Abstract 2259: Oncolytic attenuated measles virus exploits autophagy for its replication and spreads by suppressing Rig-1 like receptors (RLRs) in non-small cell lung cancer cells

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Both autophagy and RLRs are involved in response to microbial infection, including oncolytic attenuated measles viruses, which are being tested in several clinical trials in advanced cancer patients. As little is known about the role of autophagy in measles virus infection and oncolytic activity as well as the crosstalk with RLRs, these mechanisms require further investigation. In this study, we show for the first time that measles virus of the Edmonston strain (MV-Edm) exploits autophagy for its replication and spreads by suppressing RLRs in non-small cell lung cancer cells (NSCLCs). MV-Edm rapidly induced autophagosomes formation in NSCLCs. Inhibition of autophagy by RNAi led to a hampered viral replication/spread accompanied by robustly increased production of type-I interferons. Conversely, overexpression of autophagic genes massively reduced production of type-I interferons and enhanced viral replication. Expression of RIG-I and MDA5 was enhanced in MV-Edm infected NSCLCs and massively increased when autophagy was concomitantly inhibited, suggesting that virus-induced autophagy participated in modulating RLR-mediated anti-viral response. As enhancing viral replication and spread within tumors could improve oncolytic efficiency, our work may lead to improve clinical therapeutic efficacy of oncolytic MV-Edm when combined with autophagy inducers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2259. doi:1538-7445.AM2012-2259