Key tethering function of Atg11 autophagy scaffold protein in formation of virus-induced membrane contact sites during tombusvirus replication

Yuanrong Kang; Wenwu Lin; Yuyan Liu; Peter D. Nagy

doi:10.1016/j.virol.2022.04.007

Key tethering function of Atg11 autophagy scaffold protein in formation of virus-induced membrane contact sites during tombusvirus replication

Yuanrong Kang, Wenwu Lin, Yuyan Liu, Peter D. Nagy

Plant Pathology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Positive-strand RNA viruses induce the biogenesis of viral replication organelles (VROs), which support viral replication in infected cells. VRO formation requires viral replication proteins, co-opted host factors and intracellular membranes. Here, we show that the conserved Atg11 autophagy scaffold protein is co-opted by Tomato bushy stunt virus (TBSV) via direct interactions with the viral replication proteins. Deletion of ATG11 in yeast or knockdown of the homologous Atg11 in plants led to reduced tombusvirus replication, thus indicating pro-viral function for Atg11. Based on co-purification, BiFC and proximity-labeling experiments, we find that Atg11 is co-opted to stabilize virus-induced membrane contact sites (vMCS) within VROs. We propose that the tethering and scaffold function of Atg11 is critical in vMCSs for lipid enrichment. Absence of Atg11 interferes with sterols enrichment in VROs, rendering VROs RNAi-sensitive. Altogether, the expanding roles of co-opted host proteins with tethering functions suggest that the tombusvirus VROs are elaborate structures.

Original language	English
Pages (from-to)	1-16
Number of pages	16
Journal	Virology
Volume	572
DOIs	https://doi.org/10.1016/j.virol.2022.04.007
State	Published - Jul 2022

Bibliographical note

Publisher Copyright:
© 2022

Funding

The authors are grateful to Drs. Judit Pogany and Shifeng Zhu for helping the project and helpful discussions. The authors acknowledge the initial contribution by Dr. N. Kovalev to adapt the protein proximity labeling approach. The authors thank Dr. J. Weismann (UCSF) for providing plasmids pJW1506 and pJW1234. 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
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

ASJC Scopus subject areas

Virology

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title = "Key tethering function of Atg11 autophagy scaffold protein in formation of virus-induced membrane contact sites during tombusvirus replication",

abstract = "Positive-strand RNA viruses induce the biogenesis of viral replication organelles (VROs), which support viral replication in infected cells. VRO formation requires viral replication proteins, co-opted host factors and intracellular membranes. Here, we show that the conserved Atg11 autophagy scaffold protein is co-opted by Tomato bushy stunt virus (TBSV) via direct interactions with the viral replication proteins. Deletion of ATG11 in yeast or knockdown of the homologous Atg11 in plants led to reduced tombusvirus replication, thus indicating pro-viral function for Atg11. Based on co-purification, BiFC and proximity-labeling experiments, we find that Atg11 is co-opted to stabilize virus-induced membrane contact sites (vMCS) within VROs. We propose that the tethering and scaffold function of Atg11 is critical in vMCSs for lipid enrichment. Absence of Atg11 interferes with sterols enrichment in VROs, rendering VROs RNAi-sensitive. Altogether, the expanding roles of co-opted host proteins with tethering functions suggest that the tombusvirus VROs are elaborate structures.",

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AU - Nagy, Peter D.

PY - 2022/7

Y1 - 2022/7

N2 - Positive-strand RNA viruses induce the biogenesis of viral replication organelles (VROs), which support viral replication in infected cells. VRO formation requires viral replication proteins, co-opted host factors and intracellular membranes. Here, we show that the conserved Atg11 autophagy scaffold protein is co-opted by Tomato bushy stunt virus (TBSV) via direct interactions with the viral replication proteins. Deletion of ATG11 in yeast or knockdown of the homologous Atg11 in plants led to reduced tombusvirus replication, thus indicating pro-viral function for Atg11. Based on co-purification, BiFC and proximity-labeling experiments, we find that Atg11 is co-opted to stabilize virus-induced membrane contact sites (vMCS) within VROs. We propose that the tethering and scaffold function of Atg11 is critical in vMCSs for lipid enrichment. Absence of Atg11 interferes with sterols enrichment in VROs, rendering VROs RNAi-sensitive. Altogether, the expanding roles of co-opted host proteins with tethering functions suggest that the tombusvirus VROs are elaborate structures.

AB - Positive-strand RNA viruses induce the biogenesis of viral replication organelles (VROs), which support viral replication in infected cells. VRO formation requires viral replication proteins, co-opted host factors and intracellular membranes. Here, we show that the conserved Atg11 autophagy scaffold protein is co-opted by Tomato bushy stunt virus (TBSV) via direct interactions with the viral replication proteins. Deletion of ATG11 in yeast or knockdown of the homologous Atg11 in plants led to reduced tombusvirus replication, thus indicating pro-viral function for Atg11. Based on co-purification, BiFC and proximity-labeling experiments, we find that Atg11 is co-opted to stabilize virus-induced membrane contact sites (vMCS) within VROs. We propose that the tethering and scaffold function of Atg11 is critical in vMCSs for lipid enrichment. Absence of Atg11 interferes with sterols enrichment in VROs, rendering VROs RNAi-sensitive. Altogether, the expanding roles of co-opted host proteins with tethering functions suggest that the tombusvirus VROs are elaborate structures.

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Key tethering function of Atg11 autophagy scaffold protein in formation of virus-induced membrane contact sites during tombusvirus replication

Abstract

Bibliographical note

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