Abstract
BackgroundOthers and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral protein) against a wide range of viruses. The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (LCMV).MethodsWe examined the therapeutic effect of PAP in CBA mice inoculated with intracerebral injections of the WE54 strain of LCMV at a 1000 PFU dose level that is lethal to 100% of mice within 7–9 days. Mice were treated either with vehicle or PAP administered intraperitoneally 24 hours prior to, 1 hour prior to and 24 hours, 48 hours 72 hours and 96 hours after virus inoculation.ResultsPAP exhibits significant in vivo anti- LCMV activity in mice challenged intracerebrally with an otherwise invariably fatal dose of LCMV. At non-toxic dose levels, PAP significantly prolonged survival in the absence of the majority of disease-associated symptoms. The median survival time of PAP-treated mice was >21 days as opposed to 7 days median survival for the control (p = 0.0069).ConclusionOur results presented herein provide unprecedented experimental evidence that PAP exhibits antiviral activity in the CNS of LCMV-infected mice.
Highlights
Others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent pokeweed antiviral protein (PAP) (Pokeweed antiviral protein) against a wide range of viruses
Our results presented provide unprecedented experimental evidence that PAP exhibits antiviral activity in the central nervous system (CNS) of lymphocytic choriomeningitis virus (LCMV)-infected mice
In order to evaluate the anti-LCMV activity of PAP, mice were inoculated with intracerebral injections of LCMV at a dose level that is lethal to 100% of mice within 6–8 days
Summary
Others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral protein) against a wide range of viruses. The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (LCMV). The anti-viral activity of PAP has been described against a wide range of viruses, including HIV-1, herpes simplex virus, cytomegalovirus, influenza virus and polio virus [2] (For the most recent review, please see: [3]). The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on survival of mice challenged with intracerebral inoculations of lymphocytic choriomeningitis virus (LCMV). Aseptic meningitis or meningoenceophalitis are the predominant syndromes, transverse myelitis, a Guillain-Barre-type syndrome, as well as transient and permanent acquired hydrocephalus have been reported [47]
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