Stress up-regulates neuronal expression of the herpes simplex virus type 2 large subunit of ribonucleotide reductase (R1; ICP10) by activating activator protein 1.
Herpes simplex virus type 2 (HSV-2) genes expressed in neuronal cells in response to stress stimuli that trigger latency reactivation are largely unknown. Using a chloramphenicol acetyltransferase (CAT) reporter assay we found that stress caused a significant (P < .001) increase in ICP10 expression in neuronal cells. Up-regulation correlated with activator protein (AP)-1 activation, notably c-Jun and c-Fos that bind cognate elements in the ICP10 promoter. It was blocked by mutation of the AP-1 motifs in the ICP10 promoter. ICP10 expression protected neuronal cells from stress-induced apoptosis. The data suggest that ICP10 may contribute to HSV-2 reactivation by increasing neuronal survival.
Gober
Michael D
MD
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201-1559, USA.
Wales
Samantha Q
SQ
Hunter
J Colin
JC
Sharma
Bhuvnesh K
BK
Aurelian
Laure
L
D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D018869:Heat-Shock Response; D006558:Herpes Genitalis / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000235:genetics* / Q000254:growth & development; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000821:virology*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051381:Rats; D012264:Ribonucleotide Reductases / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015854:Up-Regulation
D018808:Transcription Factor AP-1; C100671:ICP10 protein, herpes simplex virus type 2; D012264:Ribonucleotide Reductases; D017346:Protein Serine-Threonine Kinases