GSBS Student Publications

Title

TRAIL is a novel antiviral protein against dengue virus

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Center for Infectious Disease and Vaccine Research; Department of Medicine, Division of Infectious Diseases and Immunology

Date

10-5-2007

Document Type

Article

Medical Subject Headings

B-Lymphocytes; Cell Line; Cells, Cultured; Dendritic Cells; Dengue Virus; Endothelial Cells; Gene Expression Profiling; Humans; Monocytes; Oligonucleotide Array Sequence Analysis; RNA, Messenger; TNF-Related Apoptosis-Inducing Ligand

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Dengue fever is an important tropical illness for which there is currently no virus-specific treatment. To shed light on mechanisms involved in the cellular response to dengue virus (DV), we assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of infected primary human cells and identified changes common to all cells. The common response genes included a set of 23 genes significantly induced upon DV infection of human umbilical vein endothelial cells (HUVECs), dendritic cells (DCs), monocytes, and B cells (analysis of variance, P < 0.05). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), one of the common response genes, was identified as a key link between type I and type II interferon response genes. We found that DV induces TRAIL expression in immune cells and HUVECs at the mRNA and protein levels. The induction of TRAIL expression by DV was found to be dependent on an intact type I interferon signaling pathway. A significant increase in DV RNA accumulation was observed in anti-TRAIL antibody-treated monocytes, B cells, and HUVECs, and, conversely, a decrease in DV RNA was seen in recombinant TRAIL-treated monocytes. Furthermore, recombinant TRAIL inhibited DV titers in DV-infected DCs by an apoptosis-independent mechanism. These data suggest that TRAIL plays an important role in the antiviral response to DV infection and is a candidate for antiviral interventions against DV.

Rights and Permissions

Citation: J Virol. 2008 Jan;82(1):555-64. Epub 2007 Oct 3. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Journal of virology

PubMed ID

17913827