Spontaneous reactivation of herpes simplex virus type 1 in latently infected murine sensory ganglia.
Careful studies of mouse trigeminal ganglia (TG) latently infected with herpes simplex virus type 1 (HSV-1) indicate the presence of productive cycle viral gene products and persistent immune response, suggesting ongoing spontaneous viral reactivation in these tissues. In the present study we set out to determine whether infectious virus is present in murine TG latently infected with HSV-1 (KOS). At 37 days after ocular inoculation we found a small amount of infectious virus in ca. 6% of latently infected murine TG. Furthermore, the amount of infectious virus that we detected (PFU per viral antigen-positive neuron) was similar to that detected in acutely infected ganglia. We conclude that spontaneous reactivation of infectious HSV-1 occurs in the mouse TG and is likely the principle cause of viral protein expression in these tissues. We next examined the role of latency-associated transcript (LAT) in spontaneous ganglionic reactivation by examining ganglia latently infected with KOS dlLAT1.8, a LAT deletion virus. Through the use of immunocytochemistry we found that KOS dlLAT1.8 had a rate of spontaneous ganglionic reactivation very similar to that of HSV-1 (KOS). Studying spontaneous ganglionic reactivation of HSV in the mouse TG allows a direct study of viral reactivation from latently infected neurons without the potential confounders and complicating downstream events that accompany the study of viral reactivation by explantation or peripheral viral shedding. Since most cases of human viral shedding and reactivation are not associated with a known trigger, spontaneous ganglionic reactivation of HSV-1 may be a better model of human disease than existing models.
Margolis
Todd P
TP
Francis I. Proctor Foundation, UCSF, Medical Sciences Building S-310, 513 Parnassus Ave., San Francisco, CA 94143-0412, USA. todd.margolis@ucsf.edu
Elfman
Fred L
FL
Leib
David
D
Pakpour
Nazzy
N
Apakupakul
Kathleen
K
Imai
Yumi
Y
Voytek
Cindy
C
D000818:Animals; D017950:Ganglia, Sensory / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D051379:Mice; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics; D014775:Virus Activation; D017735:Virus Latency
D014764:Viral Proteins