PMID- 10398670
OWN - NLM
STAT- MEDLINE
DCOM- 19990803
LR  - 20220408
IS  - 0893-8512 (Print)
IS  - 1098-6618 (Electronic)
IS  - 0893-8512 (Linking)
VI  - 12
IP  - 3
DP  - 1999 Jul
TI  - Human cytomegalovirus and human herpesvirus 6 genes that transform and 
      transactivate.
PG  - 367-82
AB  - This review is an update on the transforming genes of human cytomegalovirus 
      (HCMV) and human herpesvirus 6 (HHV-6). Both viruses have been implicated in the 
      etiology of several human cancers. In particular, HCMV has been associated with 
      cervical carcinoma and adenocarcinomas of the prostate and colon. In vitro 
      transformation studies have established three HCMV morphologic transforming 
      regions (mtr), i.e., mtrI, mtrII, and mtrIII. Of these, only mtrII (UL111A) is 
      retained and expressed in both transformed and tumor-derived cells. The 
      transforming and tumorigenic activities of the mtrII oncogene were localized to 
      an open reading frame (ORF) encoding a 79-amino-acid (aa) protein. Furthermore, 
      mtrII protein bound to the tumor suppressor protein p53 and inhibited its ability 
      to transactivate a p53-responsive promoter. In additional studies, the HCMV 
      immediate-early protein IE86 (IE2; UL122) was found to interact with cell 
      cycle-regulatory proteins such as p53 and Rb. However, IE86 exhibited 
      transforming activity in vitro only in cooperation with adenovirus E1A. HHV-6 is 
      a T-cell-tropic virus associated with AIDS-related and other lymphoid 
      malignancies. In vitro studies identified three transforming fragments, i.e., 
      SalI-L, ZVB70, and ZVH14. Of these, only SalI-L (DR7) was retained in transformed 
      and tumor-derived cells. The transforming and tumorigenic activities of SalI-L 
      have been localized to a 357-aa ORF-1 protein. The ORF-1 protein was expressed in 
      transformed cells and, like HCMV mtrII, bound to p53 and inhibited its ability to 
      transactivate a p53-responsive promoter. HHV-6 has also been proposed to be a 
      cofactor in AIDS because both HHV-6 and human immunodeficiency virus type 1 
      (HIV-1) have been demonstrated to coinfect human CD4(+) T cells, causing 
      accelerated cytopathic effects. Interestingly, like the transforming proteins of 
      DNA tumor viruses such as simian virus 40 and adenovirus, ORF-1 was also a 
      transactivator and specifically up-regulated the HIV-1 long terminal repeat when 
      cotransfected into CD4(+) T cells. Finally, based on the interactions of HCMV and 
      HHV-6 transforming proteins with tumor suppressor proteins, a scheme is proposed 
      for their role in oncogenesis.
FAU - Doniger, J
AU  - Doniger J
AD  - Department of Microbiology and Immunology, Georgetown University Medical Center, 
      Washington, D.C. 20007, USA.
FAU - Muralidhar, S
AU  - Muralidhar S
FAU - Rosenthal, L J
AU  - Rosenthal LJ
LA  - eng
GR  - P30 CA051008/CA/NCI NIH HHS/United States
GR  - CA 60577/CA/NCI NIH HHS/United States
GR  - P30 CA51008-09/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Clin Microbiol Rev
JT  - Clinical microbiology reviews
JID - 8807282
RN  - 0 (HLA-DR7 Antigen)
RN  - 0 (IE2 protein, Cytomegalovirus)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Trans-Activators)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (UL115 protein, Human herpesvirus 5)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (Viral Proteins)
RN  - 0 (glycoprotein H, Cytomegalovirus)
RN  - 0 (glycoprotein H, Human cytomegalovirus)
RN  - 0 (glycoprotein O, cytomegalovirus)
SB  - IM
MH  - Cell Transformation, Viral/genetics
MH  - Cytomegalovirus/*genetics
MH  - Genes, Viral/genetics
MH  - Genome, Viral
MH  - HIV-1/genetics
MH  - HLA-DR7 Antigen/genetics/metabolism
MH  - Herpesvirus 6, Human/*genetics
MH  - Humans
MH  - Immediate-Early Proteins/metabolism
MH  - *Membrane Glycoproteins
MH  - Neoplasms/virology
MH  - Oncogenes/genetics
MH  - Open Reading Frames
MH  - Retinoblastoma Protein/metabolism
MH  - T-Lymphocytes/virology
MH  - *Trans-Activators
MH  - Tumor Suppressor Protein p53/metabolism
MH  - *Viral Envelope Proteins
MH  - Viral Proteins/metabolism
PMC - PMC100243
EDAT- 1999/07/10 00:00
MHDA- 1999/07/10 00:01
PMCR- 1999/07/01
CRDT- 1999/07/10 00:00
PHST- 1999/07/10 00:00 [pubmed]
PHST- 1999/07/10 00:01 [medline]
PHST- 1999/07/10 00:00 [entrez]
PHST- 1999/07/01 00:00 [pmc-release]
AID - 0021 [pii]
AID - 10.1128/CMR.12.3.367 [doi]
PST - ppublish
SO  - Clin Microbiol Rev. 1999 Jul;12(3):367-82. doi: 10.1128/CMR.12.3.367.