HTLV-1-infected T cells evade the antiproliferative action of IFN-beta

Human T-cell lymphotropic virus type I (HTLV-I)-infected T-cell clones ente r the S-phase of the cell cycle in the absence of exogenous IL-2. The pathw ay by which HTLV-I activates the host T cell may circumvent normal immunore gulatory mechanisms and thus be important for the pathogenesis of HTLV-I-in duced diseases. The early control of viral infections is in part mediated b y interferons (IFNs), which possess both antiviral and antiproliferative fu nctions. In order to investigate the antiproliferative effect of IFN-beta o n HTLV-l-induced T-cell activation, we generated T-cell clones from patient s with HTLV-I-associated myelopathy/tropical spastic paraparesis by single- cell cloning under limiting dilution conditions. Here we demonstrate that H TLV-l-induced T-cell proliferation is resistant to the antiproliferative ac tion of IFN-beta. Moreover, HTLV-I-infected T-cell clones continue to const itutively secrete IFN-gamma in the presence of high doses of IFN-beta. HTLV -l-infected T cells express normal levels of IFNAR1 and are able to respond to IFN-beta by phosphorylation of STAT1 on Tyr(701), although they display a relative increase in phosphorylation of the transcriptionally inactive S TAT1 beta when compared with STAT1 alpha. Thus, HTLV-I promotes cell cycle progression in G(1) by a mechanism that overcomes inhibitory signals, there by circumventing an innate immune defense mechanism. (C) 1999 Academic Pres s.