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

Abstract

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.

The TP53-Induced Glycolysis and Apoptosis Regulator mediates cooperation between HTLV-1 p30II and the retroviral oncoproteins Tax and HBZ and is highly expressed in an in vivo xenograft model of HTLV-1-induced lymphoma

“…Moreover, p30 II posttranscriptionally inhibits Tax-dependent HTLV-1 gene expression by inhibiting the nuclear export of the pX -encoded tax/rex mRNA (Nicot et al, 2004; Younis et al, 2004; Younis et al, 2006). As Lin et al, 2017 have shown that the stability of tax/rex transcripts modulates HTLV-1 gene expression, it remains unclear whether the p30 II - tax/rex mRNA axis might affect the stability of these transcripts. Lentiviral p30 II interacts with the 20S proteasome activator, REGγ, and reduces the intracellular levels of the pro-apoptotic ataxia telangiectasia mutated (ATM) kinase and increases the survival of transduced Jurkat lymphocytes (Anupam et al, 2011; Doueiri et al, 2012).…”