Capsaicin-induced reactivation of latent herpes simplex virus type 1 in sensory neurons in culture.
Herpes simplex virus type 1 (HSV-1) produces a life-long latent infection in neurons of the peripheral nervous system, primarily in the trigeminal and dorsal root ganglia. Neurons of these ganglia express high levels of the capsaicin receptor, also known as the vanilloid receptor-1 (VR-1). VR-1 is a non-selective ion channel, found on sensory neurons, that primarily fluxes Ca(2+) ions in response to various stimuli, including physiologically acidic conditions, heat greater than 45 degrees C and noxious compounds such as capsaicin. Using an in vitro neuronal model to study HSV-1 latency and reactivation, we found that agonists of the VR-1 channel - capsaicin and heat - resulted in reactivation of latent HSV-1. Capsaicin-induced reactivation of HSV-1 latently infected neurons was dose-dependent. Additionally, activation of VR-1 at its optimal temperature of 46 degrees C caused a significant increase in virus titres, which could be attenuated with the VR-1 antagonist, capsazepine. VR-1 activation that resulted in HSV-1 reactivation was calcium-dependent, since the calcium chelator BAPTA significantly reduced reactivation following treatment with caspsaicin and forskolin. Taken together, these results suggest that activation of the VR-1 channel, often associated with increases in intracellular calcium, results in HSV-1 reactivation in sensory neurons.
Hunsperger
Elizabeth A
EA
Department of Microbiology, Colorado State University, 200 West Lake Street, Ft Collins, CO 80523, USA.
Wilcox
Christine L
CL
Department of Microbiology, Colorado State University, 200 West Lake Street, Ft Collins, CO 80523, USA.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006358:Hot Temperature; D009475:Neurons, Afferent / Q000821:virology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency
D011955:Receptors, Drug; D002211:Capsaicin; D002118:Calcium