Cytokine-mediated survival from lethal herpes simplex virus infection: role of programmed neuronal death.
The mechanisms responsible for cytokine-mediated antiviral effects are not fully understood. We approached this problem by studying the outcome of intraocular herpes simplex (HSV) infection in transgenic mice that express interferon gamma in the photoreceptor cells of the retina. These transgenic mice showed selective survival from lethal HSV-2 infection manifested in both eyes, the optic nerve, and the brain. Although transgenic mice developed greater inflammatory responses to the virus in the eyes, inflammation and viral titers in their brains were equivalent to nontransgenic mice. However, survival of transgenic mice correlated with markedly lower numbers of central neurons undergoing apoptosis. The protooncogene Bcl2 was found to be induced in the HSV-2-infected brains of transgenic mice, allowing us to speculate on its role in fostering neuronal survival in this model. These observations imply a complex interaction between cytokine, virus, and host cellular factors. Our results suggest a cytokine-regulated salvage pathway that allows for survival of infected neurons.
Geiger
K D
KD
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Gurushanthaiah
D
D
Howes
E L
EL
Lewandowski
G A
GA
Reed
J C
JC
Bloom
F E
FE
Sarvetnick
N E
NE
D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis; D001921:Brain / Q000473:pathology*; D005123:Eye / Q000166:cytology / Q000276:immunology; D015828:Eye Infections, Viral; D006561:Herpes Simplex / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018259:Herpesvirus 1, Human / Q000472:pathogenicity; D018258:Herpesvirus 2, Human / Q000472:pathogenicity; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012160:Retina / Q000821:virology; D016019:Survival Analysis; D015854:Up-Regulation
D015703:Antigens, CD; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D007371:Interferon-gamma