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Phosphonoacetic acid-resistant herpes simplex virus infection in hairless mice
Abstract:
Phosphonoacetic acid (PAA)-resistant type 1 herpes simplex virus population was isolated by repeated passage of the virus in the presence of this inhibitor. Hairless mice infected percutaneously with the inhibitor-resistant or the parental inhibitor-susceptible virus were treated intraperitoneally with PAA and 9-beta-d-arabinofuranosyl-adenine by using several different dosage schedules. Whereas 9-beta-d-arabinofuranosyl-adenine was effective both in the PAA-susceptible and PAA-resistant herpes simplex virus-induced skin infection, PAA suppressed only the infection induced by the parental PAA-susceptible virus.
Insights
Phosphonoacetic acid (PAA) resistance impacts herpes simplex virus (HSV) treatment. PAA effectively treated PAA-susceptible HSV infections, but not PAA-resistant strains in mice.
Area of Science:
- Virology
- Pharmacology
- Immunology
Background:
- Herpes simplex virus (HSV) infections are common worldwide.
- Antiviral drugs like phosphonoacetic acid (PAA) are used to treat HSV.
- Drug resistance can limit the efficacy of antiviral therapies.
Purpose of the Study:
- To investigate the efficacy of PAA against PAA-resistant HSV-1.
- To compare the effectiveness of PAA and 9-beta-d-arabinofuranosyl-adenine (ara-A) in treating HSV infections with varying PAA susceptibility.
- To evaluate antiviral treatment strategies in a preclinical animal model.
Main Methods:
- Isolation of a phosphonoacetic acid (PAA)-resistant herpes simplex virus type 1 (HSV-1) population through serial passage in vitro.
- Induction of skin infections in hairless mice using either PAA-susceptible or PAA-resistant HSV-1 strains.
- Intraperitoneal administration of PAA and 9-beta-d-arabinofuranosyl-adenine (ara-A) using diverse dosage regimens.
Main Results:
- 9-beta-d-arabinofuranosyl-adenine (ara-A) demonstrated efficacy against both PAA-susceptible and PAA-resistant HSV-1 skin infections.
- Phosphonoacetic acid (PAA) effectively suppressed infections caused by the parental PAA-susceptible HSV-1 strain.
- PAA failed to suppress infections caused by the isolated PAA-resistant HSV-1 population.
Conclusions:
- Development of PAA resistance in HSV-1 compromises the therapeutic effectiveness of PAA.
- Alternative antiviral agents like ara-A may retain efficacy against drug-resistant HSV strains.
- This study highlights the importance of monitoring antiviral resistance in HSV treatment strategies.