TY - JOUR
T1 - Heart and skeletal muscle are targets of dengue virus infection
AU - Salgado, Doris Martha
AU - Eltit, José Miguel
AU - Mansfield, Keith
AU - Panqueba, César
AU - Castro, Dolly
AU - Vega, Martha Rocio
AU - Xhaja, Kris
AU - Schmidt, Diane
AU - Martin, Katherine J.
AU - Allen, Paul D.
AU - Rodriguez, Jairo Antonio
AU - Dinsmore, Jonathan H.
AU - López, José Rafael
AU - Bosch, Irene
PY - 2010/3
Y1 - 2010/3
N2 - 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 Ca 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 Ca concentration. Conclusions: Vigorous infection of heart tissues in vivo and striated skeletal cells in vitro are demonstrated. Derangements of Ca storage in the infected cells may directly contribute to the presentation of myocarditis in pediatric patients.
AB - 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 Ca 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 Ca concentration. Conclusions: Vigorous infection of heart tissues in vivo and striated skeletal cells in vitro are demonstrated. Derangements of Ca storage in the infected cells may directly contribute to the presentation of myocarditis in pediatric patients.
KW - Calcium transport
KW - Dengue
KW - Inflammation
KW - Myocarditis
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U2 - 10.1097/INF.0b013e3181bc3c5b
DO - 10.1097/INF.0b013e3181bc3c5b
M3 - Article
C2 - 20032806
AN - SCOPUS:77649201177
VL - 29
SP - 238
EP - 242
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
SN - 0891-3668
IS - 3
ER -