Herpes simplex virus type 1 latency in the murine nervous system is associated with oxidative damage to neurons.
The pathological consequences of herpes simplex virus type 1 (HSV-1) latency in the nervous system are not well understood. To determine whether acute and latent HSV-1 infections of the nervous system are associated with oxidative damage, mice were inoculated with HSV-1 by the corneal route, and the extent of viral infection and oxidative damage in trigeminal ganglia and brain was assessed at 7, 90, and 220 days after inoculation. Abundant HSV-1 protein expression in the nervous system was observed in neurons and non-neuronal cells at 7 days after inoculation, consistent with viral replication and spread through the trigeminal and olfactory systems. Acute HSV-1 infection was associated with focal, neuronal and non-neuronal 4-hydroxy-2-nonenal- and 8-hydroxyguanosine-specific immunoreactivity, indicating oxidative damage. Rare HSV-1 antigen-positive cells were observed at 90 and 220 days after inoculation; however, widespread HSV-1 latency-associated transcript expression was detected, consistent with latent HSV-1 infection in the nervous system. HSV-1 latency was detected predominantly in the trigeminal ganglia, brainstem, olfactory bulbs, and temporal cortex. Latent HSV-1 infection was associated with focal chronic inflammation and consistently detectable evidence of oxidative damage involving primarily neurons. These results indicate that both acute and latent HSV-1 infections in the murine nervous system are associated with oxidative damage.
Valyi-Nagy
T
T
Departments of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Olson
S J
SJ
Valyi-Nagy
K
K
Montine
T J
TJ
Dermody
T S
TS
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology / Q000821:virology*; D001933:Brain Stem / Q000473:pathology / Q000821:virology; D005260:Female; D006561:Herpes Simplex / Q000473:pathology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000473:pathology / Q000821:virology*; D009830:Olfactory Bulb / Q000473:pathology / Q000821:virology; D013702:Temporal Lobe / Q000473:pathology / Q000821:virology; D012668:Trigeminal Ganglion / Q000473:pathology / Q000821:virology*; D010948:Viral Plaque Assay; D017735:Virus Latency