Elevation of cyclic AMP levels in cell lines derived from latently infectable sensory neurons increases their permissivity for herpes virus infection by activating the viral immediate-early 1 gene promoter.
Immortalized cell lines derived from sensory neurons are relatively non-permissive for lytic infection with herpes simplex virus (HSV) and fail to transcribe the viral immediate-early genes following infection. Treatment of these cells with agents which raise the intra-cellular level of cyclic AMP results in increased activity of the IE1 gene which contains a cyclic AMP response element within its promoter and produces a consequent increase in permissivity for HSV infection. The significance of these effects for the regulation of HSV infection of neuronal cells are discussed in the light of the finding that cyclic AMP treatment can reactivate latent HSV infections.
Department of Biochemistry, University College and Middlesex School of Medicine, London, U.K.
S C
SC
Wheatley
C L
CL
Dent
J N
JN
Wood
D S
DS
Latchman
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D017456:Adenovirus Early Proteins; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002472:Cell Transformation, Viral; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000378:metabolism; D005814:Genes, Viral; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D018139:Simplexvirus / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D017456:Adenovirus Early Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D015292:Glycoprotein Hormones, alpha Subunit; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase; D015056:1-Methyl-3-isobutylxanthine