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Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium.

Abstract

Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit.

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  • Authors+Show Affiliations

    ,

    Institute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.

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    Department for Biotechnology and Biophysics, University of Wuerzburg, Wuerzburg, Germany.

    ,

    Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.

    ,

    Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany. Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.

    ,

    Institute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.

    ,

    Fraunhofer Institute for Silicate Research ISC, Chair of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, University of Wuerzburg, Wuerzburg, Germany.

    ,

    Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.

    ,

    Department for Biotechnology and Biophysics, University of Wuerzburg, Wuerzburg, Germany.

    ,

    Institute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.

    Institute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.

    Source

    Frontiers in immunology 10: 2019 pg 1294

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31231395

    Citation

    Derakhshani, Shaghayegh, et al. "Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium." Frontiers in Immunology, vol. 10, 2019, p. 1294.
    Derakhshani S, Kurz A, Japtok L, et al. Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium. Front Immunol. 2019;10:1294.
    Derakhshani, S., Kurz, A., Japtok, L., Schumacher, F., Pilgram, L., Steinke, M., ... Avota, E. (2019). Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium. Frontiers in Immunology, 10, p. 1294. doi:10.3389/fimmu.2019.01294.
    Derakhshani S, et al. Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium. Front Immunol. 2019;10:1294. PubMed PMID: 31231395.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium. AU - Derakhshani,Shaghayegh, AU - Kurz,Andreas, AU - Japtok,Lukasz, AU - Schumacher,Fabian, AU - Pilgram,Lisa, AU - Steinke,Maria, AU - Kleuser,Burkhard, AU - Sauer,Markus, AU - Schneider-Schaulies,Sibylle, AU - Avota,Elita, Y1 - 2019/06/05/ PY - 2019/02/23/received PY - 2019/05/21/accepted PY - 2019/6/25/entrez PY - 2019/6/25/pubmed PY - 2019/6/25/medline KW - 3D tissue model KW - cell migration KW - dendritic cell KW - measles virus KW - sphingosine-1-phosphate SP - 1294 EP - 1294 JF - Frontiers in immunology JO - Front Immunol VL - 10 N2 - Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/31231395/Measles_Virus_Infection_Fosters_Dendritic_Cell_Motility_in_a_3D_Environment_to_Enhance_Transmission_to_Target_Cells_in_the_Respiratory_Epithelium L2 - https://dx.doi.org/10.3389/fimmu.2019.01294 DB - PRIME DP - Unbound Medicine ER -