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J Virol, May 1998, p. 3991-3998, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Infectious Molecular Clones with the Nonhomologous Dimer Initiation Sequences Found in Different Subtypes of Human Immunodeficiency Virus Type 1 Can Recombine and Initiate a Spreading Infection In Vitro

Daniel C. St. Louis,1,* Deanna Gotte,1 Eric Sanders-Buell,1 David W. Ritchey,1 Mika O. Salminen,1,2 Jean K. Carr,1 and Francine E. McCutchan1

The Henry M. Jackson Foundation for the Advancement of Military Medicine and Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland 20850,1 and National Public Health Institute, Helsinki, Finland2

Received 3 October 1997/Accepted 15 January 1998

Recombinant forms of human immunodeficiency virus type 1 (HIV-1) have been shown to be of major importance in the global AIDS pandemic. Viral RNA dimer formation mediated by the dimerization initiation sequence (DIS) is believed to be essential for viral genomic RNA packaging and therefore for RNA recombination. Here, we demonstrate that HIV-1 recombination and replication are not restricted by variant DIS loop sequences. Three DIS loop forms found among HIV-1 isolates, DIS (CG), DIS (TA), and DIS (TG), when introduced into deletion mutants of HIV-1 recombined efficiently, and the progeny virions replicated with comparable kinetics. A fourth DIS loop form, containing an artificial AAAAAA sequence disrupting the putative DIS loop-loop interactions [DIS (A6)], supported efficient recombination with DIS loop variants; however, DIS (A6) progeny virions exhibited a modest replication disadvantage in mixed cultures. Our studies indicate that the nonhomologous DIS sequences found in different HIV-1 subtypes are not a primary obstacle to intersubtype recombination.

* Corresponding author. Mailing address: Henry M. Jackson Foundation Research Laboratory, 1600 E. Gude Dr., Rockville, MD 20850. Phone: (301) 295-1076. Fax: (301) 295-0376. E-mail: StLouisd{at}NMRIPO.NMRI.NNMC.NAVY.MIL.

J Virol, May 1998, p. 3991-3998, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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