A Preclinical Model for Studying Herpes Simplex Virus Infection.
J Invest Dermatol
; 139(3): 673-682, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30414908
ABSTRACT
Herpes simplex virus (HSV) infections can cause considerable morbidity. Currently, nucleoside analogues such as acyclovir are widely used for treatment. However, HSV infections resistant to these drugs are a clinical problem among immunocompromised patients. To provide more efficient therapy and to counteract resistance, a different class of antiviral compounds has been developed. Pritelivir, a helicase primase inhibitor, represents a promising candidate for improved therapy. Here, we established an HSV-1 infection model on microneedle-pretreated human skin ex vivo. We identified HSV-1-specific histological changes (e.g., cytopathic effects, multinucleated giant cells), down-regulation of nectin-1, nuclear translocation of NF-κB (p65), interferon regulatory factor 3 (IRF3), and signaling of the IFN-inducible protein MxA. Accordingly, this model was used to test the potency of pritelivir compared with the standard drug acyclovir. We discovered that both drugs had a comparable efficacy for inhibiting HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir-resistant strains. To our knowledge, we present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Replicação Viral
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Herpesvirus Humano 1
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Herpes Simples
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Áustria