HERPES-SIMPLEX VIRUS TYPE-1 DNA PERSISTENCE, PROGRESSIVE DISEASE AND TRANSGENIC IMMEDIATE-EARLY GENE PROMOTER ACTIVITY IN CHRONIC CORNEAL INFECTIONS IN MICE
Wj. Mitchell et al., HERPES-SIMPLEX VIRUS TYPE-1 DNA PERSISTENCE, PROGRESSIVE DISEASE AND TRANSGENIC IMMEDIATE-EARLY GENE PROMOTER ACTIVITY IN CHRONIC CORNEAL INFECTIONS IN MICE, Journal of General Virology, 75, 1994, pp. 1201-1210
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.