ADAR1 Facilitates HIV-1 Replication in Primary CD4+ T Cells

PLoS One. 2015 Dec 2;10(12):e0143613. doi: 10.1371/journal.pone.0143613. eCollection 2015.

Abstract

Unlike resting CD4+ T cells, activated CD4+T cells are highly susceptible to infection of human immunodeficiency virus 1 (HIV-1). HIV-1 infects T cells and macrophages without activating the nucleic acid sensors and the anti-viral type I interferon response. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that displays antiviral activity against several RNA viruses. Mutations in ADAR1 cause the autoimmune disorder Aicardi-Goutieères syndrome (AGS). This disease is characterized by an inappropriate activation of the interferon-stimulated gene response. Here we show that HIV-1 replication, in ADAR1-deficient CD4+T lymphocytes from AGS patients, is blocked at the level of protein translation. Furthermore, viral protein synthesis block is accompanied by an activation of interferon-stimulated genes. RNA silencing of ADAR1 in Jurkat cells also inhibited HIV-1 protein synthesis. Our data support that HIV-1 requires ADAR1 for efficient replication in human CD4+T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / metabolism*
  • Adolescent
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / virology*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • HIV Infections / metabolism
  • HIV Infections / virology*
  • HIV-1 / pathogenicity*
  • Humans
  • Jurkat Cells
  • Male
  • RNA, Messenger / genetics
  • RNA, Viral / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Virus Replication*

Substances

  • RNA, Messenger
  • RNA, Viral
  • RNA-Binding Proteins
  • ADAR protein, human
  • Adenosine Deaminase

Grants and funding

This work was supported by European Union (EU) Seventh Framework Programme [Grant number: 241779] (Nuclease Immune Mediated Brain and Lupus-like conditions (NIMBL): natural history, pathophysiology, diagnostic and therapeutic modalities with application to other disorders of autoimmunity (http://ec.europa.eu/research/health/medical-research/rare-diseases/projects/nimbl_en.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.