Mutagenesis of a cAMP response element within the latency-associated transcript promoter of HSV-1 reduces adrenergic reactivation.
Mutagenesis of a cyclic AMP response element (CRE) within the LAT promoter of HSV-1 reduces the ability of LAT expression to be induced in transient assays, but has only a minimal impact on reactivation of the virus in in vitro systems. Here we show that a CRE mutation results in a significant reduction of adrenergically induced reactivation in vivo in the rabbit eye model. Spontaneous reactivation frequencies were also reduced. In addition, we demonstrate that this mutation has no effect on the amount of LAT expressed during latency when compared with the parent, 17syn+, and the rescuant. These results indicate a greater effect of CRE on induced reactivation in vivo than in in vitro systems, but also suggest that the CRE in the LAT promoter is not autonomous in conducting the reactivation signal.
Bloom
D C
DC
Department of Microbiology, Arizona State University, Tempe, Arizona 85287, USA. dcbloom@asuvm.inre.asu.edu
Stevens
J G
JG
Hill
J M
JM
Tran
R K
RK
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers; D004279:DNA, Viral / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification*; D006561:Herpes Simplex; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011817:Rabbits; D018139:Simplexvirus / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D012867:Skin; D014158:Transcription, Genetic; D012668:Trigeminal Ganglion / Q000821:virology*; D014775:Virus Activation
D000199:Actins; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004279:DNA, Viral; D000242:Cyclic AMP