title: Two alphaherpesvirus latency-associated gene products influence calcitonin gene-related peptide levels in rat trigeminal neurons.
abstract: Herpes simplex virus type-1 (HSV-1) initially infects mucoepithelial tissues of the eye and the orofacial region. Subsequently, the virus is retrogradely transported through the axons of the trigeminal sensory neurons. HSV-1 establishes a life-long latent infection in these neurons, during which the transcription of the viral genome is silent, except for the sequences encoding the latency-associated transcript (LAT). To determine if HSV-1 latency might affect calcitonin gene-related peptide (CGRP) expression in trigeminal sensory neurons, we transfected primary neuronal cultures of trigeminal ganglia from rat embryos with plasmids expressing LAT. In the presence of Bone Morphogenetic Protein-7 (BMP7), CGRP was expressed in 49% of sensory neurons. However, this percentage was reduced to 19% in neurons transfected with LAT expressing plasmids. We also found that transfection of the IE63 gene of varicella-zoster virus (VZV) reduced the percentage of trigeminal neurons containing CGRP. However, the observed effect of IE63 in contrast to that of LAT was completely reversed by treatment of cultures with MgCl2, which indicates that the effect of IE63 was due to increased release of CGRP from trigeminal neurons. We provide here the first evidence that HSV-1 LAT decreases the level of CGRP in trigeminal neurons. These effects may be important for reducing the neuroinflammatory response, thus protecting host neuronal cells during HSV-1 latency in trigeminal neurons. In contrast, increased release of CGRP in the presence of IE63 protein may contribute to the neuralgias associated with VZV infection.
authors.affiliation: Department of Pharmacology and Toxicology, SUNY, Buffalo, NY 14214, USA.
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; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology / Q000821:virology; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology; D006561:Herpes Simplex / Q000503:physiopathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D015636:Magnesium Chloride / Q000494:pharmacology; D035683:MicroRNAs; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology / Q000821:virology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000166:cytology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics*; D017735:Virus Latency / Q000502:physiology
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004279:DNA, Viral; D017874:Immediate-Early Proteins; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C074551:immediate early protein 63, Human herpesvirus 3; C477253:latency associated transcript, herpes simplex virus-1; D015636:Magnesium Chloride; D015740:Calcitonin Gene-Related Peptide