PMID- 7745731
OWN - NLM
STAT- MEDLINE
DCOM- 19950613
LR  - 20200724
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 69
IP  - 6
DP  - 1995 Jun
TI  - Retinoid activation of retinoic acid receptors but not of retinoid X receptors 
      promotes cellular differentiation and replication of human cytomegalovirus in 
      embryonal cells.
PG  - 3831-7
AB  - The susceptibility of human embryonal cell line NT-2/D1 to replicate human 
      cytomegalovirus (hCMV) is dependent on retinoic acid (RA) stimulation. 
      Physiological responses to retinoic acid involve two distinct subfamilies of 
      nuclear receptors, the RA receptors (RARs) and retinoid X receptors (RXRs), which 
      function by activating transcription as heterodimeric or RXR homodimeric 
      complexes from cis-acting DNA response elements. At present, it is not clear 
      whether the association between these two classes of receptors can lead to 
      multiple distinct induction pathways by signalling one or both receptor partners. 
      Here we have determined, by selectively activating endogenous receptors with 
      novel synthetic ligands specific for either RARs or RXRs, what ligand interaction 
      is physiological in the retinoid receptor pathways necessary for inducing 
      replication of hCMV in differentiated embryonal cells. We show that ligand 
      binding to RAR alone is sufficient and that exclusive ligand activation of RXR is 
      insufficient for inducing replication of hCMV. We also find that differentiation 
      and inhibition of NT-2/D1 cell growth are promoted by compounds that signal the 
      RAR pathway. These results provide direct evidence that RAR ligand-mediated 
      physiological responses are separable and distinct from RXR ligand activation 
      functions. Moreover, our results provide insight into a hormone response pathway 
      for cellular differentiation that might be coopted by hCMV in the host.
FAU - Angulo, A
AU  - Angulo A
AD  - Department of Immunology, Scripps Research Institute, La Jolla, California 92037, 
      USA.
FAU - Suto, C
AU  - Suto C
FAU - Boehm, M F
AU  - Boehm MF
FAU - Heyman, R A
AU  - Heyman RA
FAU - Ghazal, P
AU  - Ghazal P
LA  - eng
GR  - N01-HD-2-3144/HD/NICHD 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 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - *Cell Differentiation
MH  - Cell Division
MH  - Cell Line
MH  - Cytomegalovirus/*physiology
MH  - Embryo, Mammalian/cytology
MH  - Humans
MH  - Receptors, Retinoic Acid/*drug effects
MH  - Retinoid X Receptors
MH  - Retinoids/*pharmacology
MH  - Signal Transduction
MH  - Transcription Factors/*drug effects
MH  - *Virus Replication
PMC - PMC189101
EDAT- 1995/06/01 00:00
MHDA- 1995/06/01 00:01
PMCR- 1995/06/01
CRDT- 1995/06/01 00:00
PHST- 1995/06/01 00:00 [pubmed]
PHST- 1995/06/01 00:01 [medline]
PHST- 1995/06/01 00:00 [entrez]
PHST- 1995/06/01 00:00 [pmc-release]
AID - 10.1128/JVI.69.6.3831-3837.1995 [doi]
PST - ppublish
SO  - J Virol. 1995 Jun;69(6):3831-7. doi: 10.1128/JVI.69.6.3831-3837.1995.