Tranylcypromine reduces herpes simplex virus 1 infection in mice

Hui Wen Yao, Pin Hung Lin, Fang Hsiu Shen, Guey Chuen Perng, Yuk Ying Tung, Sheng Min Hsu, Shun Hua Chen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Herpes simplex virus 1 (HSV-1) infects the majority of the human population and establishes latency by maintaining viral genomes in neurons of sensory ganglia. Latent virus can undergo reactivation to cause recurrent infection. Both primary and recurrent infections can cause devastating diseases, including encephalitis and corneal blindness. Acyclovir is used to treat patients, but virus resistance to acyclovir is frequently reported. Recent in vitro findings reveal that pretreatment of cells with tranylcypromine (TCP), a drug widely used in the clinic to treat neurological disorders, restrains HSV-1 gene transcription by inhibiting the histone-modifying enzyme lysine-specific demethylase 1. The present study was designed to examine the anti-HSV-1 efficacy of TCP in vivo because of the paucity of reports on this issue. Using the murine model, we found that TCP decreased the severity of wild-type-virus- induced encephalitis and corneal blindness, infection with the acyclovir-resistant (thymidine kinase-negative) HSV-1 mutant, and tissue viral loads. Additionally, TCP blocked in vivo viral reactivation in trigeminal ganglia. These results support the therapeutic potential of TCP for controlling HSV-1 infection.

Original languageEnglish
Pages (from-to)2807-2815
Number of pages9
JournalAntimicrobial agents and chemotherapy
Volume58
Issue number5
DOIs
Publication statusPublished - 2014 May

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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