HIV-1 Vpr induces interferon-stimulated genes in human monocyte-derived macrophages

PLoS One. 2014 Aug 29;9(8):e106418. doi: 10.1371/journal.pone.0106418. eCollection 2014.

Abstract

Macrophages act as reservoirs of human immunodeficiency virus type 1 (HIV-1) and play an important role in its transmission to other cells. HIV-1 Vpr is a multi-functional protein involved in HIV-1 replication and pathogenesis; however, its exact role in HIV-1-infected human macrophages remains poorly understood. In this study, we used a microarray approach to explore the effects of HIV-1 Vpr on the transcriptional profile of human monocyte-derived macrophages (MDMs). More than 500 genes, mainly those involved in the innate immune response, the type I interferon pathway, cytokine production, and signal transduction, were differentially regulated (fold change >2.0) after infection with a recombinant adenovirus expressing HIV-1 Vpr protein. The differential expression profiles of select interferon-stimulated genes (ISGs) and genes involved in the innate immune response, including STAT1, IRF7, MX1, MX2, ISG15, ISG20, IFIT1, IFIT2, IFIT3, IFI27, IFI44L, APOBEC3A, DDX58 (RIG-I), TNFSF10 (TRAIL), and RSAD2 (viperin) were confirmed by real-time quantitative PCR and were consistent with the microarray data. In addition, at the post-translational level, HIV-1 Vpr induced the phosphorylation of STAT1 at tyrosine 701 in human MDMs. These results demonstrate that HIV-1 Vpr leads to the induction of ISGs and expand the current understanding of the function of Vpr and its role in HIV-1 immune pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Dependovirus / genetics*
  • Dependovirus / physiology
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation* / drug effects
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunity, Innate
  • Interferon Regulatory Factor-7 / genetics
  • Interferon Regulatory Factor-7 / metabolism
  • Interferons / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / virology*
  • Oligonucleotide Array Sequence Analysis / methods*
  • Phosphorylation
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • vpr Gene Products, Human Immunodeficiency Virus / genetics
  • vpr Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • IRF7 protein, human
  • Interferon Regulatory Factor-7
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • vpr Gene Products, Human Immunodeficiency Virus
  • vpr protein, Human immunodeficiency virus 1
  • Interferons

Associated data

  • GEO/GSE56591

Grant support

This work was supported by a Health Sciences Research Grant from the Ministry of Health, Labor and Welfare of Japan, Research on HIV/AIDS: (http://www.jhsf.or.jp/English/index_e.html) and the Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellowship for Foreign Researchers (http://www.jsps.go.jp/english/e-fellow/postdoctoral.html). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.