HTLV-1 evades type I interferon antiviral signaling by inducing the suppressor of cytokine signaling 1 (SOCS1)

Human t cell leukemia virus type 1 (htlv-1) is the etiologic agent of adult t cell leukemia (atl) and the neurological disorder htlv-1-associated myelopathy/tropical spastic paraparesis (ham/tsp). although the majority of htlv-1-infected individuals remain asymptomatic carriers (ac) during their lifetime,2-5% will develop either atl or ham/tsp,but never both. to better understand the gene expression changes in htlv-1-associated diseases,we examined the mrna profiles of cd4+ t cells isolated from 7 atl,12 ham/tsp,11 ac and 8 non-infected controls. using genomic approaches followed by bioinformatic analysis,we identified gene expression pattern characteristic of htlv-1 infected individuals and particular disease states. of particular interest,the suppressor of cytokine signaling 1-socs1-was upregulated in ham/tsp and ac patients but not in atl. moreover,socs1 was positively correlated with the expression of htlv-1 mrna in ham/tsp patient samples. in primary pbmcs transfected with a htlv-1 proviral clone and in htlv-1-transformed mt-2 cells,htlv-1 replication correlated with induction of socs1 and inhibition of ifn-a/b and ifn-stimulated gene expression. targeting socs1 with sirna restored type i ifn production and reduced htlv-1 replication in mt-2 cells. conversely,exogenous expression of socs1 resulted in enhanced htlv-1 mrna synthesis. in addition to inhibiting signaling downstream of the ifn receptor,socs1 inhibited ifn-b production by targeting irf3 for ubiquitination and proteasomal degradation. these observations identify a novel socs1 driven mechanism of evasion of the type i ifn antiviral response against htlv-1 © 2010 olière et al.