The Accessory Protein ORF3a Hijacks CLCC1 Chloride Channel to Cause ER Dysfunction in Beta-coronavirus Pathogenesis DOI Creative Commons
Liang Guo, Baoying Huang, Hanzhi Yu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract The endoplasmic reticulum (ER) homeostasis is crucial for host cells and influenced by beta-coronaviruses upon invasion. However, the mechanisms which viral proteins interact with ER-resident factors to modulate ER functions morphology remain poorly understood. accessory protein ORF3a of SARS-CoV-2 plays a pivotal role in pathogenesis modulating immune responses. ER-localized chloride channel CLCC1 has been identified as strong interaction partner ORF3a, yet consequences this are not fully elucidated. Here, we demonstrate that interacts ion homeostasis, including increased luminal [Cl−], [K+], decreased [Ca2+], trigger unfolded ORF3a-CLCC1 linked phagy nucleophagy, monitored newly developed ratiometric reporters. Mechanistically, induces formation endogenous puncta, while overexpression attenuates ORF3a-associated toxicity sequestering within ER. Furthermore, conservation across suggests it potential therapeutic target uncovers ORF3a-mediated phenotypes spatiotemporally. In addition, expression mouse brains causes stress, phagy, endomembrane reorganization, shedding light on neurological manifestations long-term effects observed COVID-19 patients.

Language: Английский

The Accessory Protein ORF3a Hijacks CLCC1 Chloride Channel to Cause ER Dysfunction in Beta-coronavirus Pathogenesis DOI Creative Commons
Liang Guo, Baoying Huang, Hanzhi Yu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract The endoplasmic reticulum (ER) homeostasis is crucial for host cells and influenced by beta-coronaviruses upon invasion. However, the mechanisms which viral proteins interact with ER-resident factors to modulate ER functions morphology remain poorly understood. accessory protein ORF3a of SARS-CoV-2 plays a pivotal role in pathogenesis modulating immune responses. ER-localized chloride channel CLCC1 has been identified as strong interaction partner ORF3a, yet consequences this are not fully elucidated. Here, we demonstrate that interacts ion homeostasis, including increased luminal [Cl−], [K+], decreased [Ca2+], trigger unfolded ORF3a-CLCC1 linked phagy nucleophagy, monitored newly developed ratiometric reporters. Mechanistically, induces formation endogenous puncta, while overexpression attenuates ORF3a-associated toxicity sequestering within ER. Furthermore, conservation across suggests it potential therapeutic target uncovers ORF3a-mediated phenotypes spatiotemporally. In addition, expression mouse brains causes stress, phagy, endomembrane reorganization, shedding light on neurological manifestations long-term effects observed COVID-19 patients.

Language: Английский

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