HERPES-SIMPLEX VIRUS TYPE-1 DNA PERSISTENCE, PROGRESSIVE DISEASE AND TRANSGENIC IMMEDIATE-EARLY GENE PROMOTER ACTIVITY IN CHRONIC CORNEAL INFECTIONS IN MICE

We have used a mouse model system and the corneal route of inoculation to examine the issue of extraneuronal persistence of herpes simplex v irus type 1 (HSV-1). HSV-1 strain F DNA and inflammatory lesions were detected in corneal tissue of mice at 5, 11, 23, 37 and 60 days post-i nfection (p.i.). Viral DNA was localized by in situ PCR to epithelial cells and less frequently to cells in the stroma of the cornea. Viral proteins were not detected in the cornea and virus could not be isolat ed from tissue homogenates after 11 days p.i. even though histopatholo gical lesions became progressively more severe at 37 and 60 days p.i. The DNA-containing cells were usually adjacent to the sites of inflamm ation or within these sites in the chronic stage (23, 37 and 60 days p .i.). In contrast to strain F, persistence of HSV-1 strain KOS DNA and inflammatory lesions were not detected after 11 days p.i.; this resul t suggests that the long-term persistence of HSV-1 DNA and the develop ment of inflammatory lesions are virus strain-dependent. We tested for the possibility of transgenic HSV-1 immediate early gene (ICP4) promo ter activity in chronically infected corneas of transgenic mice contai ning the ICP4 promoter fused to the bacterial beta-galactosidase codin g sequence. Our results indicated that the chimeric transgene was expr essed in the cornea at 5, 11, 23, 37 and 41 days p.i. Possible explana tions for these results and mechanisms for the generation of the chron ic inflammatory lesions are discussed. The properties of chronic HSV i nfections in the cornea may be similar to those which have been descri bed for persistent or defective viral infections in other systems.