Human T-cell leukemia virus type 1 blunts signaling by interferon alpha

Although many animal viruses block the interferon (IFN) signaling pathway, this issue has not been previously investigated in retrovirus-infected cells. For this purpose, an infectious molecular clone of human T-cell leukemia virus type I (HTLV-1) was transfected into 293T or HeLa cells and was found to reduce interferon-stimulated response element (ISRE) reporter activity. This effect was independent of expression of the polymerase or envelope products and independent of the ability of Tax to activate the NF kappa B transcriptional pathway. IFN-alpha activation of 6 of 7 endogenous ISRE-regulated genes was also variably reduced, but not IFN-gamma-activated response element-mediated expression of interferon regulatory factor 1. HTLV-1 reduced the phosphorylation of tyrosine kinase 2 (TYK2) and signal transducer and transcriptional activator 2 (STAT2), suggesting a specific effect of HTLV-1 on the ability of an adaptor tyrosine kinase to transfer an IFN signal to the STAT-transcriptional activator complex. (c) 2008 Elsevier Inc. All rights reserved.