Reactivation of herpes simplex virus type 1 in the mouse trigeminal ganglion: an in vivo study of virus antigen and cytokines.
Reactivation of herpes simplex virus type 1 (HSV-1) in the trigeminal ganglion (TG) was induced by UV irradiation of the corneas of latently infected mice. Immunocytochemistry was used to monitor the dynamics of cytokine (interleukin-2 [IL-2], IL-4, IL-6, IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and viral antigen production in the TG and the adjacent central nervous system on days 1 to 4, 6, 7, and 10 after irradiation. UV irradiation induced increased expression of IL-6 and TNF-alpha from satellite cells in uninfected TG. In latently infected TG, prior to reactivation, all satellite cells were TNF-alpha+ and most were also IL-6(+). Reactivation, evidenced by HSV-1 antigens and/or infiltrating immune cells, occurred in 28 of 45 (62%) TG samples. Viral antigens were present in the TG in neurons, often disintegrating on days 2 to 6 after irradiation. Infected neurons were usually surrounded by satellite cells and the foci of immune cells producing TNF-alpha and/or IL-6. IL-4(+) cells were detected as early as day 3 and were more numerous by day 10 (a very few IL-2(+) and/or IFN-gamma+ cells were seen at this time). No IL-10 was detected at any time. Our observations indicate that UV irradiation of the cornea may modulate cytokine production by satellite cells. We confirm that neurons are the site of reactivation and that they probably do not survive this event. The predominance of TNF-alpha and IL-6 following reactivation parallels primary infection in the TG and suggests a role in viral clearance. The presence of Th2-type cytokines (IL-4 and IL-6) indicates a role for antibody. Thus, several clearance mechanisms may be at work.
Shimeld
C
C
Departments of Ophthalmology, University of Bristol, Bristol BS8 1TD, United Kingdom. C.Shimmeld@bris.ac.uk
Easty
D L
DL
Hill
T J
TJ
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D018259:Herpesvirus 1, Human / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D012668:Trigeminal Ganglion / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014466:Ultraviolet Rays; D014775:Virus Activation