Increased severity of herpes simplex virus type 1-induced keratitis in Hox A5 transgenic mice.
OBJECTIVE
Herpes simplex virus type 1 is a major cause of stromal keratitis and blindness in humans. Understanding of the role of host genes in the pathogenesis of herpes stromal keratitis is limited. We used a transgenic mouse model to examine the effect of a host gene, Hox A5 (which binds to the TAATGARAT sequence in the promoter regions of HSV-1 immediate early genes and increases HSV-1 replication), on the pathogenesis of HSV-1 induced stromal keratitis.


METHODS
Corneas of wildtype and Hox A5 transgenic mice were infected with HSV-1 strain F following corneal scarification. Clinical severity of keratitis was evaluated using slit-lamp biomicroscopy. Histologic severity of keratitis was determined by light microscopic evaluation and by computerized morphometry. Ocular viral replication was measured via plaque assay.


RESULTS
Clinical lesions of stromal keratitis were more severe at 17 and 23 days post infection in Hox A5 transgenic mice than in wildtype mice. Histological evaluation and morphometric analysis confirmed that keratitis lesions were more severe in the transgenic mice. HSV-1 replication was approximately100-fold greater in the corneas of transgenic mice than in wildtype mice.


CONCLUSIONS
Our results demonstrate that a host gene (Hox A5) can increase ocular replication of HSV-1 and alter the pathogenesis of herpetic stromal keratitis.
Galle
L E
LE
Department of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
Taus
N S
NS
Maggs
D J
DJ
Moore
C P
CP
Mitchell
W J
WJ
D000818:Animals; D003319:Corneal Stroma / Q000473:pathology / Q000821:virology*; D015870:Gene Expression / Q000502:physiology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D016849:Keratitis, Herpetic / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010750:Phosphoproteins; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014779:Virus Replication / Q000235:genetics*
C489213:HOXA5 protein, human; D018398:Homeodomain Proteins; C059637:Hoxa5 protein, mouse; D010750:Phosphoproteins; D012367:RNA, Viral; D014157:Transcription Factors