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Host restriction factor SAMHD1 limits human T-cell leukemia virus (HTLV-1) infection of primary monocytes via the innate immune sensor STING

  • Alexandre Sze1,
  • S Mehdi Belgnaoui1,
  • Rongtuan Lin1,
  • Julien van Grevenynghe1, 2 and
  • John Hiscott2Email author
Retrovirology201411(Suppl 1):O19

Published: 7 January 2014


Abortive InfectionIRF3 ActivationMonocyte ApoptosisHost Restriction FactorSensor Sting

Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T cell leukemia (ATL) and other HTLV-1 associated neurological disorders. Unlike most retroviruses, cell-free HTLV-1 virions are poorly infectious and do not stably infect its primary CD4+ T lymphocyte target. However, HTLV-1 efficiently infects cells of the myeloid lineage, leading to productive infection of myeloid cells. Here, we investigate the mechanisms underlying monocyte infection by HTLV-1 and demonstrate that HTLV-1 infection induced apoptosis of monocytes in a SAMHD1-dependent manner. SAMHD1, a deoxynucleoside triphosphate triphosphohydrolase, functions as a restriction factor that limits HIV-1 replication by reducing the availability of deoxynucleosidetriphosphates (dNTPs) required for reverse transcription. RNAi-mediated silencing of SAMHD1 inhibited monocyte apoptosis, while addition of exogenous dNTPs, or pre-treatment with azidothymidine (AZT) to block reverse transcription also inhibited apoptosis. To investigate a role for reverse transcription intermediates (RTI) in triggering apoptosis, a biotinylated 90 nucleotide RTI from the U5 region of HTLV-1 was introduced into monocytes; strikingly, the biotinylated RTI induced apoptosis and bound to the DNA sensor STING - which mediates the antiviral response via IRF3 activation. We further demonstrated that STING-mediated apoptosis in infected monocytes required the generation of a pro-apoptotic complex between IRF3 and the Bcl-2 protein Bax. These studies provide a mechanistic explanation for HTLV-1 abortive infection of monocytes and report a link between SAMHD1 restriction of reverse transcription, sensing of retroviral reverse transcription intermediates by STING, and the initiation of IRF3-Bax driven apoptosis.

Authors’ Affiliations

Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, Canada
Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, USA


© Sze et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.