PMID- 9765424
OWN - NLM
STAT- MEDLINE
DCOM- 19981105
LR  - 20200724
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 72
IP  - 11
DP  - 1998 Nov
TI  - CD4 promoter transactivation by human herpesvirus 6.
PG  - 8797-805
AB  - The observation that human herpesvirus 6 (HHV-6) can induce CD4 gene 
      transcription and expression in CD4(-) cells was reported several years ago (P. 
      Lusso, A. De Maria, M. Malnati, F. Lori, S. E. DeRocco, M. Baseler, and R. C. 
      Gallo, Nature 349:533-535, 1991) and subsequently confirmed (P. Lusso, M. S. 
      Malnati, A. Garzino-Demo, R. W. Crowley, E. O. Long, and R. C. Gallo, Nature 
      362:458-462, 1993; G. Furlini, M. Vignoli, E. Ramazzotti, M. C. Re, G. Visani, 
      and M. LaPlaca, Blood 87:4737-4745, 1996). Our objective was to identify the 
      mechanisms underlying such phenomena. Using reporter gene constructs driven by 
      the CD4 promoter, we report that HHV-6 can efficiently transactivate such genetic 
      elements. Activation of the CD4 promoter occurs in the presence of the viral DNA 
      polymerase inhibitor phosphonoformic acid, which limits expression to the 
      immediate-early and early classes of viral genes. Using deletion mutants and 
      specific CD4 promoter mutants, we identified an ATF/CRE binding site located at 
      nucleotides -67 to -60 upstream of the CD4 gene transcription start site that is 
      important for HHV-6 transactivation. The ATF/CRE site is also essential for CD4 
      promoter activation by forskolin, an activator of adenylate cyclase. Using 
      electrophoretic mobility shift assays and specific antibodies, we showed that 
      CREB-1 binds specifically to the -79 to -52 region of the CD4 promoter. Last, we 
      have identified two open reading frames (ORFs) of HHV-6, U86 and U89 from the 
      immediate-early locus A, that can transactivate the CD4 promoter in HeLa cells. 
      However, transactivation of the CD4 promoter by ORFs U86 and U89 is independent 
      of the CRE element, suggesting that additional HHV-6 ORFs are likely to 
      contribute to CD4 gene activation. Taken together, our results will help to 
      understand the complex interactions occurring between HHV-6 and the CD4 promoter 
      and provide additional information regarding the class of transcription factors 
      involved in the control of CD4 gene expression.
FAU - Flamand, L
AU  - Flamand L
AD  - Laboratory of Virology, Rheumatology and Immunology Research Center, Centre de 
      Recherche du CHUL and Laval University, Sainte-Foy, Quebec, Canada. 
      louis.flamand@crchul.ulaval.ca
FAU - Romerio, F
AU  - Romerio F
FAU - Reitz, M S
AU  - Reitz MS
FAU - Gallo, R C
AU  - Gallo RC
LA  - eng
GR  - R03 AI41854-02/AI/NIAID 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.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CD4 Antigens)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (DNA Primers)
RN  - 0 (Transcription Factors)
RN  - 1F7A44V6OU (Colforsin)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - CD4 Antigens/*genetics
MH  - CD4-Positive T-Lymphocytes/immunology/virology
MH  - Cell Line
MH  - Colforsin/pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - DNA Primers/genetics
MH  - Genes, Viral
MH  - HIV Infections/etiology
MH  - HeLa Cells
MH  - Herpesvirus 6, Human/*genetics/*immunology/pathogenicity
MH  - Humans
MH  - Kinetics
MH  - Mutation
MH  - Open Reading Frames
MH  - Phosphorylation
MH  - *Promoter Regions, Genetic
MH  - Transcription Factors/metabolism
MH  - *Transcriptional Activation/drug effects
PMC - PMC110296
EDAT- 1998/10/10 00:00
MHDA- 1998/10/10 00:01
PMCR- 1998/11/01
CRDT- 1998/10/10 00:00
PHST- 1998/10/10 00:00 [pubmed]
PHST- 1998/10/10 00:01 [medline]
PHST- 1998/10/10 00:00 [entrez]
PHST- 1998/11/01 00:00 [pmc-release]
AID - 0290 [pii]
AID - 10.1128/JVI.72.11.8797-8805.1998 [doi]
PST - ppublish
SO  - J Virol. 1998 Nov;72(11):8797-805. doi: 10.1128/JVI.72.11.8797-8805.1998.