title: Herpes simplex virus type-1 latency-associated transcript-induced immunoreactivity of substance P in trigeminal neurons is reversed by bone morphogenetic protein-7.
abstract: Herpes simplex virus type-1 (HSV-1) primarily infects mucoepithelial tissues of the eye and the orofacial region. Subsequently, the virus is retrogradely transported through the axons of the trigeminal sensory neurons to their nuclei, where the virus establishes a life-long latent infection. During this latency period, the viral genome is transcriptionally silent except for a single region encoding the latency-associated transcript (LAT). To understand how HSV-1 latency might affect the expression of substance P in sensory neurons, we transfected primary cultures of trigeminal neurons obtained from rat embryos, with LAT expressing plasmids. The expression of LAT increased the percentage of substance P-immunoreactive neurons by two thirds. To examine the effect of bone morphogenetic protein-7 (BMP7) on the LAT-induced increase in substance P expression in trigeminal neurons, cultures transfected with LAT were treated with BMP7. Treatment with BMP7 reversed the effects of LAT on substance P expression in trigeminal neurons. Our data show for the first time that LAT increases substance P expression in trigeminal neurons and BMP7 can reverse these effects of LAT.
authors.affiliation: Departments of Pharmacology and Toxicology, University at Buffalo, SUNY, Buffalo, NY 14214, United States.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Hamza
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Higgins
authors.forename: William T
authors.initials: WT
authors.lastname: Ruyechan
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D013373:Substance P / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000166:cytology*; D017735:Virus Latency
chemical_list: C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins; D013373:Substance P