Abstract
BackgroundThe role of innate immunity in general and of type I interferon (IFN-I) in particular in HTLV-1 pathogenesis is still a matter of debate. ADAR1-p150 is an Interferon Stimulated Gene (ISG) induced by IFN-I that can edit viral RNAs. We therefore investigated whether it could play the role of an anti-HTLV factor.ResultsWe demonstrate here that ADAR1 is also expressed in the absence of IFN stimulation in activated primary T-lymphocytes that are the natural target of this virus and in HTLV-1 or HTLV-2 chronically infected T-cells. ADAR1 expression is also increased in primary lymphocytes obtained from HTLV-1 infected individuals. We show that ADAR1 enhances HTLV-1 and HTLV-2 infection in T-lymphocytes and that this proviral effect is independent from its editing activity. ADAR1 expression suppresses IFN-α inhibitory effect on HTLV-1 and HTLV-2 and acts through the repression of PKR phosphorylation.DiscussionThis study demonstrates that two interferon stimulated genes, i.e. PKR and ADAR1 have opposite effects on HTLV replication in vivo. The balanced expression of those proteins could determine the fate of the viral cycle in the course of infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-014-0093-9) contains supplementary material, which is available to authorized users.
Highlights
The role of innate immunity in general and of type I interferon (IFN-I) in particular in Human T-cell leukemia virus type 1 (HTLV-1) pathogenesis is still a matter of debate
In another set of experiments using the exquisitely sensitive 3DI-PCR technique [56], we have shown that HTLV-2 and simian T-cell leukemia virus type 3 (STLV-3) genomes can be edited by ADAR1 in cells transfected with HTLV-2 or STLV-3 molecular clones and an ADAR1-encoding plasmid [57]
We show that ADAR1 enhances HTLV-1 and HTLV-2 infection in T-lymphocytes and that this proviral effect is independent from its editing activity
Summary
The role of innate immunity in general and of type I interferon (IFN-I) in particular in HTLV-1 pathogenesis is still a matter of debate. Human T-cell leukemia virus type 1 (HTLV-1) was the first human oncoretrovirus to be discovered [1,2] It infects 5 to 10 million people worldwide [3]. Despite similarities with HTLV-1 in its genomic organization, HTLV-2 is only associated with rare cases of HAM/TSPlike diseases but does not promote leukemia or lymphoma [7,8]. The cause for such differences is a matter of investigation [9,10,11,12,13,14,15,16,17,18]. Multiple reports already pointed out the key roles played both by Tax and HTLV-1 antisense-encoded protein in cell transformation [18,19,20]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call