The novel
coronavirus pandemic, whose first outbreak was reported in December 2019 in Wuhan,
China (COVID-19), is caused by the
severe acute respiratory syndrome coronavirus 2 (
SARS-CoV-2).
Tissue damage caused by the
virus leads to a strong
immune response and activation of
antigen-presenting cells, which can elicit
acute respiratory distress syndrome (ARDS) characterized by the rapid onset of widespread
inflammation, the so-called
cytokine storm. In many
viral infections the recruitment of
monocytes into the
lung and their differentiation to
dendritic cells (DCs) are seen as a response to the
viral infection. DCs are critical players in the development of the acute
lung inflammation that causes ARDS. Here we focus on the interaction of the ORF8
protein, a specific
SARS-CoV-2 open reading frame protein, with
dendritic cells (DCs). We show that ORF8 binds to
dendritic cells, causes a pre-maturation of differentiating DCs, and induces the
secretion of multiple pro-inflammatory
cytokines by these
cells. In addition, we identified
dendritic cell-specific
intercellular adhesion molecule-3-grabbing non-
integrin (DC-SIGN) as a possible interaction partner of ORF8 on
dendritic cells. Blockade of ORF8 signaling leads to reduced
production of
IL-1{beta},
IL-6, IL-12p70, TNF-, MCP-1 (CCL2), and
IL-10 by
dendritic cells.
Analysis of
patient sera with high anti-ORF8 antibody titers showed that there was nearly no neutralization of the ORF8
protein and its function. Therefore, a
neutralizing antibody that has the capacity of blocking the
cytokine and
chemokine response mediated by ORF8
protein might be an essential and novel additional step in the
therapy of severe
SARS-CoV-2 cases.