RNA stability regulates human T cell leukemia virus type 1 gene expression in chronically-infected CD4 T cells

•PMA treatment rapidly and transiently increases HTLV-1 RNA and protein expression.•PMA induces increased tax/rex mRNA stability in latently infected T cells.•Increased tax/rex mRNA and protein leads to induction of other HTLV-1 proteins.•Increased tax/rex RNA stability is a new mechanism for activation of latent HTLV-1.

Regulation of expression of HTLV-1 gene products from integrated proviruses plays an important role in HTLV-1-associated disease pathogenesis. Previous studies have shown that T cell receptor (TCR)- and phorbol ester (PMA) stimulation of chronically infected CD4 T cells increases the expression of integrated HTLV-1 proviruses in latently infected cells, however the mechanism remains unknown. Analysis of HTLV-1 RNA and protein species following PMA treatment of the latently HTLV-1-infected, FS and SP T cell lines demonstrated rapid induction of tax/rex mRNA. This rapid increase in tax/rex mRNA was associated with markedly enhanced tax/rex mRNA stability while the stability of unspliced or singly spliced HTLV-1 RNAs did not increase. Tax/rex mRNA in the HTLV-1 constitutively expressing cell lines exhibited high basal stability even without PMA treatment. Our data support a model whereby T cell activation leads to increased HTLV-1 gene expression at least in part through increased tax/rex mRNA stability.

Graphical abstractDownload high-res image (153KB)Download full-size image