title: Heart and skeletal muscle are targets of dengue virus infection.
abstract: BACKGROUND
  Dengue fever is one of the most significant re-emerging tropical diseases, despite our expanding knowledge of the disease, viral tropism is still not known to target heart tissues or muscle.
  
  
  METHODS
  A prospective pediatric clinical cohort of 102 dengue hemorrhagic fever patients from Colombia, South America, was followed for 1 year. Clinical diagnosis of myocarditis was routinely performed. Electrocardiograph and echocardiograph analysis were performed to confirm those cases. Immunohistochemistry for detection of dengue virus and inflammatory markers was performed on autopsied heart tissue. In vitro studies of human striated skeletal fibers (myotubes) infected with dengue virus were used as a model for myocyte infection. Measurements of intracellular Ca2+ concentration as well as immunodetection of dengue virus and inflammation markers in infected myotubes were performed.
  
  
  RESULTS
  Eleven children with dengue hemorrhagic fever presented with symptoms of myocarditis. Widespread viral infection of the heart, myocardial endothelium, and cardiomyocytes, accompanied by inflammation was observed in 1 fatal case. Immunofluorescence confocal microscopy showed that myotubes were infected by dengue virus and had increased expression of the inflammatory genes and protein IP-10. The infected myotubes also had increases in intracellular Ca2+ concentration.
  
  
  CONCLUSIONS
  Vigorous infection of heart tissues in vivo and striated skeletal cells in vitro are demonstrated. Derangements of Ca2+ storage in the infected cells may directly contribute to the presentation of myocarditis in pediatric patients.
authors.affiliation: Universidad Surcolombiana and Pediatric Unit, Hospital Universitario de Neiva, Neiva, Colombia.
authors.forename: Doris Martha
authors.initials: DM
authors.lastname: Salgado
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Eltit
authors.forename: Keith
authors.initials: K
authors.lastname: Mansfield
authors.forename: César
authors.initials: C
authors.lastname: Panqueba
authors.forename: Dolly
authors.initials: D
authors.lastname: Castro
authors.forename: Martha Rocio
authors.initials: MR
authors.lastname: Vega
authors.forename: Kris
authors.initials: K
authors.lastname: Xhaja
authors.forename: Diane
authors.initials: D
authors.lastname: Schmidt
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Martin
authors.forename: Paul D
authors.initials: PD
authors.lastname: Allen
authors.forename: Jairo Antonio
authors.initials: JA
authors.lastname: Rodriguez
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Dinsmore
authors.forename: José Rafael
authors.initials: JR
authors.lastname: López
authors.forename: Irene
authors.initials: I
authors.lastname: Bosch
mesh_terms: D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003105:Colombia; D003600:Cytosol / Q000737:chemistry; D003716:Dengue Virus / Q000472:pathogenicity / Q000502:physiology*; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008853:Microscopy; D018482:Muscle, Skeletal / Q000473:pathology / Q000821:virology*; D009206:Myocardium / Q000473:pathology; D011446:Prospective Studies; D019595:Severe Dengue / Q000473:pathology*; D056189:Viral Tropism
chemical_list: D018836:Inflammation Mediators; D002118:Calcium