Ocular herpes simplex virus reactivation in mice latently infected with latency-associated transcript mutants

Abstract

A mouse model for ocular reactivation of herpes simplex virus type 1 (HSV-1) was modified and used to study the effect of strain difference on the frequency of ocular HSV reactivation. Outbred male NIH white mice were immunized with 1.0 ml of anti-HSV serum with a neutralizing titer of 1:400 24 hr before infection and bilaterally infected at 10(5) plaque-forming units/eye with one of three HSV-1 strains: 17 Syn+, LAT+ (XC-20), or LAT- (X10-13). Latency-associated transcripts (LAT) are produced by strain 17 Syn+ and LAT+ but not by LAT-. The primary infection was monitored by ocular swabbing for HSV. Reactivation was induced by intravenous (i.v.) injection of cyclophosphamide (5 mg) followed 24 hr later by i.v. dexamethasone (0.2 mg). These drugs significantly reduced the white cell count between 0 and 6 days post-administration. The eyes were swabbed for 7 consecutive days to monitor reactivation, and HSV-1 reactivation was induced at the following frequencies in individual eyes: 17 Syn+ (32.5%), LAT+ (18.5%), and LAT- (2.5%) (P less than or equal to 0.002). Co-culture of trigeminal ganglia was done, and random isolates were checked to ascertain their identity. The HSV was recovered from individual trigeminal ganglia at the following frequencies: 17 Syn+ (83%), LAT+ (100%), and LAT- (67%) (P less than or equal to 0.091). These results confirm that the mouse can be used as a reactivation model for ocular HSV infection and that the presence of LAT facilitates reactivation in vivo in the mouse.