Non-permissive human conventional CD1c+ dendritic cells enable trans-infection of human primary renal tubular epithelial cells and protect BK polyomavirus from neutralization.

• Main Authors: Mathieu Sikorski, Flora Coulon, Cécile Peltier, Cécile Braudeau, Alexandra Garcia, Matthieu Giraud, Karine Renaudin, Christine Kandel-Aznar, Steven Nedellec, Philippe Hulin, Julien Branchereau, Joëlle Véziers, Pauline Gaboriaud, Antoine Touzé, Julien Burlaud-Gaillard, Régis Josien, Dorian McIlroy, Céline Bressollette-Bodin, Franck Halary
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2021-02-01
• Series: PLoS Pathogens
• Online Access: https://doi.org/10.1371/journal.ppat.1009042

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.