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Research Article

Orofacial infection of athymic mice with defined mixtures of acyclovir-susceptible and acyclovir-resistant herpes simplex virus type 1.

M N Ellis, R Waters, E L Hill, D C Lobe, D W Selleseth, D W Barry
M N Ellis
Division of Virology, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709.
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R Waters
Division of Virology, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709.
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E L Hill
Division of Virology, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709.
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D C Lobe
Division of Virology, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709.
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D W Selleseth
Division of Virology, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709.
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D W Barry
Division of Virology, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709.
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DOI: 10.1128/AAC.33.3.304
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ABSTRACT

Infection of athymic mice with defined populations of acyclovir-susceptible (thymidine kinase [TK]-positive) and acyclovir-resistant (TK-deficient or TK-altered) herpes simplex virus type 1 strains was used to simulate herpetic skin disease of the immunocompromised host. In vitro characterization of the defined virus mixtures revealed that the dye uptake method was quite sensitive in the detection of small amounts (3 to 9%) of acylovir-resistant virus. Mice infected with homogeneous virus populations exhibited a good correlation between clinical response and the in vitro drug susceptibility of the infecting virus. Animals infected with defined mixtures of viruses exhibited varied patterns of infection and responses to acyclovir treatment. However, disease severity was useful in predicting the TK phenotype of virus recovered from lesions. Pathogenic, TK-altered virus was responsible for progressive disease in animals receiving low-dose (0.25-mg/ml) prophylactic acyclovir or high-dose (1.25-mg/ml) delayed therapy. Although this mutant was recovered infrequently, it was responsible for clinically significant disease in the animals from which it was isolated.

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Orofacial infection of athymic mice with defined mixtures of acyclovir-susceptible and acyclovir-resistant herpes simplex virus type 1.
M N Ellis, R Waters, E L Hill, D C Lobe, D W Selleseth, D W Barry
Antimicrobial Agents and Chemotherapy Mar 1989, 33 (3) 304-310; DOI: 10.1128/AAC.33.3.304

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Orofacial infection of athymic mice with defined mixtures of acyclovir-susceptible and acyclovir-resistant herpes simplex virus type 1.
M N Ellis, R Waters, E L Hill, D C Lobe, D W Selleseth, D W Barry
Antimicrobial Agents and Chemotherapy Mar 1989, 33 (3) 304-310; DOI: 10.1128/AAC.33.3.304
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