Pathogenesis of acyclovir-resistant herpes simplex type 2 isolates in animal models of genital herpes

Models for antiviral evaluations

David I. Bernstein, Jim Ireland, Nigel Bourne

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Our understanding of the pathogenesis of acyclovir (ACV)-resistant herpes simplex virus (HSV) is limited, especially with regard to reactivation and recurrent disease. To further explore the pathogenesis of ACV-resistant HSV-2 viruses, we used the guinea pig model of genital HSV-2 infection to evaluate several ACV-resistant isolates of both thymidine kinase (Tk)-altered and Tk-deficient phenotypes obtained from HIV-infected patients. Two plaque- purified workpools from each isolate were initially evaluated. Each produced acute disease and at least one clinical recurrence. The two strains that produced the most severe primary disease and most recurrences, one Tk- deficient virus and one Tk-altered virus, were further evaluated and shown to produce acute and recurrent genital disease similar to that seen with wild- type viruses. Furthermore, the reactivated virus producing recurrent lesions could be a pure population with minimal Tk activity. Finally, we showed that topical foscarnet treatment could alter disease and vaginal virus replication following vaginal inoculation with these two ACV-resistant strains. Using the guinea pig model of genital HSV-2 infection, we found that recurrent disease following infection with markedly Tk-deficient viruses was more common than expected, especially in select isolates. Furthermore, this model should be useful in evaluating potential new therapies for ACV-resistant HSV strains. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)159-169
Number of pages11
JournalAntiviral Research
Volume47
Issue number3
DOIs
StatePublished - Sep 2000
Externally publishedYes

Fingerprint

Herpes Genitalis
Herpes Simplex
Acyclovir
Thymidine Kinase
Antiviral Agents
Animal Models
Viruses
Human Herpesvirus 2
Virus Diseases
Simplexvirus
Vaginal Diseases
Guinea Pigs
Foscarnet
Recurrence
Acute Disease
Virus Replication
HIV
Phenotype
Therapeutics
Infection

Keywords

  • Acyclovir resistant
  • Animal models
  • Genital herpes
  • Pathogenesis

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

Pathogenesis of acyclovir-resistant herpes simplex type 2 isolates in animal models of genital herpes : Models for antiviral evaluations. / Bernstein, David I.; Ireland, Jim; Bourne, Nigel.

In: Antiviral Research, Vol. 47, No. 3, 09.2000, p. 159-169.

Research output: Contribution to journalArticle

@article{0c49d4696382451cba5364ff6b5eb778,
title = "Pathogenesis of acyclovir-resistant herpes simplex type 2 isolates in animal models of genital herpes: Models for antiviral evaluations",
abstract = "Our understanding of the pathogenesis of acyclovir (ACV)-resistant herpes simplex virus (HSV) is limited, especially with regard to reactivation and recurrent disease. To further explore the pathogenesis of ACV-resistant HSV-2 viruses, we used the guinea pig model of genital HSV-2 infection to evaluate several ACV-resistant isolates of both thymidine kinase (Tk)-altered and Tk-deficient phenotypes obtained from HIV-infected patients. Two plaque- purified workpools from each isolate were initially evaluated. Each produced acute disease and at least one clinical recurrence. The two strains that produced the most severe primary disease and most recurrences, one Tk- deficient virus and one Tk-altered virus, were further evaluated and shown to produce acute and recurrent genital disease similar to that seen with wild- type viruses. Furthermore, the reactivated virus producing recurrent lesions could be a pure population with minimal Tk activity. Finally, we showed that topical foscarnet treatment could alter disease and vaginal virus replication following vaginal inoculation with these two ACV-resistant strains. Using the guinea pig model of genital HSV-2 infection, we found that recurrent disease following infection with markedly Tk-deficient viruses was more common than expected, especially in select isolates. Furthermore, this model should be useful in evaluating potential new therapies for ACV-resistant HSV strains. (C) 2000 Elsevier Science B.V.",
keywords = "Acyclovir resistant, Animal models, Genital herpes, Pathogenesis",
author = "Bernstein, {David I.} and Jim Ireland and Nigel Bourne",
year = "2000",
month = "9",
doi = "10.1016/S0166-3542(00)00104-2",
language = "English (US)",
volume = "47",
pages = "159--169",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Pathogenesis of acyclovir-resistant herpes simplex type 2 isolates in animal models of genital herpes

T2 - Models for antiviral evaluations

AU - Bernstein, David I.

AU - Ireland, Jim

AU - Bourne, Nigel

PY - 2000/9

Y1 - 2000/9

N2 - Our understanding of the pathogenesis of acyclovir (ACV)-resistant herpes simplex virus (HSV) is limited, especially with regard to reactivation and recurrent disease. To further explore the pathogenesis of ACV-resistant HSV-2 viruses, we used the guinea pig model of genital HSV-2 infection to evaluate several ACV-resistant isolates of both thymidine kinase (Tk)-altered and Tk-deficient phenotypes obtained from HIV-infected patients. Two plaque- purified workpools from each isolate were initially evaluated. Each produced acute disease and at least one clinical recurrence. The two strains that produced the most severe primary disease and most recurrences, one Tk- deficient virus and one Tk-altered virus, were further evaluated and shown to produce acute and recurrent genital disease similar to that seen with wild- type viruses. Furthermore, the reactivated virus producing recurrent lesions could be a pure population with minimal Tk activity. Finally, we showed that topical foscarnet treatment could alter disease and vaginal virus replication following vaginal inoculation with these two ACV-resistant strains. Using the guinea pig model of genital HSV-2 infection, we found that recurrent disease following infection with markedly Tk-deficient viruses was more common than expected, especially in select isolates. Furthermore, this model should be useful in evaluating potential new therapies for ACV-resistant HSV strains. (C) 2000 Elsevier Science B.V.

AB - Our understanding of the pathogenesis of acyclovir (ACV)-resistant herpes simplex virus (HSV) is limited, especially with regard to reactivation and recurrent disease. To further explore the pathogenesis of ACV-resistant HSV-2 viruses, we used the guinea pig model of genital HSV-2 infection to evaluate several ACV-resistant isolates of both thymidine kinase (Tk)-altered and Tk-deficient phenotypes obtained from HIV-infected patients. Two plaque- purified workpools from each isolate were initially evaluated. Each produced acute disease and at least one clinical recurrence. The two strains that produced the most severe primary disease and most recurrences, one Tk- deficient virus and one Tk-altered virus, were further evaluated and shown to produce acute and recurrent genital disease similar to that seen with wild- type viruses. Furthermore, the reactivated virus producing recurrent lesions could be a pure population with minimal Tk activity. Finally, we showed that topical foscarnet treatment could alter disease and vaginal virus replication following vaginal inoculation with these two ACV-resistant strains. Using the guinea pig model of genital HSV-2 infection, we found that recurrent disease following infection with markedly Tk-deficient viruses was more common than expected, especially in select isolates. Furthermore, this model should be useful in evaluating potential new therapies for ACV-resistant HSV strains. (C) 2000 Elsevier Science B.V.

KW - Acyclovir resistant

KW - Animal models

KW - Genital herpes

KW - Pathogenesis

UR - http://www.scopus.com/inward/record.url?scp=0033814075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033814075&partnerID=8YFLogxK

U2 - 10.1016/S0166-3542(00)00104-2

DO - 10.1016/S0166-3542(00)00104-2

M3 - Article

VL - 47

SP - 159

EP - 169

JO - Antiviral Research

JF - Antiviral Research

SN - 0166-3542

IS - 3

ER -