UMMS Affiliation

Center for Infectious Disease and Vaccine Research

Date

3-27-2001

Document Type

Article

Subjects

Antibodies, Viral; Biological Markers; Cell Differentiation; Cells, Cultured; Dendritic Cells; Dengue Virus; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Interferon Type II; Interferon-alpha; Interleukin-10; Interleukin-12; Myeloid Cells; Neutralization Tests; Tumor Necrosis Factor-alpha; Virus Replication

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The ability of dendritic cells (DCs) to shape the adaptive immune response to viral infection is mediated largely by their maturation and activation state as determined by the surface expression of HLA molecules, costimulatory molecules, and cytokine production. Dengue is an emerging arboviral disease where the severity of illness is influenced by the adaptive immune response to the virus. In this report, we have demonstrated that dengue virus infects and replicates in immature human myeloid DCs. Exposure to live dengue virus led to maturation and activation of both the infected and surrounding, uninfected DCs and stimulated production of tumor necrosis factor alpha (TNF-alpha) and alpha interferon (IFN-alpha). Activation of the dengue virus-infected DCs was blunted compared to the surrounding, uninfected DCs, and dengue virus infection induced low-level release of interleukin-12 p70 (IL-12 p70), a key cytokine in the development of cell-mediated immunity (CMI). Upon the addition of IFN-gamma, there was enhanced activation of dengue virus-infected DCs and enhanced dengue virus-induced IL-12 p70 release. The data suggest a model whereby DCs are the early, primary target of dengue virus in natural infection and the vigor of CMI is modulated by the relative presence or absence of IFN-gamma in the microenvironment surrounding the virus-infected DCs. These findings are relevant to understanding the pathogenesis of dengue hemorrhagic fever and the design of new vaccination and therapeutic strategies.

Rights and Permissions

Citation: J Virol. 2001 Apr;75(8):3501-8. Link to article on publisher's site

DOI of Published Version

10.1128/JVI.75.8.3501-3508.2001

Related Resources

Link to Article in PubMed

Journal Title

Journal of virology

PubMed ID

11264339

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