The effects of aminoguanidine on primary and recurrent ocular herpes simplex virus infection.
In primary ocular herpes simplex virus (HSV) infection, nitric oxide may function to control viral replication and herpetic stromal keratitis (HSK) lesions. Recurrent HSK, manifested as corneal opacity and neovascularization, is the potentially blinding sequel to primary infection. Here, we assess the effects of nitric oxide synthase inhibition on a mouse model of recurrent HSK. In preliminary primary infection experiments, NIH inbred mice treated with aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), experienced no changes in post-infection tear, brain, or ganglia virus titers, but encephalitis-related mortality was elevated. After UV-B stimulated viral reactivation, iNOS inhibition did not affect virus shedding or clinical disease. In contrast to primary HSK, there was no exacerbation of mortality in recurrent disease. Our findings indicate that nitric oxide can be neuroprotective without antiviral effects in primary HSK, and does not play a significant role in the pathogenesis of recurrent HSK. Compared with data from other mouse strains, this work suggests that there may be a genetic component to the importance of NO in controlling ocular HSV infection.
Keadle
Tammie L
TL
Washington University School of Medicine, Department of Ophthalmology Visual Sciences, 660 S. Euclid, Box 8096, St. Louis, MO 63110, USA. keadle@vision.wustl.edu
Morris
Jessica L
JL
Stuart
Patrick M
PM
D000818:Animals; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D006561:Herpes Simplex / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology* / Q000821:virology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012008:Recurrence; D018139:Simplexvirus / Q000502:physiology*; D015996:Survival Rate
D006146:Guanidines; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine