Transdominant human T-cell lymphotropic virus type I TAX1 mutant that fails to localize to the nucleus

Scott D. Gitlin, Paul F. Lindholm, Susan J. Marriott, John N. Brady*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Human T-cell lymphotropic virus type I (HTLV-I) encodes a 40-kDa nuclear transactivating phosphoprotein, TAX1. The results presented in this study demonstrate that deletion of amino acids 2 through 59 of TAX1 (Δ58 TAX1) decreased transactivation of the HTLV-I long terminal repeat 10- to 20-fold. S1 nuclease analysis revealed that the decrease in transactivation of the HTLV-I long terminal repeat was associated with a lack of RNA synthesis. In contrast to the nuclear localization of the wild-type TAX1 protein, indirect immunofluorescence analysis demonstrated that Δ58 TAX1 failed to localize to the nucleus, indicating that the TAX1 nuclear localization sequence is present in amino acids 2 through 59. Cotransfection of wild-type and mutant TAX1 DNAs resulted in the cytoplasmic accumulation of TAX1 and a 25-fold decrease in transactivation. Although several possibilities which may account for this transdominant effect exist, we favor a model in which Δ58 TAX1 interferes with the nuclear localization of wild-type TAX1 protein, perhaps by forming heterodimer complexes.

Original languageEnglish (US)
Pages (from-to)2612-2621
Number of pages10
JournalJournal of virology
Volume65
Issue number5
DOIs
StatePublished - 1991

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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