Deng Hongkui

Neutralizing Antibodies in Patients with Severe Acute Respiratory Syndrome-Associated Coronavirus Infection

Abstract Background. Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is the principal etiologic agent of SARS. We analyzed serum samples obtained from 623 patients with SARS in Beijing, to determine whether infection with SARS-CoV can elicit neutralizing antibodies (NAbs). Methods. We developed a highly sensitive and safe neutralization assay using the SARS-CoV pseudotyped virus and used this assay to determine the titers of the NAbs in serum samples from patients with SARS. Results. We found that 85.9% of serum samples contained NAbs against SARS-CoV and that most of the NAb activities could be attributed to immunoglobulin G. The NAbs became detectable first at 5–10 days after the onset of symptoms, and their levels peaked at 20–30 days and then were sustained for >150 days. The serum samples could neutralize the pseudotype particles bearing the spike glycoproteins from different SARS-CoV strains, suggesting that the NAbs to SARS-CoV were broadly reactive. Conclusions. NAbs to SARS-CoV are broadly elicited in patients with SARS and, according to their kinetics, may correlate with viral load during the early stages of the disease. These results suggest that it is possible to develop effective vaccines against SARS and that NAbs provide a potential strategy for treating patients with SARS.

Hypoxia Enhances the Differentiation of Hemogenic Endothelial Cells from Human Embryonic Stem Cells through Up-regulating Wnt5a Signal

Hypoxia plays important roles in embryonic vasculogenesis, hematopoiesis and has been applied in embryonic stem (ES) cell differentiation towards endothelial and hematopoietic cells. However, the precise role of hypoxia and its underlying mechanisms on the hematopoietic differentiation remains unclear. In this study, we found that hypoxia enhanced the generation of CD31 + TIE 2+ hemato-vascular progenitor cells from human ES-derived mesoderm cells, and followed by the gene expression of definitive hematopoietic genes after two days. Importantly, we found that hypoxia functioned on the hemato-vascular progenitor differentiation by stimulating the enhanced secretion of Wnt5a, while Wnt5a disrupted with shRNA inhibited the generation of hemato-vascular progenitor cells. Wnt5a added in normoxia promoted the generation of hemato-vascular progenitor cells and this effect is similar to that generated by hypoxia to enhance the generation of hemato-vascular progenitor cells. In conclusion, our study is the first to identify that hypoxia enhanced the generation of hemato-vascular progenitor cells from human ES cell-derived mesoderm through up-regulating Wnt5a signal. This finding provides new clues for studying the mechanism of committed differentiation of hemogenic endothelium and HPC/HSCs from human ES cells.