{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:07:32Z","timestamp":1790784452286,"version":"4.1.0"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | NIH | National Cancer Institute","award":["1R15CA238864-01"],"award-info":[{"award-number":["1R15CA238864-01"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2023,9,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Oncolytic virus (OV) therapy is a promising virus-based approach against various malignancies, including pancreatic ductal adenocarcinoma (PDAC). Our previous studies demonstrated that human PDAC cell lines are highly variable in their permissiveness to OVs. Mouse PDAC cell lines, which are widely used for\n            <jats:italic>in vivo<\/jats:italic>\n            examination of the adaptive immune responses during OV and other cancer therapies, have never been examined systematically for the impact of intertumoral heterogeneity (the differences observed between tumors in different patients) on OV virus efficacy. Here, we examined phenotypically and genotypically three commonly used allograftable mouse PDAC cell lines (C57BL6 genetic background): Panc02 (derived from chemically induced PDAC; also known as Pan02), and two cell lines originated from PDACs developed in two different KPC (Kras\n            <jats:sup>G12D<\/jats:sup>\n            , Trp53\n            <jats:sup>R172H<\/jats:sup>\n            , and PDX-1-Cre) mouse models. Our study (i) characterized the ability of a widely used attenuated oncolytic vesicular stomatitis virus VSV-\u0394M51-GFP to infect, replicate in, and kill mouse PDAC cells; (ii) examined their innate antiviral responses; (iii) compared their permissiveness to a non-attenuated VSV-Mwt-GFP and chemotherapeutic drugs; and (iv) analyzed their karyotype and exome. Mouse PDAC cell lines showed high divergence in their permissiveness to VSV-\u0394M51-GFP, which negatively correlated with their abilities to mount innate antiviral responses, while all three cell lines were highly permissive to VSV-Mwt-GFP. No correlation was found between resistance to VSV-\u0394M51-GFP and chemotherapy. Also, mouse PDAC cell lines showed high divergence in their karyotype and exome. The exome analysis demonstrated that more VSV-\u0394M51-GFP-permissive mouse PDAC cell lines harbor mutations in multiple important antiviral genes, such as TYK2, JAK2, and JAK3.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Oncolytic virus (OV) therapy is a promising virus-based approach against various malignancies, including pancreatic ductal adenocarcinoma (PDAC). Our previous studies using various human PDAC cell lines demonstrated that they are highly variable in their permissiveness to OVs. In this study, we examined phenotypically and genotypically three commonly used allograftable mouse PDAC cell lines, which are widely used for\n              <jats:italic>in vivo<\/jats:italic>\n              examination of the adaptive immune responses during cancer therapies. Mouse PDAC cell lines showed high divergence in their permissiveness to oncolytic vesicular stomatitis virus (VSV), which negatively correlated with their abilities to mount innate antiviral responses. Also, we discovered that more VSV-permissive mouse PDAC cell lines harbor mutations in multiple important antiviral genes, such as TYK2, JAK2, and JAK3. Our study provides essential information about three model mouse PDAC cell lines and proposes a novel platform to study OV-based therapies against different PDACs in immunocompetent mice.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01005-23","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T13:02:47Z","timestamp":1694005367000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Intertumoral heterogeneity impacts oncolytic vesicular stomatitis virus efficacy in mouse pancreatic cancer cells"],"prefix":"10.1128","volume":"97","author":[{"given":"Dakota W.","family":"Goad","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte , Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Y.","family":"Nesmelova","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte , Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel R.","family":"Yohe","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Genomics, University of North Carolina at Charlotte , Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8715-3840","authenticated-orcid":false,"given":"Valery Z.","family":"Grdzelishvili","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte , Charlotte, North Carolina, USA"},{"name":"School of Data Science, University of North Carolina at Charlotte , Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30974-0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00719-w"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9794-7_1"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000980"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10091092"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.046672-0"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2013.06.003"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1214441110"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/77558"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2004.03.003"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25088"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2022.13355"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13051171"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.21037\/apc.2020.03.03"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.37529"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.670"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11202"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.11.014"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05640-11"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.04.023"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-2050"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24580"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080580"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02040-09"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00211-06"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.034793"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-14-0214"},{"key":"e_1_3_4_30_2","first-page":"717","article-title":"Induction and chemotherapeutic response of two transplantable ductal adenocarcinomas of the pancreas in C57Bl\/6 mice","volume":"44","author":"Corbett TH","year":"1984","unstructured":"Corbett TH , Roberts BJ , Leopold WR , Peckham JC , Wilkoff LJ , Griswold DP , Schabel FM . 1984. 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