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Journal of Virology, October 2004, p. 11016-11029, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11016-11029.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Anti-Vpr Activity of a Yeast Chaperone Protein

Children's Memorial Institute for Education and Research, Departments of Pediatrics and Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois,¹ Department of Microbiology and Tropical Medicine, George Washington University, Washington, D. C.,² Department of Biology, Queen's University, Kingston, Ontario, Canada,³ Department of Medicine, Washington University School of Medicine, St. Louis, Missouri⁴

Received 2 January 2004/ Accepted 7 June 2004

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) exerts multiple effects on viral and host cellular activities during viral infection, including nuclear transport of the proviral integration complex, induction of cell cycle G₂ arrest, and cell death. In this report, we show that a fission yeast chaperone protein Hsp16 inhibits HIV-1 by suppressing these Vpr activities. This protein was identified through three independent genome-wide screens for multicopy suppressors of each of the three Vpr activities. Consistent with the properties of a heat shock protein, heat shock-induced elevation or overproduction of Hsp16 suppressed Vpr activities through direct protein-protein interaction. Even though Hsp16 shows a stronger suppressive effect on Vpr in fission yeast than in mammalian cells, similar effects were also observed in human cells when fission yeast hsp16 was expressed either in vpr-expressing cells or during HIV-1 infection, indicating a possible highly conserved Vpr suppressing activity. Furthermore, stable expression of hsp16 prior to HIV-1 infection inhibits viral replication in a Vpr-dependent manner. Together, these data suggest that Hsp16 inhibits HIV-1 by suppressing Vpr-specific activities. This finding could potentially provide a new approach to studying the contribution of Vpr to viral pathogenesis and to reducing Vpr-mediated detrimental effects in HIV-infected patients.

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