Productive replication of Middle East respiratory syndrome coronavirus in monocyte-derived dendritic cells modulates innate immune response

Virology. 2014 Apr:454-455:197-205. doi: 10.1016/j.virol.2014.02.018. Epub 2014 Mar 7.

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) closely resembled severe acute respiratory syndrome coronavirus (SARS-CoV) in disease manifestation as rapidly progressive acute pneumonia with multi-organ dysfunction. Using monocyte-derived-dendritic cells (Mo-DCs), we discovered fundamental discrepancies in the outcome of MERS-CoV- and SARS-CoV-infection. First, MERS-CoV productively infected Mo-DCs while SARS-CoV-infection was abortive. Second, MERS-CoV induced significantly higher levels of IFN-γ, IP-10, IL-12, and RANTES expression than SARS-CoV. Third, MERS-CoV-infection induced higher surface expression of MHC class II (HLA-DR) and the co-stimulatory molecule CD86 than SARS-CoV-infection. Overall, our data suggests that the dendritic cell can serve as an important target of viral replication and a vehicle for dissemination. MERS-CoV-infection in DCs results in the production of a rich combination of cytokines and chemokines, and modulates innate immune response differently from that of SARS-CoV-infection. Our findings may help to explain the apparent discrepancy in the pathogenicity between MERS-CoV and SARS-CoV.

Keywords: Antigen-presentation; Cytokine and chemokine response; MERS-CoV; Pathogenesis; SARS-CoV; Viral replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-2 Antigen / metabolism
  • Cells, Cultured
  • Coronavirus / growth & development*
  • Coronavirus / immunology*
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology*
  • Healthy Volunteers
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunity, Innate*

Substances

  • B7-2 Antigen
  • CD86 protein, human
  • Cytokines
  • Histocompatibility Antigens Class II