title: Secreted herpes simplex virus-2 glycoprotein G alters thermal pain sensitivity by modifying NGF effects on TRPV1.
abstract: Genital herpes is a painful disease frequently caused by the neurotropic pathogen herpes simplex virus type 2 (HSV-2). We have recently shown that HSV-2-secreted glycoprotein G (SgG2) interacts with and modulates the activity of the neurotrophin nerve growth factor (NGF). This interaction modifies the response of the NGF receptor TrkA, increasing NGF-dependent axonal growth. NGF is not only an axonal growth modulator but also an important mediator of pain and inflammation regulating the amount, localization, and activation of the thermal pain receptor transient receptor potential vanilloid 1 (TRPV1). In this work, we addressed whether SgG2 could contribute to HSV-2-induced pain. Injection of SgG2 in the mouse hindpaw produced a rapid and transient increase in thermal pain sensitivity. At the molecular level, this acute increase in thermal pain induced by SgG2 injection was dependent on differential NGF-induced phosphorylation and in changes in the amount of TrkA and TRPV1 in the dermis. These results suggest that SgG2 alters thermal pain sensitivity by modulating TRPV1 receptor.
authors: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Nicolás Cabrera 1, Campus de Cantoblanco, E-28049, Madrid, Spain.|Centro de Investigaciones Biológicas en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Present address: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, 03766, USA.
authors: Jorge Rubén
authors: JR
authors: Cabrera
authors: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Nicolás Cabrera 1, Campus de Cantoblanco, E-28049, Madrid, Spain.|Present address: Institute of Virology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625, Hannover, Germany.
authors: Abel
authors: A
authors: Viejo-Borbolla
authors: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Nicolás Cabrera 1, Campus de Cantoblanco, E-28049, Madrid, Spain. aalcami@cbm.csic.es.
authors: Antonio
authors: A
authors: Alcamí
authors: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Nicolás Cabrera 1, Campus de Cantoblanco, E-28049, Madrid, Spain. fwandosell@cbm.csic.es.|Centro de Investigaciones Biológicas en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. fwandosell@cbm.csic.es.
authors: Francisco
authors: F
authors: Wandosell
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000633:toxicity*; D010146:Pain / Q000139:chemically induced* / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000633:toxicity*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014759:Viral Envelope Proteins; C045464:glycoprotein G, herpes simplex virus type 2; D020932:Nerve Growth Factor
keywords: Herpes infection; Inflammation; Pain sensitivity; Signaling