SARS-CoV-2 Infection Induces HMGB1 Secretion Through Post-Translational Modification and PANoptosis
- Author:
Man Sup KWAK
1
;
Seoyeon CHOI
;
Jiseon KIM
;
Hoojung LEE
;
In Ho PARK
;
Jooyeon OH
;
Duong Ngoc MAI
;
Nam-Hyuk CHO
;
Ki Taek NAM
;
Jeon-Soo SHIN
Author Information
- Publication Type:Original Article
- From:Immune Network 2023;23(3):e26-
- CountryRepublic of Korea
- Language:English
- Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality.High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.
