title: Andes-virus-induced cytokine storm is partially suppressed by ribavirin.
abstract: BACKGROUND
  Microbe-induced over-activation of cytokines, especially tumour necrosis factor (TNF)-α, is key to the pathogenesis of hantavirus infection leading to severe inflammation with high mortality rate. Although ribavirin showed promise in inhibiting viral replication in vitro, its clinical efficacy remains controversial.
  
  
  METHODS
  Various concentrations of ribavirin were used to determine its effect on cytokine activation in our infectious model system.
  
  
  RESULTS
  Ribavirin decreased the virus load and dose-dependently inhibited the accumulation of RANTES messenger RNA in Andes-virus (ANDV)-infected human endothelial cells, but failed to suppress TNF-α-induced activation of RANTES and interleukin-6 in ANDV-inoculated cultures. This report also shows, for the first time, that the deleterious over-stimulation by TNF-α is mediated by nuclear factor-κB, and describes the effect of ribavirin on cytokine production following ANDV infection.
  
  
  CONCLUSIONS
  Although highly effective in preventing ANDV replication and suppressing activation of select inflammatory mediators, the therapeutic efficacy of ribavirin is limited due to its inability to fully inhibit cytokine outburst triggered by hantavirus infection.
authors.affiliation: Whittemor Peterson Institute, University of Nevada-Reno, Reno, NV, USA. sv.khaiboullina@gmail.com.
authors.forename: Svetlana F
authors.initials: SF
authors.lastname: Khaiboullina
authors.forename: Albert A
authors.initials: AA
authors.lastname: Rizvanov
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Lombardi
authors.forename: Sergey P
authors.initials: SP
authors.lastname: Morzunov
authors.forename: Helton J
authors.initials: HJ
authors.lastname: Reis
authors.forename: András
authors.initials: A
authors.lastname: Palotás
authors.forename: Stephen
authors.initials: S
authors.lastname: St Jeor
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D018946:Chemokine CCL5 / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006476:Orthohantavirus / Q000187:drug effects* / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D012254:Ribavirin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D014709:Vero Cells; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; C483024:CCL5 protein, human; D018946:Chemokine CCL5; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D012254:Ribavirin