Sec62 restricts ER-replicating positive-strand RNA virus infections via UPR-dependent ER-phagy

Area of Science:

• Plant Virology
• Molecular Plant-Microbe Interactions
• Cellular Homeostasis

Background:

• Positive-strand RNA [(+)RNA] viruses remodel host endomembranes into viral replication organelles (VROs), disrupting cellular homeostasis.
• The mechanisms by which host cells restore organelle balance and how this impacts viral replication are not fully understood.

Purpose of the Study:

• To investigate the host response to (+)RNA virus-induced endomembrane disruption.
• To elucidate the role of endoplasmic reticulum (ER)-phagy in antiviral defense.
• To identify host factors that restrict (+)RNA virus replication.

Main Methods:

• Utilized beet black scorch virus (BBSV) in Nicotiana benthamiana as a model system.
• Investigated the interaction between BBSV protein p23 and ER-phagy receptor NbSec62.
• Analyzed the unfolded protein response (UPR) activation and its effect on ER-phagy and viral replication.

Main Results:

• BBSV infection induces ER-phagy, mediated by viral protein p23 interacting with NbSec62.
• A specific phenylalanine residue (F48) in p23 is crucial for NbSec62 interaction and ER-phagy.
• UPR activation promotes viral replication but also triggers NbSec62-mediated ER-phagy to suppress BBSV.
• NbSec62 acts as a restriction factor against other ER-replicating (+)RNA viruses like TMV and TuMV.

Conclusions:

• NbSec62 functions as a critical restriction factor against (+)RNA viruses by interacting with viral replication organelles.
• The UPR-ER-phagy signaling network plays a key role in balancing viral replication and ER homeostasis during infection.
• Understanding this network provides insights into plant antiviral defense strategies.