Targeting conserved co-opted host factors to block virus replication: Using allosteric inhibitors of the cytosolic Hsp70s to interfere with tomato bushy stunt virus replication

Melissa Molho, K. Reddisiva Prasanth, Judit Pogany, Peter D. Nagy

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1-19
Number of pages19
JournalVirology
Volume563
DOIs
StatePublished - Nov 2021

Bibliographical note

Funding Information:
The authors thank to Jason E. Gestwicki (Department of Pharmaceutical Chemistry and the Institute for Neurodegenerative Disease, University of California at San Francisco, San Francisco, California) for providing the Hsp70 allosteric inhibitors. This work was supported by the National Science Foundation (MCB-1517751 and IOS-1922895), USDA (NIFA, 2020-70410-32901) and a USDA hatch grant (KY012042) to PDN.

Funding Information:
The authors thank to Jason E. Gestwicki (Department of Pharmaceutical Chemistry and the Institute for Neurodegenerative Disease, University of California at San Francisco, San Francisco, California) for providing the Hsp70 allosteric inhibitors. This work was supported by the National Science Foundation ( MCB-1517751 and IOS-1922895 ), USDA ( NIFA , 2020-70410-32901 ) and a USDA hatch grant ( KY012042 ) to PDN.

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

  • Allosterick inhibitors
  • Antiviral
  • Carnation Italian ringspot virus
  • Plant
  • Replicase
  • Tomato bushy stunt virus
  • Virus replication
  • Yeast
  • hsp70

ASJC Scopus subject areas

  • Virology

Fingerprint

Dive into the research topics of 'Targeting conserved co-opted host factors to block virus replication: Using allosteric inhibitors of the cytosolic Hsp70s to interfere with tomato bushy stunt virus replication'. Together they form a unique fingerprint.

Cite this