PMID- 17913805
OWN - NLM
STAT- MEDLINE
DCOM- 20071227
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 81
IP  - 24
DP  - 2007 Dec
TI  - Human herpesvirus 6A (HHV-6A) and HHV-6B alter E2F1/Rb pathways and E2F1 
      localization and cause cell cycle arrest in infected T cells.
PG  - 13499-508
AB  - E2F transcription factors play pivotal roles in controlling the expression of 
      genes involved in cell viability as well as genes involved in cell death. E2F1 is 
      an important constituent of this protein family, which thus far contains eight 
      members. The interaction of E2F1 with its major regulator, retinoblastoma protein 
      (Rb), has been studied extensively in the past two decades, concentrating on the 
      role of E2F1 in transcriptional regulation and the role of Rb in cell replication 
      and cancer formation. Additionally, the effect of viral infections on E2F1/Rb 
      interactions has been analyzed for different viruses, concentrating on cell 
      division, which is essential for viral replication. In the present study, we 
      monitored E2F1-Rb interactions during human herpesvirus 6A (HHV-6A) and HHV-6B 
      infections of SupT1 T cells. The results have shown the following dramatic 
      alterations in E2F1-Rb pathways compared to the pathways of parallel 
      mock-infected control cultures. (i) The E2F1 levels were elevated during viral 
      infections. (ii) The cellular localization of E2F1 was dramatically altered, and 
      it was found to accumulate both in the cytoplasmic and nuclear fractions, as 
      opposed to the strict nuclear localization seen in the mock-infected cells. (iii) 
      Although E2F1 expression was elevated, two exemplary target genes, cyclin E and 
      MCM5, were not upregulated. (iv) The Rb protein was dephosphorylated early 
      postinfection, a trait that also occurred with UV-inactivated virus. (v) 
      Infection was associated with significant reduction of E2F1/Rb complexing. (vi) 
      HHV-6 infections were accompanied by cell cycle arrest. The altered E2F1-Rb 
      interactions and functions might contribute to the observed cell cycle arrest.
FAU - Mlechkovich, Guy
AU  - Mlechkovich G
AD  - The S. Daniel Abraham Institute for Molecular Virology and the Department of Cell 
      Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
FAU - Frenkel, Niza
AU  - Frenkel N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071003
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (E2F1 Transcription Factor)
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Cell Cycle/*drug effects
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cytoplasm/metabolism
MH  - E2F1 Transcription Factor/genetics/*metabolism/pharmacology
MH  - *Gene Expression Regulation
MH  - Herpesvirus 6, Human/*pathogenicity/radiation effects
MH  - Humans
MH  - Retinoblastoma Protein/genetics/*metabolism
MH  - T-Lymphocytes/*virology
MH  - Ultraviolet Rays
PMC - PMC2168879
EDAT- 2007/10/05 09:00
MHDA- 2007/12/28 09:00
PMCR- 2008/04/01
CRDT- 2007/10/05 09:00
PHST- 2007/10/05 09:00 [pubmed]
PHST- 2007/12/28 09:00 [medline]
PHST- 2007/10/05 09:00 [entrez]
PHST- 2008/04/01 00:00 [pmc-release]
AID - JVI.01496-07 [pii]
AID - 1496-07 [pii]
AID - 10.1128/JVI.01496-07 [doi]
PST - ppublish
SO  - J Virol. 2007 Dec;81(24):13499-508. doi: 10.1128/JVI.01496-07. Epub 2007 Oct 3.