Dengue virus infection promotes translocation of high mobility group box 1 protein from the nucleus to the cytosol in dendritic cells, upregulates cytokine production and modulates virus replication.
High mobility group box 1 (HMGB1) protein functions in regulation of transcription, cellular activation and pro-inflammatory responses. However, the potential role of HMGB1 during viral infection has not been investigated. This study attempted to elucidate whether the HMGB1-mediated inflammatory response contributes to the pathogenesis of dengue virus (DENV) infection. Our data showed that HMGB1 was released at low DENV infection levels (m.o.i. of 1) under non-necrotic conditions by human dendritic cells (DCs). When DENV-infected DCs were co-cultured with autologous T cells, there was increased production of HMGB1 by both cell types. HMGB1 regulated tumour necrosis factor alpha, interleukin (IL)-6, IL-8 and alpha interferon secretion in DENV-infected DCs. Additionally, increased HMGB1 production was associated with reduced DENV replication titres in DCs. These results suggest that HMGB1 production influences DENV infection in susceptible hosts.
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Edwin
E
Kamau
Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC 20057, USA.
Ratree
R
Takhampunya
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Tao
T
Li
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Eileen
E
Kelly
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD 21910, USA.
Kristina K
KK
Peachman
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Julia A
JA
Lynch
Viral and Rickettsial Diseases Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Peifang
P
Sun
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Dupeh R
DR
Palmer
D002467:Cell Nucleus / Q000737:chemistry*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D003716:Dengue Virus / Q000276:immunology*; D024243:HMGB1 Protein / Q000276:immunology*; D006801:Humans; D021381:Protein Transport; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
D016207:Cytokines; D024243:HMGB1 Protein