Temporal regulation of HTLV-2 expression in infected cell lines and patients: evidence for distinct expression kinetics with nuclear accumulation of APH-2 mRNA

Retrovirology. 2012 Sep 13:9:74. doi: 10.1186/1742-4690-9-74.

Abstract

Background: Human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) are delta retroviruses with similar genetic organization. Although both viruses immortalize T-cells in vitro, they exhibit distinct pathogenic potential in vivo. To search for possible differences in its expression strategy with respect to HTLV-1, we investigated the pattern of HTLV-2 expression in infected cell lines and peripheral blood mononuclear cells (PBMCs) from infected patients using splice site-specific quantitative RT-PCR.

Findings: A novel alternative splice acceptor site for exon 2 was identified; its usage in env transcripts was found to be subtype-specific. Time-course analysis revealed a two-phase expression kinetics in an infected cell line and in PBMCs of two of the three patients examined; this pattern was reminiscent of HTLV-1. In addition, the minus-strand APH2 transcript was mainly detected in the nucleus, a feature that was similar to its HTLV-1 orthologue HBZ. In contrast to HTLV-1, expression of the mRNA encoding the main regulatory proteins Tax and Rex and that of the mRNAs encoding the p28 and truncated Rex inhibitors is skewed towards p28/truncated Rex inhibitors in HTLV-2.

Conclusion: Our data suggest a general converging pattern of expression of HTLV-2 and HTLV-1 and highlight peculiar differences in the expression of regulatory proteins that might influence the pathobiology of these viruses.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Viral*
  • Human T-lymphotropic virus 1 / genetics*
  • Human T-lymphotropic virus 1 / pathogenicity
  • Human T-lymphotropic virus 2 / genetics*
  • Human T-lymphotropic virus 2 / pathogenicity
  • Humans
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • RNA Splicing*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*

Substances

  • RNA, Viral