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Journal of Virology, October 2000, p. 9507-9514, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Rous Sarcoma Virus DR Posttranscriptional Elements Use a Novel RNA Export Pathway

Robert E. Paca,1 Robert A. Ogert,1,dagger Catherine S. Hibbert,1,Dagger Elisa Izaurralde,2 and Karen L. Beemon1,*

Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218,1 and EMBL, D-69117 Heidelberg, Germany2

Received 2 May 2000/Accepted 11 July 2000

Rous sarcoma virus (RSV), a simple retrovirus, needs to export unspliced viral RNA from the nucleus to the cytoplasm, circumventing the host cell restriction on cytoplasmic expression of intron-containing RNA. The cytoplasmic accumulation of full-length viral RNA is promoted by two cis-acting direct repeat (DR) elements that flank the src gene; at least one copy of the DR sequence is necessary for viral replication. We show here that the DR mediates export of a reporter construct from the nucleus, suggesting it is a constitutive transport element (CTE). In contrast, human immunodeficiency virus type 1 (HIV-1) and other complex retroviruses encode accessory proteins, Rev or Rex, which promote export of incompletely spliced viral transcripts. This RNA export pathway is CRM1 dependent and can be blocked by the cytotoxic agent leptomycin B. We show here that DR-mediated export is CRM1 independent, suggesting that RSV uses a different export pathway from that of HIV-1 and other complex retroviruses. The simian retroviruses have a CTE which interacts with the cellular Tap export protein. However, we were unable to detect binding of the RSV DR RNA to Tap, suggesting it may use a different export pathway from that of the simian retroviruses. These data suggest that the RSV DR element uses a novel nucleocytoplasmic export pathway.

* Corresponding author. Mailing address: Department of Biology, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218. Phone: (410) 516-7289. Fax: (410) 516-7292. E-mail: KLB{at}jhu.edu.

dagger Present address: Purdue Biopharma L.P., Princeton, NJ 08540.

Dagger Present address: NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702.

Journal of Virology, October 2000, p. 9507-9514, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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