Using dsRNA: nanoparticles to determine a link between type I interferons, ACE2 and susceptibility to coronaviruses similar to COVID-19

Dewitte-Orr, Stephanie | $50,000

Ontario Wilfrid Laurier University 2020 NSERC Alliance COVID-19 Grant

Viruses are obligate intracellular pathogens that require a host cell in order to replicate. The novel coronavirus, SARS-CoV-2, that emerged late 2019 in Wuhan China is a virus that primarily infects the airway epithelium. It is becoming more evident; however, that airway epithelial cells are not the only cell type susceptible to SARS-CoV-2 infection. Cells of the gastrointestinal tract, specifically gastric, duodenal and rectum glandular epithelial cells, as well as kidney tubule epithelial cells are also capable of supporting SARS-CoV-2 replication. One of the principle ways cells protect themselves from virus infections is by producing type I interferons (IFNs). A recent paper has suggested that the surface receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is induced by IFNs. This suggests that the host’s innate immune response may be making an individual more susceptible to the virus. The current proposal aims to use a potent inducer of IFNs, pIC:PhG, produced by Glysantis, Inc, to study the linkages between IFN, ACE2 and coronavirus susceptibility. PIC:PhG consists of two components; the innate immune stimulant, poly inosinic: poly cytidylic acid (pIC) bound to a phytoglycogen nanoparticle (PhG) and is capable of inducing significantly more IFNs than pIC alone. The three objectives of this study will be: (1) to test the effect of pIC:PhG in primary human airway (HAE), renal tubule (RPTEC) and duodenum epithelial cells (HDuEpC) to confirm its ability to induce IFNs in these cell types, (2) to test whether pIC:PhG-induced IFNs induce ACE2 in these cell types and (3) to correlate increased ACE2 expression with increased susceptibility to human coronavirus infection and replication. This work will provide Glysantis with fundamental understanding of their nanoparticle and its ability to induce IFNs, and will provide the scientific community with a better understanding of the influence of the innate immune response on coronavirus susceptibility.

With funding from the Government of Canada

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