Impaired Fas-Fas Ligand Interactions Result in Greater Recurrent Herpetic Stromal Keratitis in Mice.
Herpes simplex virus-1 (HSV-1) infection of the cornea leads to a potentially blinding condition termed herpetic stromal keratitis (HSK). Clinical studies have indicated that disease is primarily associated with recurrent HSK following reactivation of a latent viral infection of the trigeminal ganglia. One of the key factors that limit inflammation of the cornea is the expression of Fas ligand (FasL). We demonstrate that infection of the cornea with HSV-1 results in increased functional expression of FasL and that mice expressing mutations in Fas (lpr) and FasL (gld) display increased recurrent HSK following reactivation compared to wild-type mice. Furthermore, both gld and lpr mice took longer to clear their corneas of infectious virus and the reactivation rate for these strains was significantly greater than that seen with wild-type mice. Collectively, these findings indicate that the interaction of Fas with FasL in the cornea restricts the development of recurrent HSK.
Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Xiao-Tang
XT
Yin
Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Tammie L
TL
Keadle
Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Jessicah
J
Hard
Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
John
J
Herndon
Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Chloe A
CA
Potter
Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Chelsea R
CR
Del Rosso
Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Thomas A
TA
Ferguson
Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Patrick M
PM
Stuart
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003315:Cornea / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D016679:Genome, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D016849:Keratitis, Herpetic / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011485:Protein Binding; D012008:Recurrence; D019562:Viral Load; D014775:Virus Activation / Q000276:immunology / Q000528:radiation effects; D017201:Virus Shedding; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D000914:Antibodies, Viral; D053222:Fas Ligand Protein; D019014:fas Receptor