Research

Antagonistic interaction of HIV-1 Vpr with Hsf-mediated cellular heat shock response and Hsp16 in fission yeast (Schizosaccharomyces pombe)

Zsigmond Benko¹ , Dong Liang^1,2 , Emmanuel Agbottah⁴ , Jason Hou¹ , Lorena Taricani^3* , Paul G Young³ , Michael Bukrinsky⁴ and Richard Y Zhao^1,2

¹  Children's Memorial Research Center, Departments of Pediatrics, Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

²  Departments of Pathology, Microbiology-Immunology, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA

³  Department of Biology, Queen's University, Kingston, Ontario, Canada

⁴  Department of Microbiology and Tropical Medicine, George Washington University, Washington, DC, USA

author email corresponding author email* Contributed equally

Retrovirology 2007, 4:16doi:10.1186/1742-4690-4-16

Published:	7 March 2007

Abstract

Background

Expression of the HIV-1 vpr gene in human and fission yeast cells displays multiple highly conserved activities, which include induction of cell cycle G2 arrest and cell death. We have previously characterized a yeast heat shock protein 16 (Hsp16) that suppresses the Vpr activities when it is overproduced in fission yeast. Similar suppressive effects were observed when the fission yeast hsp16 gene was overexpressed in human cells or in the context of viral infection. In this study, we further characterized molecular actions underlying the suppressive effect of Hsp16 on the Vpr activities.

Results

We show that the suppressive effect of Hsp16 on Vpr-dependent viral replication in proliferating T-lymphocytes is mediated through its C-terminal end. In addition, we show that Hsp16 inhibits viral infection in macrophages in a dose-dependent manner. Mechanistically, Hsp16 suppresses Vpr activities in a way that resembles the cellular heat shock response. In particular, Hsp16 activation is mediated by a heat shock factor (Hsf)-dependent mechanism. Interestingly, vpr gene expression elicits a moderate increase of endogenous Hsp16 but prevents its elevation when cells are grown under heat shock conditions that normally stimulate Hsp16 production. Similar responsive to Vpr elevation of Hsp and counteraction of this elevation by Vpr were also observed in our parallel mammalian studies. Since Hsf-mediated elevation of small Hsps occurs in all eukaryotes, this finding suggests that the anti-Vpr activity of Hsps is a conserved feature of these proteins.

Conclusion

These data suggest that fission yeast could be used as a model to further delineate the potential dynamic and antagonistic interactions between HIV-1 Vpr and cellular heat shock responses involving Hsps.