Human cytomegalovirus triggers the assembly of AIM2 inflammasome in THP-1-derived macrophages

J Med Virol. 2017 Dec;89(12):2188-2195. doi: 10.1002/jmv.24846. Epub 2017 Aug 29.

Abstract

Absent in melanoma 2 (AIM2) inflammasome is a multiprotein complex which plays a pivotal role in the host immune response to multiple pathogens. The role of AIM2 in human cytomegalovirus (HCMV) infection is poorly studied. Thus, using a small inference RNA (siRNA) approach and THP-1 derived macrophage cells infected with HCMV AD169 strain, we investigated the impact of HCMV infection on AIM2-mediated molecular events. Compared to wild-type cells, AIM2-defiecient macrophages showed a limited ability to activate caspase-1, process IL-1β, and induce cell death. In addition, AIM2-defiecient cells were unable to efficiently control HCMV infection, as the transcription of virus DNA polymerase gene UL54 and major tegument protein gene UL83 were higher compared to wild-type cells. In conclusion, HCMV infection induces an AIM2 inflammasome response, which negatively influences viral life cycle.

Keywords: human cytomegalovirus; innate immunity; interleukin; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Cell Death
  • Cytomegalovirus / immunology*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • DNA-Directed DNA Polymerase / genetics
  • Humans
  • Immunity, Innate*
  • Inflammasomes / genetics*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Macrophages / immunology*
  • Macrophages / virology
  • Phosphoproteins / genetics
  • RNA, Small Interfering
  • Viral Matrix Proteins / genetics
  • Viral Proteins / genetics

Substances

  • AIM2 protein, human
  • DNA-Binding Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Phosphoproteins
  • RNA, Small Interfering
  • UL54 protein, Human herpesvirus 5
  • Viral Matrix Proteins
  • Viral Proteins
  • cytomegalovirus matrix protein 65kDa
  • DNA-Directed DNA Polymerase
  • Caspase 1