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H. S. Toma, G. Singh, D. M. Neumann, P. S. Bhattacharjee, S. Bouhnik, H. E. Kaufman, J. M. Hill; Spontaneous Shedding of HSV-1 DNA of High and Low Phenotypic Reactivating Strains in the Rabbit Eye Model Support an Emerging Paradigm. Invest. Ophthalmol. Vis. Sci. 2008;49(13):493. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Early models of HSV-1 latency emphasized the "dormant" state of the virus in neurons. Our previous studies have shown that certain strains of HSV-1 shed infectious virus (1) spontaneously, (2) at a high frequency after induction by Iontophoresis, (3) induced corneal epithelial lesions spontaneously, and (4) induced epithelial lesions at high frequency, hence referred to as high phenotypic reactivators (HPR). Low phenotypic reactivators (LPR) on the other hand had opposite effects. Detection of HSV-1 DNA in tears using PCR showed that a high percentage of humans and animals latent with HSV-1 spontaneously and asymptomatically shed the virus at a high frequency, yet the incidence of herpetic eye disease was low. Our objective was to determine the spontaneous shedding of HSV-1 DNA by rabbit eyes latently infected with different viral strains to correlate the frequency of HSV-1 DNA shedding to the reactivation phenotypes. These data will be valuable in understanding the relationship between HSV-1 strains and the development and prevention of ocular disease.
The eyes of New Zealand White rabbits were inoculated with HSV-1 strains McKrae, dLAT2903, 17Syn+, 17 Δpst, KOS (M), KOS Δ29 LAT and RE. Corneal infections were confirmed by slit-lamp examination. Rabbit eye swabs were collected as early as postinfection (PI) day 21 and as late as PI day 93. DNA was extracted from swabs and quantified for HSV-1 DNA using real time PCR.
Both HPR and LPR shed HSV-1 DNA at high frequencies. The frequencies ranged from 87-100% of swabs tested and had no specific pattern. In general, HPR shed HSV-1 DNA at higher copy numbers compared to the LPR.
HSV-1 latent rabbits shed viral DNA at a high frequency, similar to humans. These data also suggest that the status of latency is "active" rather than "dormant". The frequency of shedding and copy number could provide an insight into the ocular pathogenesis of HSV-1.
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