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

Eloy Cuadrado; Thijs Booiman; John L van Hamme; Machiel H Jansen; Karel A van Dort; Adeline Vanderver; Gillian I Rice; Yanick J Crow; Neeltje A Kootstra; Taco W Kuijpers

doi:10.1371/journal.pone.0143613

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.

Authors

Eloy Cuadrado¹, Thijs Booiman^{1

2}, John L van Hamme^{1

2}, Machiel H Jansen¹, Karel A van Dort^{1

2}, Adeline Vanderver³, Gillian I Rice⁴, Yanick J Crow^{4

5}, Neeltje A Kootstra^{1

2}, Taco W Kuijpers^{1

6}

Affiliations

¹ Department of Experimental Immunology, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands.
² Sanquin Research, Landsteiner Laboratory and Center for Infection and Immunity (CINIMA) at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
³ Center for Genetic Medicine Research, Children's National Medical Center, Washington DC, United States of America.
⁴ Manchester Centre for Genomic Medicine, University of Manchester, Manchester Academic Health Sciences Centre (MAHSC), Manchester, United Kingdom.
⁵ INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Hôpital Necker, Paris, France.
⁶ Emma Children's Hospital, Dept of Pediatric Hematology, Immunology and Infectious disease, AMC, UvA, Amsterdam, The Netherlands.

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.