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

Hsin-Ching Lin; Peter J Simon; Riza M Ysla; Steven L Zeichner; Gary Brewer; Arnold B Rabson

doi:10.1016/j.virol.2017.04.029

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

Virology. 2017 Aug:508:7-17. doi: 10.1016/j.virol.2017.04.029. Epub 2017 May 4.

Authors

Hsin-Ching Lin¹, Peter J Simon², Riza M Ysla³, Steven L Zeichner⁴, Gary Brewer³, Arnold B Rabson⁵

Affiliations

¹ Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, New Brunswick, NJ 08903, USA; Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
² Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
³ Department of Molecular Biology and Biochemistry, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.
⁴ Departments of Pediatrics and Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
⁵ Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, New Brunswick, NJ 08903, USA; Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA; Department of Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA. Electronic address: rabsonab@rwjms.rutgers.edu.

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.

Keywords: Arginosuccinate lyase; HTLV-1; Latency; RNA stability; Retroviruses.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes / virology*
Gene Expression Regulation, Viral*
Gene Products, tax / genetics
Gene Products, tax / metabolism
HTLV-I Infections / virology*
Human T-lymphotropic virus 1 / chemistry
Human T-lymphotropic virus 1 / genetics*
Human T-lymphotropic virus 1 / physiology
Humans
RNA Stability
RNA, Viral / chemistry*
RNA, Viral / genetics
Virus Latency

Substances

Gene Products, tax
RNA, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding