West Nile virus sfRNA prevents incorporation of anti-viral molecules into exosomes to facilitate virus spread — ASN Events
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  3. West Nile virus sfRNA prevents incorporation of anti-viral molecules into exosomes to facilitate virus spread

West Nile virus sfRNA prevents incorporation of anti-viral molecules into exosomes to facilitate virus spread (#234)

Brian D Clarke 1 , Jeff Wilusz 2 , Alexander A Khromykh 1
  1. Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia
  2. Department of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, CO, USA

Exosomes and microvesicles are small 40 - 100 nm extracellular vesicles, which act as carriers for intercellular signalling. In particular, these vesicles are packed with small RNAs, such as microRNAs, as well as proteins, and mRNAs. In this study, we show that microvesicles derived from A549 cells stimulated with interferon (IFN) are potent inhibitors of West Nile virus (WNV) replication in cells treated with these extracellular vesicles. siRNA knockdown of cellular RNases Xrn1, Dicer, Drosha, and RNaseL in IFN-stimulated cells reduced the anti-WNV activity of extracellular vesicles.  Anti-WNV activity was also observed for vesicles derived from cells infected with WNV mutant IRAΔCS3 deficient in generation of subgeneric flavivirus RNA (sfRNA) but not for vesicles derived from wild type WNV-infected cells. We have previously shown that WNV sfRNA inhibits cellular RNA decay pathway by inactivating Xrn1 and RNAi pathway by inhibiting Dicer. Therefore, we propose that WNV sfRNA inhibits generation of anti-viral RNA decay intermediates and/or miRNAs and their subsequent incorporation into microvesicles and exosomes in order to facilitate virus spread. To test the hypothesis we are undertaking RNAseq to identify exosomal RNAs from WT and IRAΔCS3 infected cells and will present the data at the meeting.