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Cell Host Microbe. 2013 Oct 16;14(4):422-34. doi: 10.1016/j.chom.2013.09.009.

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

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1
Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada.

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.

PMID:
24139400
DOI:
10.1016/j.chom.2013.09.009
[Indexed for MEDLINE]
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