Novel innate immunity and antiviral responses are revealed in primary human muscle cells infected with dengue virus

CYBELE C. GARCÍA

Foz do Iguazu

Congreso; 26 Congresso Brasileiro de Microbiologia; 2011

The identification of antiviral response signature genes and the discovery of crucial virus-host interactions will lead to a better understanding of the molecular mechanisms underlying viral pathogenesis. It contributes to the advancement of disease prognosis assessment and therapeutic innovation. The cellular factors that mediate defenses against viruses are complex and include products of interferon type I and II stimulation; stimulation of pathogen recognition receptors and their signaling; biochemical protein modifications such as ISGylation and ubiquitination; increased metabolic output, miRNA regulation and other cellular responses like apoptosis and growth regulation. To begin studying the overall cell and tissue response to viruses, we employed mRNA profiling of infected human primary cells. Among the differentially expressed genes analyzed there were some that were discovered to be responsible, alone or in combination, for halting virus spread. But great majority of the gene expression response remains unexplored until now. We designed reverse genetic strategies as an approach to test antiviral activity and for functional identification of cell-specific antiviral proteins. The shRNA screen consisted of 75 genes selected for the un-bias gene expression analysis for which 5 independent hairpins were designed. The high-throughput screen was facilitated by the use of novel luciferase-expressing dengue virus, providing a rapid and effective way to define host factors that impact the production of viral progeny. The cell system utilized consisted of primary human myoblasts cells that are able to sustain a robust innate immunity response to dengue virus and are relevant physiological targets in vivo. The results presented in this meeting provide unique information regarding dengue virus control and possible novel therapeutic mechanisms for elimination of pathogenic viruses in the human body.