title: Lovastatin delays infection and increases survival rates in AG129 mice infected with dengue virus serotype 2.
abstract: BACKGROUND
  It has been reported that treatment of DENV-infected cultures with Lovastatin (LOV), can affect viral assembly. The objective of this study was to evaluate the effect of LOV on the survival rate and viremia levels of DENV-2-infected AG129 mice.
  
  
  RESULTS
  Mice were inoculated with 1 × 10(6) plaque-forming units (PFU/ml) of DENV-2 and treated with LOV (200 mg/kg/day). Pre-treatment with one or three doses of LOV increased the survival rate compared to untreated mice (7.3 and 7.1 days, respectively, compared to 4.8 days). Viremia levels also decreased by 21.8% compared to untreated mice, but only in the group administered three doses prior to inoculation. When LOV was administered after viral inoculation, the survival rate increased (7.3 days in the group treated at 24 hpi, 6.8 days in the group treated at 48 hpi and 6.5 days in the group treated with two doses) compared to the untreated group (4.8 days). Interestingly, the serum viral titer increased by 24.6% in mice treated at 48 hpi with a single dose of LOV and by 21.7% in mice treated with two doses (at 24 and 48 hpi) of LOV compared to untreated mice. Finally histopathological changes in the liver and spleen in infected and untreated mice included massive extramedullary erythropoiesis foci and inflammatory filtration, and these characteristics were decreased or absent in LOV-treated mice.
  
  
  CONCLUSIONS
  Our results suggest that the effect of LOV on viremia depends on the timing of treatment and on the number of doses administered. We observed a significant increase in the survival rate in both schemes due to a delay in the progression of the disease. However, the results obtained in the post-treatment scheme must be handled carefully because this treatment scheme increases viremia and we do not know how this increase could affect disease progression in humans.
authors.affiliation: Programa de Estudio y Control de Enfermedades Tropicales, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Marlen
authors.initials: M
authors.lastname: Martinez-Gutierrez
authors.affiliation: Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia ; Laboratorio de Patología, Congregación Mariana, Medellin, Colombia.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Correa-Londoño
authors.affiliation: Grupo de Virología, Universidad El Bosque, Bogotá, Colombia.
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Castellanos
authors.affiliation: Molecular and Translational Medicine Group, Viral Vector Core and Gene Therapy of the Neuroscience's Group of Antioquia, Universidad de Antioquia, Medellín, Colombia ; Molecular and Translational Medicine Group, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Gallego-Gómez
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Osorio
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003715:Dengue / Q000188:drug therapy*; D003716:Dengue Virus / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D053208:Kaplan-Meier Estimate; D008148:Lovastatin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008817:Mice, Mutant Strains; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy*; D019065:Virus Assembly / Q000187:drug effects
chemical_list: D008148:Lovastatin