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Molecular and Cellular Biology, March 2001, p. 2133-2143, Vol. 21, No. 6
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.6.2133-2143.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

RNA Trafficking Signals in Human Immunodeficiency Virus Type 1

Andrew J. Mouland,1 Hongbin Xu,2 Hongyi Cui,2 Winfried Krueger,2 Trent P. Munro,3 Melanie Prasol,2 Johanne Mercier,1 David Rekosh,4 Ross Smith,3 Elisa Barbarese,2 Eric A. Cohen,1 and John H. Carson2,*

Laboratory of Human Retrovirology, Department of Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada1; University of Queensland, Brisbane, Queensland, Australia3; University of Virginia, Charlottesville, Virginia4; and University of Connecticut Health Center, Farmington, Connecticut2

Received 24 August 2000/Returned for modification 26 September 2000/Accepted 14 November 2000

Intracellular trafficking of retroviral RNAs is a potential mechanism to target viral gene expression to specific regions of infected cells. Here we show that the human immunodeficiency virus type 1 (HIV-1) genome contains two sequences similar to the hnRNP A2 response element (A2RE), a cis-acting RNA trafficking sequence that binds to the trans-acting trafficking factor, hnRNP A2, and mediates a specific RNA trafficking pathway characterized extensively in oligodendrocytes. The two HIV-1 sequences, designated A2RE-1, within the major homology region of the gag gene, and A2RE-2, in a region of overlap between the vpr and tat genes, both bind to hnRNP A2 in vitro and are necessary and sufficient for RNA transport in oligodendrocytes in vivo. A single base change (A8G) in either sequence reduces hnRNP A2 binding and, in the case of A2RE-2, inhibits RNA transport. A2RE-mediated RNA transport is microtubule and hnRNP A2 dependent. Differentially labelled gag and vpr RNAs, containing A2RE-1 and A2RE-2, respectively, coassemble into the same RNA trafficking granules and are cotransported to the periphery of the cell. tat RNA, although it contains A2RE-2, is not transported as efficiently as vpr RNA. An A2RE/hnRNP A2-mediated trafficking pathway for HIV RNA is proposed, and the role of RNA trafficking in targeting HIV gene expression is discussed.

* Corresponding author. Mailing address: Department of Biochemistry, University of Connecticut Health Center, Farmington, CT 06030. Phone: (860) 679-2130. Fax: (860) 679-3408. E-mail: jcarson{at}nso2.uchc.edu.

Molecular and Cellular Biology, March 2001, p. 2133-2143, Vol. 21, No. 6
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.6.2133-2143.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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