title: Tranylcypromine reduces herpes simplex virus 1 infection in mice.
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.
authors.affiliation: Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Yao
authors.forename: Pin-Hung
authors.initials: PH
authors.lastname: Lin
authors.forename: Fang-Hsiu
authors.initials: FH
authors.lastname: Shen
authors.forename: Guey-Chuen
authors.initials: GC
authors.lastname: Perng
authors.forename: Yuk-Ying
authors.initials: YY
authors.lastname: Tung
authors.forename: Sheng-Min
authors.initials: SM
authors.lastname: Hsu
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D006561:Herpes Simplex / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000378:metabolism; D014191:Tranylcypromine / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D014191:Tranylcypromine; D013937:Thymidine Kinase