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

PLoS Pathog. 2021 Feb 16;17(2):e1009042. doi: 10.1371/journal.ppat.1009042. eCollection 2021 Feb.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antigens, CD1 / metabolism*
  • BK Virus / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Glycoproteins / metabolism*
  • Humans
  • Kidney / immunology*
  • Kidney / metabolism
  • Kidney / virology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / virology
  • Polyomavirus Infections / immunology*
  • Polyomavirus Infections / metabolism
  • Polyomavirus Infections / virology
  • Tumor Virus Infections / immunology*
  • Tumor Virus Infections / metabolism
  • Tumor Virus Infections / virology
  • Virus Replication

Substances

  • Antibodies, Neutralizing
  • Antigens, CD1
  • CD1C protein, human
  • Glycoproteins

Grant support

This work received financial supports from the Fondation d’Entreprises Progreffe to MS (no grant number available; https://www.progreffe.com) and from the IHU-Cesti project to FH (grant number: ANR-10-IBHU-005; https://anr.fr/en/funded-projects-and-impact/funded-projects/project/funded/invest/09c1e0aff260d3fe864f14a372a3ab61/?tx_anrprojects_funded%5Bcontroller%5D=Funded&cHash=804a79048d8d5ef578e84fdef7aec94a). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.