japan.
FAU - Ueda, Keiji
AU  - Ueda K
AD  - Department of Microbiology, Osaka University Medical School C1, 2-2 Yamada-Oka 
      Suita, Osaka 565-0871, Japan.
FAU - Kondo, Kazuhiro
AU  - Kondo K
AD  - Department of Microbiology, Osaka University Medical School C1, 2-2 Yamada-Oka 
      Suita, Osaka 565-0871, Japan.
FAU - Yamanishi, Koichi
AU  - Yamanishi K
AD  - Department of Microbiology, Osaka University Medical School C1, 2-2 Yamada-Oka 
      Suita, Osaka 565-0871, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (DNA, Viral)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Ubiquitin)
SB  - IM
MH  - Apoptosis/*physiology/radiation effects
MH  - Base Sequence
MH  - Cell Line
MH  - Cytoplasm/metabolism
MH  - DNA, Viral/genetics
MH  - Drug Stability
MH  - Gene Expression
MH  - Genes, Immediate-Early
MH  - Herpesvirus 6, Human/genetics/*pathogenicity/*physiology/radiation effects
MH  - Humans
MH  - Tumor Suppressor Protein p53/chemistry/*metabolism
MH  - Ubiquitin/metabolism
MH  - Ultraviolet Rays
EDAT- 2004/03/25 05:00
MHDA- 2004/05/05 05:00
CRDT- 2004/03/25 05:00
PHST- 2004/03/25 05:00 [pubmed]
PHST- 2004/05/05 05:00 [medline]
PHST- 2004/03/25 05:00 [entrez]
AID - 10.1099/vir.0.19626-0 [doi]
PST - ppublish
SO  - J Gen Virol. 2004 Apr;85(Pt 4):869-879. doi: 10.1099/vir.0.19626-0.