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Antimicrobial Agents and Chemotherapy, July 1998, p. 1555-1562, Vol. 42, No. 7
Centre for Veterinary Science, Cambridge
University Veterinary School, Cambridge, United Kingdom
Received 22 October 1997/Returned for modification 6 January
1998/Accepted 3 April 1998
Famciclovir (FCV) and valaciclovir (VACV) have previously been
shown to be potent inhibitors of herpes simplex virus type 1 (HSV-1) in
a murine cutaneous model. In the present study, mice were inoculated in
the skin of the left ear pinna with herpes simplex virus (HSV) type 1. Antiviral therapy was started on different days postinoculation (p.i.),
terminating at the end of day 10 p.i. The compounds were
administered twice daily by oral gavage at 50 mg/kg of body
weight/dose. Mice were sampled on day 5 p.i., during the acute
phase of the infection, and the titers of infectious virus in the
target tissues (ear, brain stem, and trigeminal ganglia) were
determined. At 2 to 3 months p.i., the ipsilateral and contralateral trigeminal and cervical dorsal root ganglia were explanted, and four
different methods were used to detect latent HSV. The methods were (i)
conventional explant culture for 5 days followed by homogenization, (ii) long-term culture (up to 73 days) of whole ganglia, followed by
homogenization, (iii) dissociation by enzymatic disaggregation and an
infectious center assay, and (iv) in situ hybridization to detect
latency-associated transcripts (LATs). The conventional explant culture
method was the least sensitive method, while in situ staining for LAT
was the most sensitive, and all mice, including those treated from
early times with FCV, were shown to be latently infected. Significantly
less latent virus was detected by all four methods, however, in ganglia
obtained from mice that had been treated with FCV in comparison with
the amount detected in ganglia from mice that had been treated with
VACV. However, in no case was latency completely eliminated.
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Famciclovir and Valaciclovir Differ in the
Prevention of Herpes Simplex Virus Type 1 Latency in Mice: a
Quantitative Study
*
Corresponding author. Mailing address: Centre for
Veterinary Science, Cambridge University Veterinary School, Madingley
Road, Cambridge CB3 OES, United Kingdom. Phone: (44) 01223 330810. Fax: (44) 01223 332998. E-mail: hjf10{at}cam.ac.uk.
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