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Journal of Virology, April 2002, p. 3135-3144, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3135-3144.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Bipartite Signal for Genomic RNA Dimerization in Moloney Murine Leukemia Virus

Hinh Ly and Tristram G. Parslow*

Departments of Pathology and of Microbiology and Immunology, University of California, San Francisco, California

Received 27 September 2001/ Accepted 6 December 2001

Retroviral virions each contain two identical genomic RNA strands that are stably but noncovalently joined in parallel near their 5' ends. For certain viruses, this dimerization has been shown to depend on a unique RNA stem-loop locus, called the dimer initiation site (DIS), that efficiently homodimerizes through a palindromic base sequence in its loop. Previous studies with Moloney murine leukemia virus (Mo-MuLV) identified two alternative DIS loci that can each independently support RNA dimerization in vitro but whose relative contributions are unknown. We now report that both of these loci contribute to the assembly of the Mo-MuLV dimer. Using targeted deletions, point mutagenesis, and antisense oligonucleotides, we found that each of the two stem-loops forms as predicted and contributes independently to dimerization in vitro through a mechanism involving autocomplementary interactions of its loop. Disruption of either DIS locus individually reduced both the yield and the thermal stability of the in vitro dimers, whereas disruption of both eliminated dimerization altogether. Similarly, the thermal stability of virion-derived dimers was impaired by deletion of both DIS elements, and point mutations in either element produced defects in viral replication that correlated with their effects on in vitro RNA dimerization. These findings support the view that in some retroviruses, dimer initiation and stability involve two or more closely linked DIS loci which together align the nascent dimer strands in parallel and in register.

* Corresponding author. Mailing address: Department of Pathology, Box 0511, University of California, San Francisco, CA 94143-0511. Phone: (415) 476-1015. Fax: (415) 514-3165. E-mail: parslow{at}cgl.ucsf.edu.

Journal of Virology, April 2002, p. 3135-3144, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3135-3144.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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