Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infection

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a pandemic threat that has been declared a public health emergency of international concern, whereas the effects of cellular microenvironment in the pathogenesis of SARS-CoV-2 are poorly understood. The detailed message of intracellular/lysosome pH was rarely concerned in SARS-CoV-2 infection, which was crucial for the cleavage of SARS-CoV-2 spike (S) protein. Calprotectin, an endogenous danger signal to activate inflammatory response, was vital for the proceeding of COVID-19. We found that the expressions of both vacuolar-ATPase (V-ATPase) and calprotectin (S100A8/S100A9) increased in SARS-CoV-2 infection, by analyzing single-cell RNA sequencing (bronchoalveolar lavage fluid), bulk-RNA sequencing (A549, lung tissue, NHBE), and proteomics (lung tissue), respectively. Furtherly, our wet experiments of flow cytometry and fluorescent assay identified that the intracellular and lysosome pH value was decreased after SARS-CoV-2 S plasmid transfection in A549 cells. Meanwhile, the enhancement of V-ATPase and calprotectin was verified by our real-time polymerase chain reaction and western blot experiment. Collectively, these data suggested that S protein increased V-ATPase in SARS-CoV-2 infection, which provided a microenvironment easier for the cleavage of S protein, and inflammatory cells were apt to be activated by the enhancement of calprotectin in respiratory epithelium. The comprehensive information on profiles of V-ATPase and calprotectin will make clearer about the involvement of cellular microenvironment in the pathogenesis of SARS-CoV-2, and provide a promising approach to combat COVID-19.

Plasma Proteomics Unveil Novel Immune Signatures and Biomarkers upon SARS-CoV-2 Infection

“…ATP6V1 was upregulated in patients with antibody generation. This protein acidifies cellular compartments as well as the extracellular environment, which was previously found upregulated in SARS-CoV-2-infected cells [ 39 ]. Interestingly, it has been reported that an acidic pH environment facilitates SARS-CoV-2 infection [ 40 ].…”

Pathways in the brain, heart and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: anin silicostudy hinting cancer incidence

“…ATP6V0D1 was observed to be upregulated in A549 cells transfected with SARS-CoV-2 S plasmid and intracellular/lysosomal pH was observed to be decreased. 50 TCTN2, another regulated protein is shown to be associated with osteoarthritis. 51 PHLDA3 knock down is observed to be negatively affecting colony forming efficiency of MM468 cells expressing myr-Akt and high frequency of chromosome loss at PHLDA3 locus is also reported in large cell neuroendocrine carcinoma (LCNEC).…”

“…SARS-CoV-2 were shown to be increasing the expression of V-ATPase. 50 Pathway involving other hub genes TGFB1, TGFBR2, and LGALS3 was dendritic cell differentiation. Further analysis of pathways involving heart hub genes RAB7A, ATPV0D1, and LAMP2 were associated with phagosome related processes.…”

Transcriptional Profiles Analysis of COVID-19 and Malaria Patients Reveals Potential Biomarkers in Children

“…This observation is in line with a previous report which showed high expression of SERINC2 gene in COVID-19 patients [67] (Table 5). The ATP6V0C (ATPase H+ Transporting V0 Subunit C) is a component of V-ATPase (vacuolar ATPase) which inhibits lysosomal acidification mechanism by blocking the passage of H + via lysosomal membrane [68] and it has been found that S protein of SARS-CoV-2 induces the higher expression of V-ATPase within COVID-19 patients [69].…”