Host restriction factor SAMHD1 limits human T cell leukemia virus type 1 infection of monocytes via STING-mediated apoptosis.

Abstract

Human T cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T cell leukemia and HTLV-1-associated myelopathies. In addition to T cells, HTLV-1 infects cells of the myeloid lineage, which play critical roles in the host innate response to viral infection. Investigating the monocyte depletion observed during HTLV-1 infection, we discovered that primary human monocytes infected with HTLV-1 undergo abortive infection accompanied by apoptosis dependent on SAMHD1, a host restriction factor that hydrolyzes endogenous dNTPs to below the levels required for productive reverse transcription. Reverse transcription intermediates (RTI) produced in the presence of SAMHD1 induced IRF3-mediated antiviral and apoptotic responses. Viral RTIs complexed with the DNA sensor STING to trigger formation of an IRF3-Bax complex leading to apoptosis. This study provides a mechanistic explanation for abortive HTLV-1 infection of monocytes and reports a link between SAMHD1 restriction, HTLV-1 RTI sensing by STING, and initiation of IRF3-Bax driven apoptosis.

• Authors: Alexandre Sze, S Mehdi Belgnaoui, David Olagnier, Rongtuan Lin, John Hiscott, Julien van Grevenynghe
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 14 Issue 4 Pg. 422-34 (Oct 16 2013) ISSN: 1934-6069 [Electronic] United States
• PMID: 24139400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• BAX protein, human
• IRF3 protein, human
• Interferon Regulatory Factor-3
• Membrane Proteins
• STING1 protein, human
• bcl-2-Associated X Protein
• SAM Domain and HD Domain-Containing Protein 1
• SAMHD1 protein, human
• Monomeric GTP-Binding Proteins

Topics

• Apoptosis
• Human T-lymphotropic virus 1 (immunology)
• Humans
• Interferon Regulatory Factor-3 (metabolism)
• Membrane Proteins (metabolism)
• Monocytes (immunology, virology)
• Monomeric GTP-Binding Proteins (metabolism)
• SAM Domain and HD Domain-Containing Protein 1
• bcl-2-Associated X Protein (metabolism)