Coronavirus but not influenza virus infection induces the expression of both cellular and soluble urokinase plasminogen activator receptor

ABSTRACT

Background: Urokinase plasminogen activator receptor (uPAR/PLAUR) is a cell surface receptor on monocytes and macrophages (MO/MPs), which when cleaved, forms soluble uPAR (suPAR). Previous work has shown that uPAR is differentially induced in MO/MPs after coronavirus (CoV) infection and contributes to hyperfibrinolysis. In contrast to cellular uPAR's fibrinolytic function (implicated in CoV-induced coagulopathy), suPAR is a MP chemotactic factor implicated in perpetuating tissue injury after CoV infection. However, it is unclear if induced levels of cellular uPAR correlate with the elevated levels of suPAR after CoV infection and how suPAR expression is regulated after influenza virus (IAV) infection. Method(s) Published scRNA sequencing data (GSE149689) of PBMCs from patients (COVID-positive and IAV-positive) and healthy controls was analyzed. In vitro, we performed infections of immortalized murine MPs (RAW264.7) with the CoVs MHVA59 or MHV1, or the IAV (A/PR/8/34;H1N1) at the indicated MOI for 24 hours. uPAR and urokinase levels were measured by ELISA. Urokinase activity of conditioned media was measured using a commercially available colorimetric assay. Result(s) ScRNA analysis revealed differential expression of PLAUR in MOs from COVID and IAV-positive relative to healthy controls, with the highest PLAUR expression in COVID-positive samples (Fig. A-B). Infection of RAW264.7 cells with CoV and IAV induced cellular uPAR expression, but only CoV infection induced suPAR expression (Fig. C). In contrast to uPAR, the expression of both cellular and soluble urokinase levels was induced after infection with either CoVs or IAV (Fig. D). Finally, induction of urokinase activity of conditioned media after viral stimulation was observed after infection with either CoVs or IAV (Fig. E). Conclusion(s) CoV but not IAV infection induces the expression of both cellular and soluble uPAR in MO/MPs. Both CoV and IAV induce the expression of cellular and soluble urokinase, and urokinase activity. Understanding this virus specific effect on uPAR/suPAR in innate immune cells may reveal the pathogenesis of virus-associated coagulopathy and tissue injury.