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Heart and skeletal muscle are targets of dengue virus infection.

ABSTRACT: 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.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.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.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.

SUBMITTER: Salgado DM

PROVIDER: S-EPMC2833338 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Heart and skeletal muscle are targets of dengue virus infection.

Salgado Doris Martha DM Eltit José Miguel JM Mansfield Keith K Panqueba César C Castro Dolly D Vega Martha Rocio MR Xhaja Kris K Schmidt Diane D Martin Katherine J KJ Allen Paul D PD Rodriguez Jairo Antonio JA Dinsmore Jonathan H JH López José Rafael JR Bosch Irene I

The Pediatric infectious disease journal 20100301 3

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 20032806

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Project description:Chikungunya virus (CHIKV) is an arthritogenic alphavirus that acutely causes fever as well as severe joint and muscle pain. Chronic musculoskeletal pain persists in a substantial fraction of patients for months to years after the initial infection, yet we still have a poor understanding of what promotes chronic disease. While replicating virus has not been detected in joint-associated tissues of patients with persistent arthritis nor in various animal models at convalescent time points, viral RNA is detected months after acute infection. To identify the cells that might contribute to pathogenesis during this chronic phase, we developed a recombinant CHIKV that expresses Cre recombinase (CHIKV-3'-Cre). CHIKV-3'-Cre replicated in myoblasts and fibroblasts, and it induced arthritis during the acute phase in mice. Importantly, it also induced chronic disease, including persistent viral RNA and chronic myositis and synovitis similar to wild-type virus. CHIKV-3'-Cre infection of tdTomato reporter mice resulted in a population of tdTomato+ cells that persisted for at least 112 days. Immunofluorescence and flow cytometric profiling revealed that these tdTomato+ cells predominantly were myofibers and dermal and muscle fibroblasts. Treatment with an antibody against Mxra8, a recently defined host receptor for CHIKV, reduced the number of tdTomato+ cells in the chronic phase and diminished the levels of chronic viral RNA, implicating these tdTomato+ cells as the reservoir of chronic viral RNA. Finally, isolation and flow cytometry-based sorting of the tdTomato+ fibroblasts from the skin and ankle and analysis for viral RNA revealed that the tdTomato+ cells harbor most of the persistent CHIKV RNA at chronic time points. Therefore, this CHIKV-3'-Cre and tdTomato reporter mouse system identifies the cells that survive CHIKV infection in vivo and are enriched for persistent CHIKV RNA. This model represents a useful tool for studying CHIKV pathogenesis in the acute and chronic stages of disease.

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Heart and skeletal muscle are targets of dengue virus infection.

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Heart and skeletal muscle are targets of dengue virus infection.

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