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

doi:10.1016/j.virol.2021.08.002

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

Plant Pathology

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	1-19
Number of pages	19
Journal	Virology
Volume	563
DOIs	https://doi.org/10.1016/j.virol.2021.08.002
State	Published - Nov 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

Funding

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. 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.

Funders	Funder number
Institute for Neurodegenerative Disease, University of California
National Science Foundation Arctic Social Science Program	MCB-1517751, IOS-1922895
U.S. Department of Agriculture
US Department of Agriculture National Institute of Food and Agriculture, Agriculture and Food Research Initiative	2020-70410-32901, KY012042

Keywords

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

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2021.08.002

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title = "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",

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.",

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author = "Melissa Molho and Prasanth, {K. Reddisiva} and Judit Pogany and Nagy, {Peter D.}",

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doi = "10.1016/j.virol.2021.08.002",

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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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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