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Journal of Virology, December 2000, p. 10965-10974, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Retroviral cDNA Integration: Stimulation by HMG I Family Proteins

Ling Li, Kristine Yoder, Mark S. T. Hansen, Jennifer Olvera, Michael D. Miller,dagger and Frederic D. Bushman*

Infectious Disease Laboratory, The Salk Institute, La Jolla, California 92037

Received 23 June 2000/Accepted 18 August 2000

To replicate, a retrovirus must synthesize a cDNA copy of the viral RNA genome and integrate that cDNA into a chromosome of the host. We have investigated the role of a host cell cofactor, HMG I(Y) protein, in integration of human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukemia virus (MoMLV) cDNA. Previously we reported that HMG I(Y) cofractionates with HIV-1 preintegration complexes (PICs) isolated from freshly infected cells. PICs depleted of required components by treatment with high concentrations of salt could be reconstituted by addition of purified HMG I(Y) in vitro. Here we report studies using immunoprecipitation that indicate that HMG I(Y) is associated with MoMLV preintegration complexes. In mechanistic studies, we show for both HIV-1 and MoMLV that each HMG I(Y) monomer must contain multiple DNA binding domains to stimulate integration by HMG I(Y)-depleted PICs. We also find that HMG I(Y) can condense model HIV-1 or MoMLV cDNA in vitro as measured by stimulation of intermolecular ligation. This reaction, like reconstitution of integration, depends on the presence of multiple DNA binding domains in each HMG I(Y) monomer. These data suggest that binding of multivalent HMG I(Y) monomers to multiple cDNA sites compacts retroviral cDNA, thereby promoting formation of active integrase-cDNA complexes.

* Corresponding author. Mailing address: Infectious Disease Laboratory, The Salk Institute, 10010 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 453-4100, ext. 1630. Fax: (619) 554-0341. E-mail:bushman{at}salk.edu.

dagger Present address: Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486.

Journal of Virology, December 2000, p. 10965-10974, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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