Maria Carla SALEH
G5 Viruses and RNAi
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
 
Research area of the Unit
 
The Viruses and RNAi lab was established in 2008. The laboratory studies the mechanisms that mediate the RNAi-based antiviral response in insects. RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA (dsRNA). One of the functions of this pathway is the defense against parasitic nucleic acids: transposons and viruses. Previous results demonstrated that viral infections in Drosophila melanogaster are fought by an antiviral RNAi responseand that components of the endocytic pathway are required for dsRNA entry to initiate the RNAi response. Recently the lab has shown that infected insect cells spread a systemic silencing signal that elicits a protective RNAi-dependent immunity throughout the organism. We develop a comprehensive approach that tackles how this nucleic acid-based immunity works in insects to generate an anti-viral stage. A better understanding of the role of RNA silencing in insects during virus infection will allow the exploitation of this pathway for improvement of public health related problems such as arbovirus infection and disease.
 
Contribution to the programme
 
Important infectious diseases such as dengue, chikungunya, Lyme disease, and malaria are transmitted to humans by insect vectors.  One of the key factors that modulates whether an insect is competent or not to transmit a given pathogen is the innate immune response of the insect.  Understanding how the infection is controlled within the insect before crossover to the human host could generate crucial new strategies to disrupt pathogen transmission.  The Saleh lab proposes to study whether the RNAi-based immunity allows insects to function as vectors for arthropod-borne human diseases by controlling infection. The lab uses a combination of genomics, biochemistry and cell biology tools on the insect model Drosophila melanogaster to explore the interactions between pathogens and the insect immune response that operate by pathways involving small RNAs. This particular approach addresses basic questions on arthropod biology: does RNAi control viral infection in insects, does RNAi modulate virus-arthropod interactions, does RNAi restrict the host range of arboviruses and can the arthropod-RNAi response be used as a strategy to control these arboviruses.
 
References over the past 5 years
1.    Saleh, MC, Tassetto, M., van Rij, R.P., Goic, B., Gausson, V.,Berry, B., Jacquier, C., Antoniewski, C., and Andino, R. (2009). Antiviral immunity in Drosophila requires systemic RNA interference spread. Nature 458, 346-350.
2.    Mueller, S., Gausson, V., Vodovar, N., Deddouche, S., Troxler, L., Perot, J., Pfeffer, S., Hoffmann, J.A., Saleh, MC, and Imler, J.L. (2010). RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila. Proc Natl Acad Sci U S A 107, 19390-19395.
3.    Gausson, V, & Saleh, MC. (2011) Viral Small RNA Cloning and Sequencing.Methods Mol Biol. 721:107-122.
4.    Obadia, B., & Saleh, MC. (2011) dsRNA Uptake in Adult Drosophila. Methods Mol Biol. 721:253-263.
5.    Vodovar, N., Goic, B., Blanc, H., and Saleh, MC. (2011). In silico reconstruction of viral genomes from small RNAs improves virus-derived small interfering RNA profiling. J Virol 85, 11016-11021.
6.    Vodovar, N., Bronkhorst, A.W., van Cleef, K.W.R., Miesen, P., Blanc, H., van Rij, R.P., & Saleh, MC. (2012) Arbovirus-Derived piRNAs Exhibit a Ping-Pong Signature in Mosquito Cells. PLoS ONE 7(1): e30861.
7.    Vodovar, N., and Saleh, MC. (2012). Of Insects and Viruses: The Role of Small RNAs in Insect Defence. Advances in Insect Physiology 42, 1-36.