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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.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Sze A,Belgnaoui SM,Olagnier D,Lin R,Hiscott J,van Grevenynghe J

doi

10.1016/j.chom.2013.09.009

subject

Has Abstract

pub_date

2013-10-16 00:00:00

pages

422-34

issue

4

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(13)00329-6

journal_volume

14

pub_type

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