PT - JOURNAL ARTICLE AU - Mathieu Sikorski AU - Flora Coulon AU - Cécile Peltier AU - Cécile Braudeau AU - Alexandra Garcia AU - Matthieu Giraud AU - Karine Renaudin AU - Christine Kandel-Aznar AU - Steven Nedellec AU - Philipe Hulin AU - Julien Branchereau AU - Joëlle Véziers AU - Pauline Gaboriaud AU - Antoine Touzé AU - Julien Burlaud-Gaillard AU - Régis Josien AU - Dorian McIlroy AU - Céline Bressollette-Bodin AU - Franck Halary TI - Non-permissive human conventional CD1c<sup>+</sup> dendritic cells enable <em>trans</em>-infection of human primary renal tubular epithelial cells and protect BK polyomavirus from neutralization AID - 10.1101/2020.09.04.282426 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.09.04.282426 4099 - http://biorxiv.org/content/early/2020/09/04/2020.09.04.282426.short 4100 - http://biorxiv.org/content/early/2020/09/04/2020.09.04.282426.full AB - 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 (KTR) and hematopoietic stem cell transplant recipients. In KTR, 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 (cDC) specifically infiltrate PVAN lesions, we hypothesized that those cells could play a role in BKPyV infection. We first demonstrated that monocyte-derived DC (MDDC), an in vitro model for mDC, captured BKPyV particles through an unconventional GRAF-1 endocytic pathway. Neither BKPyV particles nor BKPyV-infected cells were shown to activate MDDC. Endocytosed virions were efficiently transmitted to permissive cells and shown to be protected from the antibody-mediated neutralization. Finally, we demonstrated that freshly isolated CD1c+ mDC from the blood and kidney parenchyma behaved similarly to MDDC 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.Competing Interest StatementThe authors have declared no competing interest.