Retinoic acid receptors initiate induction of the cytomegalovirus enhancer in embryonal cells.
Reactivation of latent virus is believed to result from a signal transduction event that induces immediate-early (IE) gene transcription. Evidence is presented that the major IE promoter (MIEP) of human cytomegalovirus (hCMV) is activated by physiological levels of retinoic acid (RA) in human embryonal carcinoma cells. Mutagenesis experiments localized in the MIEP enhancer, a retinoic acid-responsive element composed of a direct repeat separated by five nucleotides. Protein-DNA binding experiments revealed that this element functions as a specific target site for the direct interaction of nuclear receptor proteins for RA. These findings implicate the biologically active derivative of vitamin A (RA) as a potential modulator of hCMV pathogenesis in infants and immunocompromised adults.
Ghazal
P
P
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
DeMattei
C
C
Giulietti
E
E
Kliewer
S A
SA
Umesono
K
K
Evans
R M
RM
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D003587:Cytomegalovirus / Q000235:genetics* / Q000502:physiology; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014763:Viral Matrix Proteins / Q000235:genetics; D014775:Virus Activation
D000956:Antigens, Viral; D002352:Carrier Proteins; D017874:Immediate-Early Proteins; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; C044582:immediate-early proteins, cytomegalovirus