Tuesday September 25, 2012 09:45 - 10:15 @ Rhodes 7 

Sensing viral nucleic acids by the innate immune system in drosophila

Abstract:

Viral infection is a major threat for all living organisms, which have evolved efficient antiviral defence mechanisms. Innate immunity is the first-line host defence program, which operates in all animals to inhibit growth of microorganisms and increase host survival. Innate immunity is activated upon sensing conserved molecular patterns characteristic of non-self or markers of tissue damage/cellular stress (also known as danger signals). Viral infections are particularly challenging for the immune system because viruses replicate within cells, using molecules from the host.

Using the fruitfly Drosophila melanogaster as a model, we have shown that viral infection triggers both an inducible response, leading to the production of molecules countering viral replication or increasing survival of the host, and RNA interference. Whereas the former is shared with vertebrates, the second is not. Interestingly however, one common theme between antiviral innate immunity in vertebrates and invertebrates is the sensing of the presence of double-stranded RNA in infected cells. Furthermore, the pattern-recognition receptors sensing dsRNA in the cytosol in mammals (RIG-I-like receptors) and flies (Dicer-2) share an evolutionarily conserved DExD/H box helicase domain.

In order to understand how Dicer-2 accesses to viral replication complexes, we have performed a proteomic analysis to identify novel partners of this molecule. We have identified many proteins associating with Dicer-2 in unchallenged or infected cells, some previously known and some novel. Interestingly, several proteins were observed only in virus-infected cells, suggesting the assembly of specific complexes to counter viral infection. The functional characterization of these molecules is in progress.