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  • 1
    Online Resource
    Online Resource
    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
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2259-2259
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2259-2259
    Abstract: 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
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-2259
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 2
    Online Resource
    Online Resource
    Mitophagy Enhances Oncolytic Measles Virus Replication by Mitigating DDX58/RIG-I-Like Receptor Signaling
    American Society for Microbiology ; 2014
    In:  Journal of Virology Vol. 88, No. 9 ( 2014-05), p. 5152-5164
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 88, No. 9 ( 2014-05), p. 5152-5164
    Abstract: The success of future clinical trials with oncolytic viruses depends on the identification and the control of mechanisms that modulate their therapeutic efficacy. In particular, little is known about the role of autophagy in infection by attenuated measles virus of the Edmonston strain (MV-Edm). We investigated the interaction between autophagy, innate immune response, and oncolytic activity of MV-Edm, since the antiviral immune response is a known factor limiting virotherapies. We report that MV-Edm exploits selective autophagy to mitigate the innate immune response mediated by DDX58/RIG-I like receptors (RLRs) in non-small cell lung cancer (NSCLC) cells. Both RNA interference (RNAi) and overexpression approaches demonstrate that autophagy enhances viral replication and inhibits the production of type I interferons regulated by RLRs. We show that MV-Edm unexpectedly triggers SQSTM1/p62-mediated mitophagy, resulting in decreased mitochondrion-tethered mitochondrial antiviral signaling protein (MAVS) and subsequently weakening the innate immune response. These results unveil a novel infectious strategy based on the usurpation of mitophagy leading to mitigation of the innate immune response. This finding provides a rationale to modulate autophagy in oncolytic virotherapy. IMPORTANCE In vitro studies, preclinical experiments in vivo , and clinical trials with humans all indicate that oncolytic viruses hold promise for cancer therapy. Measles virus of the Edmonston strain (MV-Edm), which is an attenuated virus derived from the common wild-type measles virus, is paradigmatic for therapeutic oncolytic viruses. MV-Edm replicates preferentially in and kills cancer cells. The efficiency of MV-Edm is limited by the immune response of the host against viruses. In our study, we revealed that MV-Edm usurps a homeostatic mechanism of intracellular degradation of mitochondria, coined mitophagy, to attenuate the innate immune response in cancer cells. This strategy might provide a replicative advantage for the virus against the development of antiviral immune responses by the host. These findings are important since they may not only indicate that inducers of autophagy could enhance the efficacy of oncolytic therapies but also provide clues for antiviral therapy by targeting SQSTM1/p62-mediated mitophagy.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.03851-13
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2014
    detail.hit.zdb_id: 1495529-5
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  • 3
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    Online Resource
    Mitophagy switches cell death from apoptosis to necrosis in NSCLC cells treated with oncolytic measles virus
    Impact Journals, LLC ; 2014
    In:  Oncotarget Vol. 5, No. 11 ( 2014-06-15), p. 3907-3918
    Details
    In: Oncotarget, Impact Journals, LLC, Vol. 5, No. 11 ( 2014-06-15), p. 3907-3918
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    URL: Article
    DOI: 10.18632/oncotarget.v5i11
    DOI: 10.18632/oncotarget.2028
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2014
    detail.hit.zdb_id: 2560162-3
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