Expression of alternatively spliced human T-cell leukemia virus type 1 mRNAs is influenced by mitosis and by a novel cis-acting regulatory sequence

Ilaria Cavallari, Francesca Rende, Marion K. Bona, Joanna Sztuba-Solinska, Micol Silic-Benussi, Martina Tognon, Stuart F J LeGrice, Genoveffa Franchini, Donna M. D'Agostino, Vincenzo Ciminale

Research output: Contribution to journalArticlepeer-review

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) expression depends on the concerted action of Tax, which drives transcription of the viral genome, and Rex, which favors expression of incompletely spliced mRNAs and determines a 2-phase temporal pattern of viral expression. In the present study, we investigated the Rex dependence of the complete set of alternatively spliced HTLV-1 mRNAs. Analyses of cells transfected with Rex-wild-type and Rex-knockout HTLV-1 molecular clones using splice site-specific quantitative reverse transcription (qRT)-PCR revealed that mRNAs encoding the p30Tof, p13, and p12/8 proteins were Rex dependent, while the p21rex mRNA was Rex independent. These findings provide a rational explanation for the intermediate-late temporal pattern of expression of the p30tof, p13, and p12/8 mRNAs described in previous studies. All the Rex-dependent mRNAs contained a 75-nucleotide intronic region that increased the nuclear retention and degradation of a reporter mRNA in the absence of other viral sequences. Selective 2=-hydroxyl acylation analyzed by primer extension (SHAPE) analysis revealed that this sequence formed a stable hairpin structure. Cell cycle synchronization experiments indicated that mitosis partially bypasses the requirement for Rex to export Rex-dependent HTLV-1 transcripts. These findings indicate a link between the cycling properties of the host cell and the temporal pattern of viral expression/latency that might influence the ability of the virus to spread and evade the immune system.

Original languageEnglish
Pages (from-to)1486-1498
Number of pages13
JournalJournal of Virology
Volume90
Issue number3
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Immunology
  • Virology

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