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Non-permissive human conventional CD1c+ dendritic cells enable trans-infection of human primary renal tubular epithelial cells and protect BK polyomavirus from neutralization
The BK polyomavirus (BKPyV) is a ubiquitous human virus that persists in the renourinary epithelium. Immunosuppression can lead to BKPyV reactivation in the first year post-transplantation in kidney transplant recipients (KTRs) and hematopoietic stem cell transplant recipients. In KTRs, persistent D...
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Published in: | PLoS pathogens 2021-02, Vol.17 (2), p.e1009042-e1009042 |
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creator | Sikorski, Mathieu Coulon, Flora Peltier, Cécile Braudeau, Cécile Garcia, Alexandra Giraud, Matthieu Renaudin, Karine Kandel-Aznar, Christine Nedellec, Steven Hulin, Philippe Branchereau, Julien Véziers, Joëlle Gaboriaud, Pauline Touzé, Antoine Burlaud-Gaillard, Julien Josien, Régis McIlroy, Dorian Bressollette-Bodin, Céline Halary, Franck |
description | The BK polyomavirus (BKPyV) is a ubiquitous human virus that persists in the renourinary epithelium. Immunosuppression can lead to BKPyV reactivation in the first year post-transplantation in kidney transplant recipients (KTRs) and hematopoietic stem cell transplant recipients. In KTRs, persistent DNAemia has been correlated to the occurrence of polyomavirus-associated nephropathy (PVAN) that can lead to graft loss if not properly controlled. Based on recent observations that conventional dendritic cells (cDCs) specifically infiltrate PVAN lesions, we hypothesized that those cells could play a role in BKPyV infection. We first demonstrated that monocyte-derived dendritic cells (MDDCs), an in vitro model for mDCs, captured BKPyV particles through an unconventional GRAF-1 endocytic pathway. Neither BKPyV particles nor BKPyV-infected cells were shown to activate MDDCs. Endocytosed virions were efficiently transmitted to permissive cells and protected from the antibody-mediated neutralization. Finally, we demonstrated that freshly isolated CD1c+ mDCs from the blood and kidney parenchyma behaved similarly to MDDCs thus extending our results to cells of clinical relevance. This study sheds light on a potential unprecedented CD1c+ mDC involvement in the BKPyV infection as a promoter of viral spreading. |
doi_str_mv | 10.1371/JOURNAL.PPAT.1009042 |
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Immunosuppression can lead to BKPyV reactivation in the first year post-transplantation in kidney transplant recipients (KTRs) and hematopoietic stem cell transplant recipients. In KTRs, persistent DNAemia has been correlated to the occurrence of polyomavirus-associated nephropathy (PVAN) that can lead to graft loss if not properly controlled. Based on recent observations that conventional dendritic cells (cDCs) specifically infiltrate PVAN lesions, we hypothesized that those cells could play a role in BKPyV infection. We first demonstrated that monocyte-derived dendritic cells (MDDCs), an in vitro model for mDCs, captured BKPyV particles through an unconventional GRAF-1 endocytic pathway. Neither BKPyV particles nor BKPyV-infected cells were shown to activate MDDCs. Endocytosed virions were efficiently transmitted to permissive cells and protected from the antibody-mediated neutralization. Finally, we demonstrated that freshly isolated CD1c+ mDCs from the blood and kidney parenchyma behaved similarly to MDDCs thus extending our results to cells of clinical relevance. This study sheds light on a potential unprecedented CD1c+ mDC involvement in the BKPyV infection as a promoter of viral spreading.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/JOURNAL.PPAT.1009042</identifier><identifier>PMID: 33592065</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Biology and Life Sciences ; CD1c antigen ; Dendritic cells ; Endosomes ; Epithelial cells ; Epithelium ; Exo-a-sialidase ; Genotype & phenotype ; Genotypes ; Human health and pathology ; Infections ; Invaginations ; Life Sciences ; Medicine and Health Sciences ; Neutralization ; Research and Analysis Methods ; Statistical analysis ; Variance analysis ; Vesicles</subject><ispartof>PLoS pathogens, 2021-02, Vol.17 (2), p.e1009042-e1009042</ispartof><rights>2021 Sikorski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Immunosuppression can lead to BKPyV reactivation in the first year post-transplantation in kidney transplant recipients (KTRs) and hematopoietic stem cell transplant recipients. In KTRs, persistent DNAemia has been correlated to the occurrence of polyomavirus-associated nephropathy (PVAN) that can lead to graft loss if not properly controlled. Based on recent observations that conventional dendritic cells (cDCs) specifically infiltrate PVAN lesions, we hypothesized that those cells could play a role in BKPyV infection. We first demonstrated that monocyte-derived dendritic cells (MDDCs), an in vitro model for mDCs, captured BKPyV particles through an unconventional GRAF-1 endocytic pathway. Neither BKPyV particles nor BKPyV-infected cells were shown to activate MDDCs. Endocytosed virions were efficiently transmitted to permissive cells and protected from the antibody-mediated neutralization. Finally, we demonstrated that freshly isolated CD1c+ mDCs from the blood and kidney parenchyma behaved similarly to MDDCs thus extending our results to cells of clinical relevance. This study sheds light on a potential unprecedented CD1c+ mDC involvement in the BKPyV infection as a promoter of viral spreading.</description><subject>Acids</subject><subject>Biology and Life Sciences</subject><subject>CD1c antigen</subject><subject>Dendritic cells</subject><subject>Endosomes</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Exo-a-sialidase</subject><subject>Genotype & phenotype</subject><subject>Genotypes</subject><subject>Human health and pathology</subject><subject>Infections</subject><subject>Invaginations</subject><subject>Life Sciences</subject><subject>Medicine and Health Sciences</subject><subject>Neutralization</subject><subject>Research and Analysis Methods</subject><subject>Statistical analysis</subject><subject>Variance 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human conventional CD1c+ dendritic cells enable trans-infection of human primary renal tubular epithelial cells and protect BK polyomavirus from neutralization</title><author>Sikorski, Mathieu ; Coulon, Flora ; Peltier, Cécile ; Braudeau, Cécile ; Garcia, Alexandra ; Giraud, Matthieu ; Renaudin, Karine ; Kandel-Aznar, Christine ; Nedellec, Steven ; Hulin, Philippe ; Branchereau, Julien ; Véziers, Joëlle ; Gaboriaud, Pauline ; Touzé, Antoine ; Burlaud-Gaillard, Julien ; Josien, Régis ; McIlroy, Dorian ; Bressollette-Bodin, Céline ; Halary, Franck</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c560t-f468e209883782de8123d8f044f584ff5d2e76cbd2d30b1b1a6c6a4cf21d302b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acids</topic><topic>Biology and Life Sciences</topic><topic>CD1c antigen</topic><topic>Dendritic cells</topic><topic>Endosomes</topic><topic>Epithelial 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Pathog</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>17</volume><issue>2</issue><spage>e1009042</spage><epage>e1009042</epage><pages>e1009042-e1009042</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>The BK polyomavirus (BKPyV) is a ubiquitous human virus that persists in the renourinary epithelium. Immunosuppression can lead to BKPyV reactivation in the first year post-transplantation in kidney transplant recipients (KTRs) and hematopoietic stem cell transplant recipients. In KTRs, persistent DNAemia has been correlated to the occurrence of polyomavirus-associated nephropathy (PVAN) that can lead to graft loss if not properly controlled. Based on recent observations that conventional dendritic cells (cDCs) specifically infiltrate PVAN lesions, we hypothesized that those cells could play a role in BKPyV infection. We first demonstrated that monocyte-derived dendritic cells (MDDCs), an in vitro model for mDCs, captured BKPyV particles through an unconventional GRAF-1 endocytic pathway. Neither BKPyV particles nor BKPyV-infected cells were shown to activate MDDCs. Endocytosed virions were efficiently transmitted to permissive cells and protected from the antibody-mediated neutralization. Finally, we demonstrated that freshly isolated CD1c+ mDCs from the blood and kidney parenchyma behaved similarly to MDDCs thus extending our results to cells of clinical relevance. This study sheds light on a potential unprecedented CD1c+ mDC involvement in the BKPyV infection as a promoter of viral spreading.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33592065</pmid><doi>10.1371/JOURNAL.PPAT.1009042</doi><orcidid>https://orcid.org/0000-0002-3731-4017</orcidid><orcidid>https://orcid.org/0000-0003-0119-1905</orcidid><orcidid>https://orcid.org/0000-0003-0284-7363</orcidid><orcidid>https://orcid.org/0000-0003-1129-0798</orcidid><orcidid>https://orcid.org/0000-0003-0336-9615</orcidid><orcidid>https://orcid.org/0000-0001-5171-9873</orcidid><orcidid>https://orcid.org/0000-0001-6535-2515</orcidid><orcidid>https://orcid.org/0000-0002-8460-9352</orcidid><orcidid>https://orcid.org/0000-0002-9856-9945</orcidid><orcidid>https://orcid.org/0000-0001-7900-7413</orcidid><orcidid>https://orcid.org/0000-0001-6661-8047</orcidid><orcidid>https://orcid.org/0000-0002-3031-5199</orcidid><orcidid>https://orcid.org/0000-0001-5175-0790</orcidid><orcidid>https://orcid.org/0000-0002-1208-9677</orcidid><orcidid>https://orcid.org/0000-0002-9740-0785</orcidid><oa>free_for_read</oa></addata></record> |
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ispartof | PLoS pathogens, 2021-02, Vol.17 (2), p.e1009042-e1009042 |
issn | 1553-7374 1553-7366 1553-7374 |
language | eng |
recordid | cdi_plos_journals_2501883521 |
source | Access via ProQuest (Open Access); PubMed Central |
subjects | Acids Biology and Life Sciences CD1c antigen Dendritic cells Endosomes Epithelial cells Epithelium Exo-a-sialidase Genotype & phenotype Genotypes Human health and pathology Infections Invaginations Life Sciences Medicine and Health Sciences Neutralization Research and Analysis Methods Statistical analysis Variance analysis Vesicles |
title | Non-permissive human conventional CD1c+ dendritic cells enable trans-infection of human primary renal tubular epithelial cells and protect BK polyomavirus from neutralization |
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