Journal of Virology, May 2001, p. 4558-4569, Vol. 75, No. 10
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.10.4558-4569.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


Human Retrovirus Section1 and Human Retrovirus Pathogenesis Section,2 Basic Research Laboratory, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201
Received 27 November 2000/Accepted 20 February 2001
Human immunodeficiency virus (HIV) and all other lentiviruses utilize the essential viral protein Rev, which binds to RRE RNA, to export their unspliced and partially spliced mRNAs from the nucleus. We used a rev- and RRE-defective HIV type 1 (HIV-1) molecular clone in complementation experiments to establish a method for the rapid isolation of posttranscriptional regulatory elements from the mammalian genome by selecting for rescue of virus replication. Viruses rescued by this method contained a novel element with homology to rodent intracisternal A-particle (IAP) retroelements. A functional element was contained within a 247-nucleotide fragment named RNA transport element (RTE), which was able to promote replication of the Rev- and RRE-defective HIV-1 in both human lymphoid cell lines and primary lymphocytes, demonstrating its potent posttranscriptional function. RTE was functional in many cell types, indicating that the cellular factors that recognize RTE are widely expressed and evolutionarily conserved. RTE also promoted RNA export from Xenopus oocyte nuclei. RTE-mediated RNA transport was CRM1 independent, and RTE did not show high affinity for binding to mRNA export factor TAP/NXF1. Since CRM1 and TAP/NXF1 are critical export receptors associated with the two recognized mRNA export pathways, these results suggest that RTE functions via a distinct export mechanism. Taken together, our results identify a novel posttranscriptional control element that uses a conserved cellular export mechanism.
Present address: Laboratory of Virology, Istituto Superiore di
Sanità, Rome, Italy.
Present address: Institute of Experimental Genetics/AG BIODV,
GSF-National Research Center for Environment and Health, 85764 Neuherberg/Munich, Germany.
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