Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis

J Infect Dis. 2014 May 1;209(9):1331-42. doi: 10.1093/infdis/jit504. Epub 2013 Sep 24.


Middle East respiratory syndrome coronavirus (MERS-CoV) infection caused severe pneumonia and multiorgan dysfunction and had a higher crude fatality rate (around 50% vs. 10%) than SARS coronavirus (SARS-CoV) infection. To understand the pathogenesis, we studied viral replication, cytokine/chemokine response, and antigen presentation in MERS-CoV-infected human monocyte-derived macrophages (MDMs) versus SARS-CoV-infected MDMs. Only MERS-CoV can replicate in MDMs. Both viruses were unable to significantly stimulate the expression of antiviral cytokines (interferon α [IFN-α] and IFN-β) but induced comparable levels of tumor necrosis factor α and interleukin 6. Notably, MERS-CoV induced significantly higher expression levels of interleukin 12, IFN-γ, and chemokines (IP-10/CXCL-10, MCP-1/CCL-2, MIP-1α/CCL-3, RANTES/CCL-5, and interleukin 8) than SARS-CoV. The expression of major histocompatibility complex class I and costimulatory molecules were significantly higher in MERS-CoV-infected MDMs than in SARS-CoV-infected cells. MERS-CoV replication was validated by immunostaining of infected MDMs and ex vivo lung tissue. We conclusively showed that MERS-CoV can establish a productive infection in human macrophages. The aberrant induction of inflammatory cytokines/chemokines could be important in the disease pathogenesis.

Keywords: MERS-CoV; SARS-CoV; cytokine and chemokine response; pathogenesis; viral replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Cell Survival / immunology
  • Cells, Cultured
  • Chlorocebus aethiops
  • Coronavirus / immunology
  • Coronavirus / pathogenicity
  • Coronavirus / physiology*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology*
  • Cytokines / biosynthesis
  • Cytokines / immunology*
  • Humans
  • Lung / virology
  • Macrophages / immunology
  • Macrophages / virology*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology*
  • Vero Cells
  • Virus Replication / physiology*


  • Cytokines