Tranylcypromine Reduces Herpes Simplex Virus 1 Infection in Mice.

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, 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), the 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, the
infection of 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.

No comments: