SARS spike protein induces phenotypic conversion of human B cells to macrophage-like cells

Abstract

Massive aggregations of macrophages are frequently detected in afflicted lungs of patients with severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In vitro, ectopic expression of transcription factors, in particular CCAAT/enhancer-binding protein alpha (C/EBPα) and C/EBPβ, can convert B cells into functional macrophages. However, little is known about the specific ligands responsible for such phenotype conversion. Here, we investigated whether spike protein of SARS-CoV can act as a ligand to trigger the conversion of B cells to macrophages. We transduced SARS-CoV spike protein-displayed recombinant baculovirus (SSDRB), vAtEpGS688, into peripheral B cells and B lymphoma cells. Cell surface expression of CD19 or Mac-1 (CD11b) was determined by flow cytometry. SSDRB-mediated changes in gene expression profiles of B lymphoma cells were analyzed by microarray. In this report, we showed that spike protein of SARS virus could induce phenotypic conversion of human B cells, either from peripheral blood or B lymphoma cells, to macrophage-like cells that were steadily losing the B-cell marker CD19 and in turn expressing the macrophage-specific marker Mac-1. Furthermore, we found that SSDRB enhanced the expression of CD86, hypoxia-inducible factor-1α (HIF1α), suppressor of cytokine signaling (SOCS or STAT-induced STAT inhibitor)-3, C/EBPβ, insulin-like growth factor-binding protein 3 (IGFBP3), Krüpple-like factor (KLF)-5, and CD54, without marked influence on C/EBPα or PU.1 expression in transduced cells. Prolonged exposure to hypoxia could also induce macrophage-like conversion of B cells. These macrophage-like cells were defective in phagocytosis of red fluorescent beads. In conclusion, our results suggest that conversion of B cells to macrophage-like cells, similar to a pathophysiological response, could be mediated by a devastating viral ligand, in particular spike protein of SARS virus, or in combination with severe local hypoxia, which is a condition often observed in afflicted lungs of SARS patients.

Pulmonary macrophages: key players in the innate defence of the airways

“…Infection with the severe acute respiratory syndrome (SARS) coronavirus, the causal agent of SARS, results in a significant accumulation of enlarged M2 macrophages in the lung 32. Spike (S) protein, a major structural component of SARS, induces the conversion of B cells into cells that resemble macrophages, when displayed on recombinant baculovirus 33. Dosch et al 34 showed that secreted S protein could activate blood monocytes via TLR2.…”

Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge

“…Monocytes/macrophages have also been implicated in SARS-CoV disease pathogenesis (8,38). In SARS-CoV patients, infiltrating monocytes/macrophages have been shown to persist long after the virus has been eradicated from the lung, and the excessive accumulation of these cells is a prominent pathological feature in most SARS-CoV autopsy cases (9).…”

Abnormal Processing of Autophagosomes in Transformed B Lymphocytes from SCARB2-Deficient Subjects

“…The origin of the structures identified in the present study is not likely to be phagosomes, because B lymphocytes are not generally capable of phagocytosis. 18 In addition, the cells were not challenged with an external pathogen, and phagocytic activity was not observed by electron microscopy.…”