Human embryonic lung fibroblasts treated with artesunate exhibit reduced rates of proliferation and human cytomegalovirus infection in vitro.

BACKGROUND: Cytomegalovirus (CMV) pneumonia is a major cause of death in immunosuppressed patients. Despite the effective treatment with ganciclovir (GCV) and other antiviral agents, the mortality rate remains between 30% to 50%. Recently, the anti-malarial drug artesunate (ART) wasfound to exhibit significant anti-viral activity. Here, we examined the effects of ART on human cytomegalovirus (HCMV) infection and human embryonic lung fibroblast (HELF) proliferation in vitro. METHODS: HELFs infected with the GFP-expressing Towne-BAC strain of HCMV were divided into three treatment groups: Group I, cells treated with ART for 1.5 h before HCMV inoculation; Group II, cells infected with HCMV that was pre-treated with ART for 1.5 h before HCMV inoculation; Group III, cells that were treated with ART at 1.5 h post-HCMV inoculation. GFP expression was observed daily by fluorescence microscopy, and the number of GFP-positive cells in each experimental group was recorded at 4-5 days post-infection. At 10 days post-infection, the viability of cells in each group was recorded. GCV treatment was used as a control. RESULTS: While no significant effects on cytotoxicity, cell viability, viral infection rates, or antiviral activity were observed upon treatment of Group I or II cells with GCV or low levels of ART, the ART-treated Group III population exhibited significantly reduced rates of infection at drug concentrations higher than 12.5 µM. Similarly, we observed a GCV concentration-dependent reduction in the viral infection rate in Group III cells. Notably, ART-treated, but not GCV-treated, cells also exhibited decreased proliferation. The 50% cytostatic concentrations (CC50) and the half maximal inhibitory concentrations (IC50) of ART and GCV were 54.382 µM and 12.679 µM, and 3.76 M and 14.479 µM, respectively. CONCLUSIONS: In addition to its robust antiviral activity, ART inhibits proliferation of HCMV-infected lung fibroblasts, making it a potential next-generation drug for CMV pneumonia treatment and for reducing fibroproliferation and fibrosis in these patients.

Myelin-associated glycoprotein inhibits the neuronal differentiation of neural progenitors.

Nogo-66, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein, possess axon growth-inhibiting properties by binding with the Nogo-66 receptor. Recent studies have shown that Nogo-66 inhibits neuronal differentiation of neural progenitor cells (NPCs) and the neurite outgrowth of the neurons differentiated from NPCs. However, the effects of MAG on the differentiation and proliferation of NPCs are unclear. We found that NPCs derived from the hippocampus of embryonic rats expressed Nogo-66 receptor and MAG-Fc, which mimics the function of MAG, inhibited the differentiation of NPCs into neurons but promoted differentiation of NPCs into astrocytes. Furthermore, MAG-Fc inhibited the neurite outgrowth of the neurons differentiated from NPCs. Our results suggest that MAG can inhibit the neuronal differentiation of NPCs.