Potential roles of GRP78 in COVID-19 (IMAGE)

Osaka University

Potential roles of GRP78 in COVID-19

Caption

In older and obese diabetic patients①, hyperinsulinemia② causes cellular stress and induces the XBP-1-mediated overexpression of GRP78③ in adipose tissue, which promotes localization of GRP78 to the circulation④ and cell surface⑤, not only to endoplasmic reticulum (ER)⑥. GRP78 physically interacts with the SARS-CoV-2 spike protein, which may play a number of crucial roles in the viral lifecycle. The interaction of the spike protein with soluble and cell surface GRP78 may facilitate the SARS-CoV-2 binding to and infection of ACE2-expressing host cells. Soluble GRP78 bound to SARS-CoV-2 in the circulation could induce the systemic viral spread and infection. Binding of SARS-CoV-2 to cell surface GRP78 or related stimuli could activate the NF-κB or JNK/STAT3 transcriptional pathway and induce cellular inflammatory responses. SARS-CoV-2 potentially exploits ER-located GRP78 as a molecular chaperone to produce and assemble viral particles, which enables successful viral replication (brown virus indicates newly replicated SARS-CoV-2). The high expression of GRP78 in older and obese diabetic patients may contribute to the COVID-19 progression and severe outcomes.

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The American Diabetes Association

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