TY - JOUR
T1 - Anti-Vpr activity of a yeast chaperone protein
AU - Benko, Zsigmond
AU - Liang, Dong
AU - Agbottah, Emmanuel
AU - Hou, Jason
AU - Chiu, Karen
AU - Yu, Min
AU - Innis, Scott
AU - Reed, Patrick
AU - Kabat, William
AU - Elder, Robert T.
AU - Di Marzio, Paola
AU - Taricani, Lorena
AU - Ratner, Lee
AU - Young, Paul G.
AU - Bukrinsky, Michael
AU - Zhao, Richard Yuqi
PY - 2004/10
Y1 - 2004/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=4644251531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4644251531&partnerID=8YFLogxK
U2 - 10.1128/JVI.78.20.11016-11029.2004
DO - 10.1128/JVI.78.20.11016-11029.2004
M3 - Article
C2 - 15452222
AN - SCOPUS:4644251531
SN - 0022-538X
VL - 78
SP - 11016
EP - 11029
JO - Journal of Virology
JF - Journal of Virology
IS - 20
ER -