Anti-Vpr activity of a yeast chaperone protein

Zsigmond Benko, Dong Liang, Emmanuel Agbottah, Jason Hou, Karen Chiu, Min Yu, Scott Innis, Patrick Reed, William Kabat, Robert T. Elder, Paola Di Marzio, Lorena Taricani, Lee Ratner, Paul G. Young, Michael Bukrinsky, Richard Yuqi Zhao

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) exerts multiple effects on viral and host cellular activities during viral infection, including unclear transport of the proviral integration complex, induction of cell cycle G 2 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.

Original languageEnglish
Pages (from-to)11016-11029
Number of pages14
JournalJournal of virology
Volume78
Issue number20
DOIs
StatePublished - Oct 1 2004

Fingerprint Dive into the research topics of 'Anti-Vpr activity of a yeast chaperone protein'. Together they form a unique fingerprint.

  • Cite this

    Benko, Z., Liang, D., Agbottah, E., Hou, J., Chiu, K., Yu, M., Innis, S., Reed, P., Kabat, W., Elder, R. T., Di Marzio, P., Taricani, L., Ratner, L., Young, P. G., Bukrinsky, M., & Zhao, R. Y. (2004). Anti-Vpr activity of a yeast chaperone protein. Journal of virology, 78(20), 11016-11029. https://doi.org/10.1128/JVI.78.20.11016-11029.2004