Kinetics and intracellular compartmentalization of HTLV-1 gene expression: Nuclear retention of HBZ mRNAs

Francesca Rende, Ilaria Cavallari, Alberto Corradin, Micol Silic-Benussi, Frederic Toulza, Gianna M. Toffolo, Yuetsu Tanaka, Steven Jacobson, Graham P. Taylor, Donna M. D'Agostino, Charles R M Bangham, Vincenzo Ciminale

Research output: Contribution to journalArticlepeer-review

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) codes for 9 alternatively spliced transcripts and 2 major regulatory proteins named Tax and Rex that function at the transcriptional and posttranscriptional levels, respectively. We investigated the temporal sequence of HTLV-1 gene expression in primary cells from infected patients using splice site-specific quantitative RT-PCR. The results indicated a two-phase kinetics with the tax/rex mRNA preceding expression of other viral transcripts. Analysis of mRNA compartmentalization in cells transfected with HTLV-1 molecular clones demonstrated the strict Rex-dependency of the two-phase kinetics and revealed strong nuclear retention of HBZ mRNAs, supporting their function as noncoding transcripts. Mathematical modeling underscored the importance of a delay between the functions of Tax and Rex, which was supported by experimental evidence of the longer half-life of Rex. These data provide evidence for a temporal pattern of HTLV-1 expression and reveal major differences in the intracellular compartmentalization of HTLV-1 transcripts.

Original languageEnglish
Pages (from-to)4855-4859
Number of pages5
JournalBlood
Volume117
Issue number18
DOIs
Publication statusPublished - May 5 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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