Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis

J Virol. 2005 Jun;79(12):7819-26. doi: 10.1128/JVI.79.12.7819-7826.2005.

Abstract

The pathogenesis of severe acute respiratory syndrome (SARS) remains unclear. Macrophages are key sentinel cells in the respiratory system, and it is therefore relevant to compare the responses of human macrophages to infections with the SARS coronavirus (SARS-CoV) and other respiratory viruses. Primary human monocyte-derived macrophages were infected with SARS-CoV in vitro. Virus replication was monitored by measuring the levels of positive- and negative-strand RNA, by immunofluorescence detection of the SARS-CoV nucleoprotein, and by titration of the infectious virus. The gene expression profiles of macrophages infected with SARS-CoV, human coronavirus 229E, and influenza A (H1N1) virus were compared by using microarrays and real-time quantitative reverse transcriptase PCR. Secreted cytokines were measured with an enzyme-linked immunosorbent assay. SARS-CoV initiated viral gene transcription and protein synthesis in macrophages, but replication was abortive and no infectious virus was produced. In contrast to the case with human coronavirus 229E and influenza A virus, there was little or no induction of beta interferon (IFN-beta) in SARS-CoV-infected macrophages. Furthermore, SARS-CoV induced the expression of chemokines such as CXCL10/IFN-gamma-inducible protein 10 and CCL2/monocyte chemotactic protein 1. The poor induction of IFN-beta, a key component of innate immunity, and the ability of the virus to induce chemokines could explain aspects of the pathogenesis of SARS.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL10
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism
  • Cytokines / genetics*
  • Cytokines / metabolism*
  • Gene Expression Profiling
  • Humans
  • Macrophages / immunology*
  • Macrophages / virology*
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • SARS Virus / pathogenicity*
  • Severe Acute Respiratory Syndrome / immunology
  • Severe Acute Respiratory Syndrome / virology
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication

Substances

  • CCL2 protein, human
  • CXCL10 protein, human
  • Chemokine CCL2
  • Chemokine CXCL10
  • Chemokines, CXC
  • Cytokines
  • Viral Proteins