Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis

J Infect Dis. 2017 Jul 15;216(2):162-171. doi: 10.1093/infdis/jix171.

Abstract

Background: Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity.

Methods: I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR.

Results: I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells.

Conclusions: The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study.

Keywords: Zika virus; cytokines; inflammation; kidney; podocyte; renal; transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / immunology
  • Fluorescent Antibody Technique
  • Humans
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / virology*
  • Mesangial Cells / virology*
  • Podocytes / virology*
  • Real-Time Polymerase Chain Reaction
  • Zika Virus / pathogenicity*
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / pathology

Substances

  • Cytokines