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Journal of Virology, November 1998, p. 8659-8668, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Multimer Formation Is Not Essential for Nuclear Export of Human T-Cell Leukemia Virus Type 1 Rex trans-Activator Protein

Peter Heger,1 Olaf Rosorius,1 Claudia Koch,1 Georg Casari,2 Ralph Grassmann,1 and Joachim Hauber1,*

Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen,1 and Lion AG, D-69120 Heidelberg,2 Germany

Received 12 May 1998/Accepted 17 July 1998

The Rex trans-regulatory protein of human T-cell leukemia virus type 1 (HTLV-1) is required for the nuclear export of incompletely spliced and unspliced viral mRNAs and is therefore essential for virus replication. Rex is a nuclear phosphoprotein that directly binds to its cis-acting Rex response element RNA target sequence and constantly shuttles between the nucleus and cytoplasm. Moreover, Rex induces nuclear accumulation of unspliced viral RNA. Three protein domains which mediate nuclear import-RNA binding, nuclear export, and Rex oligomerization have been mapped within the 189-amino-acid Rex polypeptide. Here we identified a different region in the carboxy-terminal half of Rex which is also required for biological activity. In inactive mutants with mutations that map within this region, as well as in mutants that are deficient in Rex-specific multimerization, Rex trans activation could be reconstituted by fusion to a heterologous leucine zipper dimerization interface. The intracellular trafficking capabilities of wild-type and mutant Rex proteins reveal that biologically inactive and multimerization-deficient Rex mutants are still efficiently translocated from the nucleus to the cytoplasm. This observation indicates that multimerization is essential for Rex function but is not required for nuclear export. Finally, we are able to provide an improved model of the HTLV-1 Rex domain structure.

* Corresponding author. Mailing address: Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany. Phone: 49-9131-852 6182. Fax: 49-9131-852 2101. E-mail: jmhauber{at}viro.med.uni-erlangen.de.

Journal of Virology, November 1998, p. 8659-8668, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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