Gene expression analysis during dengue virus infection in HepG2 cells reveals virus control of innate immune response.

OBJECTIVES: Liver damage occurs during Dengue Virus infection and constitutes a characteristic of severe forms of the disease. The present study was focused on the modulation of gene expression in a human hepatic cell lineage, HepG2, in response to Dengue Virus infection. METHODS: The global gene expression changes in HepG2 cells after 6, 24 and 48h of infection with Dengue Virus were investigated using a new tool of microarray data analysis and real-time PCR. RESULTS: HepG2 cells infected with Dengue Virus showed alterations in several signaling pathways involved in innate immune response. The analysis of pattern recognition pathways genes demonstrated that TLR3, TLR8, RIG-I and MDA5 mRNAs were up-regulated during Dengue Virus infection along with an increase in the expression of the type I interferon, IFN-beta and pro-inflammatory cytokines IL-6, IL-8 and RANTES genes. CONCLUSIONS: Our results suggest that innate immune pathways are involved in the recognition of Dengue Virus by HepG2 cells. These observations may contribute to the understanding of the inflammatory responses induced by Dengue Virus-hepatocytes interaction during dengue diseases.