Immune Netw.  2023 Jun;23(3):e26. 10.4110/in.2023.23.e26.

SARS-CoV-2 Infection Induces HMGB1 Secretion Through Post-Translational Modification and PANoptosis

• Kwak MS
• Choi S
• Kim J
• Lee H
• Park IH
• Oh J
• Mai DN
• Cho NH
• Nam KT
• Shin JS

• KMID: 2544690
• DOI: http://doi.org/10.4110/in.2023.23.e26

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.

Keyword

HMGB1 protein; Severe acute respiratory syndrome coronavirus 2; Post-translational modification; PANoptosis