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About the Authors:
Anon Srikiatkhachorn
* E-mail: [email protected]
Affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
Sineewanlaya Wichit
Affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
Robert V. Gibbons
Affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
Sharone Green
Affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
Daniel H. Libraty
Affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
Timothy P. Endy
Affiliation: Department of Medicine, State University of New York, Upstate Medical University, Syracuse, New York, United States of America
Francis A. Ennis
Affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
Siripen Kalayanarooj
Affiliation: Queen Sirikit National Institute of Child Health, Bangkok, Thailand
Alan L. Rothman
Affiliation: Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island, United States of America
Introduction
Infection with dengue viruses (DENV) causes a wide range of manifestations from asymptomatic infection to a febrile illness called dengue fever (DF), to dengue hemorrhagic fever (DHF), a viral hemorrhagic disease characterized by plasma leakage and bleeding diathesis. [1] The mechanisms of severe dengue disease are not completely elucidated. Both higher viral burden and enhanced immune activation have been associated with severity. [2] An important risk factor is a secondary DENV infection in a host previously infected with DENV of another serotype. Cross-reactive, non-neutralizing DENV-specific antibodies have been shown to enhance viral attachment and uptake by immunoglobulin receptor-bearing target cells, which may lead to higher viral loads and more intense immune activation. [3], [4]
The in vivo cellular targets of DENV remain to be completely identified. Studies of human dengue cases have identified macrophages and lymphoid cells as major targets of DENV as supported by the presence of viral antigen and RNA. [5]–[9] However, the relation of viral burden in various cell populations to clinical severity and host immunological status has not been examined. We measured DENV RNA in major cellular constituents of peripheral blood mononuclear cells (PBMC) in dengue cases and identified B cells as the principal cells harboring DENV in both DF and DHF cases. Secondary infection and DHF were associated...