Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways

J Infect Dis. 2016 Mar 15;213(6):904-14. doi: 10.1093/infdis/jiv380. Epub 2015 Jul 22.

Abstract

Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV-infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.

Keywords: MERS-CoV; T lymphocytes; apoptosis; caspase; marmosets; spleen; tonsil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • Apoptosis / physiology*
  • Callithrix
  • Cells, Cultured
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism
  • Gene Expression Regulation
  • Humans
  • Middle East Respiratory Syndrome Coronavirus / physiology*
  • Palatine Tonsil / cytology
  • SARS Virus / physiology
  • Spleen / cytology
  • T-Lymphocytes / physiology
  • T-Lymphocytes / virology*

Substances

  • Antibodies, Viral
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4