TY - JOUR
T1 - Targeting conserved co-opted host factors to block virus replication
T2 - Using allosteric inhibitors of the cytosolic Hsp70s to interfere with tomato bushy stunt virus replication
AU - Molho, Melissa
AU - Prasanth, K. Reddisiva
AU - Pogany, Judit
AU - Nagy, Peter D.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/11
Y1 - 2021/11
N2 - To further our understanding of the pro-viral roles of the host cytosolic heat shock protein 70 (Hsp70) family, we chose the conserved Arabidopsis thaliana Hsp70-2 and the unique Erd2 (early response to dehydration 2), which contain Hsp70 domains. Based on in vitro studies with purified components, we show that AtHsp70-2 and AtErd2 perform pro-viral functions equivalent to that of the yeast Ssa1 Hsp70. These functions include activation of the tombusvirus RdRp, and stimulation of replicase assembly. Yeast-based complementation studies demonstrate that AtHsp70-2 or AtErd2 are present in the purified tombusvirus replicase. RNA silencing and over-expression studies in Nicotiana benthamiana suggest that both Hsp70-2 and Erd2 are co-opted by tomato bushy stunt virus (TBSV). Moreover, we used allosteric inhibitors of Hsp70s to inhibit replication of TBSV and related plant viruses in plants. Altogether, interfering with the functions of the co-opted Hsp70s could be an effective antiviral approach against tombusviruses in plants.
AB - To further our understanding of the pro-viral roles of the host cytosolic heat shock protein 70 (Hsp70) family, we chose the conserved Arabidopsis thaliana Hsp70-2 and the unique Erd2 (early response to dehydration 2), which contain Hsp70 domains. Based on in vitro studies with purified components, we show that AtHsp70-2 and AtErd2 perform pro-viral functions equivalent to that of the yeast Ssa1 Hsp70. These functions include activation of the tombusvirus RdRp, and stimulation of replicase assembly. Yeast-based complementation studies demonstrate that AtHsp70-2 or AtErd2 are present in the purified tombusvirus replicase. RNA silencing and over-expression studies in Nicotiana benthamiana suggest that both Hsp70-2 and Erd2 are co-opted by tomato bushy stunt virus (TBSV). Moreover, we used allosteric inhibitors of Hsp70s to inhibit replication of TBSV and related plant viruses in plants. Altogether, interfering with the functions of the co-opted Hsp70s could be an effective antiviral approach against tombusviruses in plants.
KW - Allosterick inhibitors
KW - Antiviral
KW - Carnation Italian ringspot virus
KW - Plant
KW - Replicase
KW - Tomato bushy stunt virus
KW - Virus replication
KW - Yeast
KW - hsp70
UR - http://www.scopus.com/inward/record.url?scp=85112440878&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85112440878&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2021.08.002
DO - 10.1016/j.virol.2021.08.002
M3 - Article
C2 - 34399236
AN - SCOPUS:85112440878
SN - 0042-6822
VL - 563
SP - 1
EP - 19
JO - Virology
JF - Virology
ER -