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.
Kamau
Edwin
E
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Takhampunya
Ratree
R
Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC 20057, USA.
Li
Tao
T
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Kelly
Eileen
E
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Peachman
Kristina K
KK
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD 21910, USA.
Lynch
Julia A
JA
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Sun
Peifang
P
Viral and Rickettsial Diseases Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Palmer
Dupeh R
DR
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
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