PMID- 34484872 OWN - NLM STAT- MEDLINE DCOM- 20211015 LR - 20211015 IS - 2162-402X (Electronic) IS - 2162-4011 (Print) IS - 2162-4011 (Linking) VI - 10 IP - 1 DP - 2021 TI - Differential infection of murine and human dendritic cell subsets by oncolytic vesicular stomatitis virus variants. PG - 1959140 LID - 10.1080/2162402X.2021.1959140 [doi] LID - 1959140 AB - Oncolytic viruses (OVs) can eradicate tumor cells and elicit antitumor immunity. VSV-GP, a chimeric vesicular stomatitis virus (VSV) with the glycoprotein (GP) of the lymphocytic choriomeningitis virus, is a promising new OV candidate. However, the interaction of VSV-GP with host immune cells is not fully understood. Dendritic cells (DCs) are essential for inducing efficient antitumor immunity. Thus, we aimed to investigate the interaction of VSV-GP with different murine and human DCs subsets in direct comparison to the less cytopathic variant VSV-dM51-GP and wild type VSV. Immature murine bone marrow-derived DCs (BMDCs) were equally infected and killed by VSV and VSV-GP. Human monocyte-derived DCs (moDCs) were more permissive to VSV. Interestingly, VSV-dM51-GP induced maturation instead of killing in both BMDCs and moDCs as well as a pronounced release of pro-inflammatory cytokines. Importantly, matured BMDCs and moDCs were no longer susceptible to VSV-GP infection. Mouse splenic conventional DC type 1 (cDC1) could be infected ex vivo by VSV and VSV-GP to a higher extent than cDC2. Systemic infection of mice with VSV-GP and VSV-dM51-GP resulted in strong activation of cDCs despite low infection rates in spleen and tumor tissue. Human blood cDC1 were equally infected by VSV and VSV-GP, whereas cDC2 showed preferential infection with VSV. Our study demonstrated differential DC infection, activation, and cytokine production after the treatment with VSV and VSV-GP variants among species and subsets, which should be taken into account when investigating immunological mechanisms of oncolytic virotherapy in mouse models and human clinical trials. CI - (c) 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. FAU - Pipperger, Lisa AU - Pipperger L AUID- ORCID: 0000-0001-7150-3586 AD - Institute of Virology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Riepler, Lydia AU - Riepler L AD - Institute of Virology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Kimpel, Janine AU - Kimpel J AD - Institute of Virology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Siller, Anita AU - Siller A AD - Central Institute of Blood Transfusion and Immunology, University Hospital Innsbruck, Innsbruck, Austria. FAU - Stoitzner, Patrizia AU - Stoitzner P AUID- ORCID: 0000-0002-8488-6704 AD - Department of Dermatology, Venereology & Allergology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Banki, Zoltan AU - Banki Z AUID- ORCID: 0000-0002-3826-5800 AD - Institute of Virology, Medical University of Innsbruck, Innsbruck, Austria. FAU - von Laer, Dorothee AU - von Laer D AD - Institute of Virology, Medical University of Innsbruck, Innsbruck, Austria. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210831 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 SB - IM MH - Animals MH - Dendritic Cells MH - Humans MH - Mice MH - *Oncolytic Virotherapy MH - *Oncolytic Viruses/genetics MH - *Vesicular Stomatitis MH - Vesicular stomatitis Indiana virus/genetics PMC - PMC8409795 OTO - NOTNLM OT - Oncolytic viruses OT - dendritic cells OT - infection OT - vesicular stomatitis virus COIS- No potential conflicts of interest were disclosed. EDAT- 2021/09/07 06:00 MHDA- 2021/10/16 06:00 PMCR- 2021/08/31 CRDT- 2021/09/06 06:03 PHST- 2021/09/06 06:03 [entrez] PHST- 2021/09/07 06:00 [pubmed] PHST- 2021/10/16 06:00 [medline] PHST- 2021/08/31 00:00 [pmc-release] AID - 1959140 [pii] AID - 10.1080/2162402X.2021.1959140 [doi] PST - epublish SO - Oncoimmunology. 2021 Aug 31;10(1):1959140. doi: 10.1080/2162402X.2021.1959140. eCollection 2021.