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. 2021 Aug 31;10(1):1959140.
doi: 10.1080/2162402X.2021.1959140. eCollection 2021.

Differential infection of murine and human dendritic cell subsets by oncolytic vesicular stomatitis virus variants

Lisa Pipperger  1 , Lydia Riepler  1 , Janine Kimpel  1 , Anita Siller  2 , Patrizia Stoitzner  3 , Zoltán Bánki  1 , Dorothee von Laer  1
Affiliations

Differential infection of murine and human dendritic cell subsets by oncolytic vesicular stomatitis virus variants

Lisa Pipperger et al. Oncoimmunology. .

Abstract

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.

Keywords: Oncolytic viruses; dendritic cells; infection; vesicular stomatitis virus.

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Conflict of interest statement

No potential conflicts of interest were disclosed.

Figures

Figure 1.
Figure 1.
Infection of mouse BMDCs with VSV, VSV-GP, and VSV-dM51-GP
Figure 2.
Figure 2.
VSV-GP infects and kills immature BMDCs while VSV-dM51-GP leads to maturation of BMDC cultures
Figure 3.
Figure 3.
VSV-GP variants and VSV infect splenic conventional DCs ex vivo
Figure 4.
Figure 4.
Infection of splenic DCs and tumor-associated DC is low in vivo but VSV-GP and VSV-dM51-GP activated the DC subsets
Figure 5.
Figure 5.
VSV-GP variants infect human monocyte-derived immature DCs less than VSV
Figure 6.
Figure 6.
Human blood conventional DCs can be infected by VSV-GP variants and VSV while plasmacytoid DCs are resistant to infection
Figure 7.
Figure 7.
Different cytokine profiles are induced in murine and human DCs in response to VSV variants
See this image and copyright information in PMC

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