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Herpes Simplex Acyclovir-Resistant Mutant in Experimental Keratouveitis
Helene M. Boisjoly, MD, FRCS(C);
No-Hee Park, DMD, PhD;
Deborah Pavan-Langston, MD;
Erik De Clercq, MD, PhD
Arch Ophthalmol. 1983;101(11):1782-1786.
Abstract
Acyclovir is a potent and selective antiviral agent. Unfortunately, drug-resistant (acyclovir-resistant) mutants have already been reported in herpes simplex virus type 1 (HSV-1) orofacial infections. We have developed a laboratory acyclovir-resistant HSV-1 mutant. The natural course of acyclovir-resistant HSV-1 keratitis was found to be less virulent than that observed in wild type HSV-1 keratitis, but the rate of ganglionic latency was as high as that induced by the parental strain. In vitro studies and in vivo observation of rabbit corneas infected with acyclovir-resistant HSV-1 both demonstrated a significant sensitivity to vidarabine and bromovinyldeoxyuridine ([E]-5-[2-bromovinyl]-2'-deoxyuridine). The thymidine kinase activity of the acyclovir-resistant mutant was 69% of that of the wild type HSV-1.
Author Affiliations
From the Cornea Research Department of the Eye Research Institute of Retina Foundation (Drs Boisjoly, Park, and Pavan-Langston), and the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston (Drs Boisjoly, Park, and Pavan-Langston), and the Rega Institute of Medical Research, University of Leuven, Leuven, Belgium (Dr De Clercq).
Footnotes
Accepted for publication Oct 23, 1982.
Read in part before the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla, May 4, 1982.
Reprint requests to 20 Staniford St, Boston, MA 02114 (Dr Park).
This investigation was supported in part by a Centennial fellowship grant of the Medical Research Council of Canada (H.M.B.), a grant from the National Societv to Prevent Blindness (H.M.B.), research grants NIDR-05572 (N.H.P. and D.P.L.) and EYNS-02268 (D.P.L. and N.H.P.), and the Prince Charitable Trusts (D.P.L.).
Patricia A. Geary and Yong Ki Chung gave technical assistance. The bromovinyldeoxyuridine was synthesized by R. Brisson and H. Vanderhaeghe at the Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
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