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Xiaodong Zheng, Mary E. Marquart, Jeannette M. Loustch, Pulin Shah, Bruno Sainz, Arnab Ray, Richard J. O’Callaghan, Herbert E. Kaufman, James M. Hill; HSV-1 Migration in Latently Infected and Naive Rabbits after Penetrating Keratoplasty. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2490-2497.
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purpose. To investigate the migration of herpes simplex virus type 1 (HSV-1)
between latently infected and naive corneal tissues and trigeminal
ganglion (TG) in rabbits after penetrating keratoplasty (PKP) and
transcorneal epinephrine iontophoresis.
methods. Two mutants, genetically constructed from HSV-1 strain
17syn +, were used to inoculate rabbit
corneas: 17ΔPst, a latency associated transcript (LAT) negative,
low-reactivating virus and 17Pr, a high-reactivating, LAT-positive
rescuant of 17ΔPst. Latently infected rabbits were given
corneal allografts from naive rabbits, and naive rabbits received
grafts from latently infected rabbits. Ninety days after PKP, groups of
the transplanted rabbits were induced to reactivate by transcorneal
epinephrine iontophoresis, but others were not induced. Viral shedding
was monitored by tear film cultures. Rabbits were killed 5 days after
iontophoresis. Transplanted grafts, recipient corneal rims, and
corresponding TG were obtained. Nucleic acids were extracted and
amplified for detection of HSV-1 DNA and viral gene transcription.
results. In naive rabbits receiving grafts transplanted from rabbits latently
infected with 17Pr (LAT+), 3 of 6 corneal rims contained
HSV DNA after induction. In contrast, none of the 5 corneal rims from
naive rabbits receiving grafts from rabbits latent with 17ΔPst
(LAT−) contained viral DNA. Viral DNA and gene transcripts
were detected in 2 of 6 TG from naive rabbits that received grafts from
17Pr (LAT+) latently infected rabbits. In recipient corneal
rims and TG of latently infected rabbits receiving grafts from naive
rabbits, viral DNA concentration was significantly greater with induced
reactivation, compared with the results in noninduced rabbits. The
amount of viral DNA in naive grafts transplanted into 17Pr
(LAT+) latently infected rabbits was significantly higher
with induction than without induction (P = 0.018).
More viral DNA and viral gene transcripts were found in tissues from
rabbits latently infected with 17Pr (LAT+) than in rabbits
latently infected with 17ΔPst (LAT−).
conclusions. Corneas from latently infected rabbits contain HSV-1 DNA that can
replicate after induced reactivation. Viral migration can occur in both
anterograde and retrograde directions between the transplanted graft
and the recipient corneal rim and TG. The LAT negative HSV-1 construct
17ΔPst has a significantly reduced ability to replicate and
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