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.

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Ncbi/Checkpoint

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002178 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Checkpoint/biblio.hfd -nk 002178 | SxmlIndent | more

{{Explor lien
   |wiki=    Sante
   |area=    SrasV1
   |flux=    Ncbi
   |étape=   Checkpoint
   |type=    RBID
   |clé=     pubmed:20667598
   |texte=   SARS spike protein induces phenotypic conversion of human B cells to macrophage-like cells.
}}

HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Checkpoint/RBID.i   -Sk "pubmed:20667598" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Checkpoint/biblio.hfd   \
       | NlmPubMed2Wicri -a SrasV1