Open AccessADAR1 Facilitates HIV-1 Replication in Primary CD4+ T Cells
Author(s) -
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
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0143613
Subject(s) - jurkat cells , viral replication , biology , rna , virology , interferon , gene silencing , adenosine deaminase , rna silencing , gene , rna interference , microbiology and biotechnology , t cell , virus , adenosine , immune system , immunology , genetics , biochemistry
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.