Differential role of sphingomyelin in influenza virus, rhinovirus and SARS-CoV-2 infection of Calu-3 cells

Abstract

Host cell lipids play a pivotal role in the pathogenesis of respiratory virus infection. However, a direct comparison of the lipidomic profile of influenza virus and rhinovirus infections is lacking. In this study, we first compared the lipid profile of influenza virus and rhinovirus infection in a bronchial epithelial cell line. Most lipid features were downregulated for both influenza virus and rhinovirus, especially for the sphingomyelin features. Pathway analysis showed that sphingolipid metabolism was the most perturbed pathway. Functional study showed that bacterial sphingomyelinase suppressed influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, but promoted rhinovirus replication. These findings suggest that sphingomyelin pathway can be a potential target for antiviral therapy, but should be carefully evaluated as it has opposite effects on different respiratory viruses. Furthermore, the differential effect of sphingomyelinase on rhinovirus and influenza virus may explain the interference between rhinovirus and influenza virus infection.

Machine learning identified distinct serum lipidomic signatures in hospitalized COVID-19-positive and COVID-19-negative patients

“…negative patients. These results agree with those reported in Calu-3 cells, where an increase in PC synthesis was observed when the cells were infected with SARS-CoV-2 [35]. Differences between the characteristics of the lipid groups studied can probably explain this discrepancy between different authors’ findings.…”

“…Several factors could influence plasma PC and LPC concentrations. For example, both are key components of cell membranes and lipoproteins, and low plasma levels of these compounds may be explained as resulting from liver impairment in patients with severe COVID-19, while their increase would suggest increased activity of phospholipase A2 [35]. Alterations in PC and LPC levels have been related to disease severity because of the role that these lipids play in the inflammatory response [36].…”

Machine learning and semi-targeted lipidomics identify distinct serum lipid signatures in hospitalized COVID-19-positive and COVID-19-negative patients

“…For example, both are key components of cell membranes and lipoproteins. Low plasma levels of these compounds may be explained as resulting from liver impairment in patients with severe COVID-19, while their increase would suggest increased activity of phospholipase A 2 [48] . Alterations in PC and LPC levels have been related to disease severity because of the roles that these lipids play in the inflammatory response [49] .…”

SARS-CoV2 Infection Alters Tryptophan Catabolism and Phospholipid Metabolism

“…Importantly, the levels of these phospholipids declined drastically even on recovery, thus pointing towards prolonged dysregulation in the serum phospholipids on COVID-19 infection. Taken together, our study shows that sphingolipid and phosphatidylcholine metabolism have important roles in regulating SARS-CoV2 infection that could develop as a target for therapeutic interventions for COVID-19 [9,25].…”