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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
Main Authors: 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
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cited_by cdi_FETCH-LOGICAL-c560t-f468e209883782de8123d8f044f584ff5d2e76cbd2d30b1b1a6c6a4cf21d302b3
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container_issue 2
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container_title PLoS pathogens
container_volume 17
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. 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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.</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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identifier ISSN: 1553-7374
ispartof PLoS pathogens, 2021-02, Vol.17 (2), p.e1009042-e1009042
issn 1553-7374
1553-7366
1553-7374
language eng
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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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