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Nucleic Acids Research Advance Access published online on August 7, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm564
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

Circularization of the HIV-1 RNA genome

Marcel Ooms, Truus E. M. Abbink, Chi Pham and Ben Berkhout*

Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, The Netherlands

*To whom correspondence should be addressed. Tel: +31 205 664 822; Fax: +31 206 916 531; Email: b.berkhout{at}amc.uva.nl

Received May 21, 2007. Revised July 6, 2007. Accepted July 7, 2007.

Genomic RNA circularization has been proposed for several RNA viruses. In this study, we examined if the 5' and 3' ends of the 9-kb HIV-1 RNA genome can interact. In vitro assays demonstrated a specific interaction between transcripts encompassing the 5' and 3' terminal 1 kb, suggesting that the HIV-1 RNA genome can circularize. Truncation of the transcripts indicated that the 5'–3' interaction is formed by 600–700 nt in the gag open reading frame and the terminal 123 nt of the genomic RNA. Detailed RNA structure probing indicates that sequences flanking the 3' TAR hairpin interact with complementary sequences in the gag gene. Phylogenetic analysis indicates that all HIV-1 subtypes can form the 5'/3' interaction despite considerable sequence divergence, suggesting an important role of RNA circularization in the HIV-1 replication cycle.


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