tailieunhanh - Báo cáo y học: "Nipah virus infection and glycoprotein targeting in endothelial cells"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Nipah virus infection and glycoprotein targeting in endothelial cells | Erbar and Maisner Virology Journal 2010 7 305 http content 7 1 305 VIROLOGY JOURNAL RESEARCH Open Access Nipah virus infection and glycoprotein targeting in endothelial cells Stephanie Erbar Andrea Maisner Abstract Background The highly pathogenic Nipah virus NiV causes fatal respiratory and brain infections in animals and humans. The major hallmark of the infection is a systemic endothelial infection predominantly in the CNS. Infection of brain endothelial cells allows the virus to overcome the blood-brain-barrier BBB and to subsequently infect the brain parenchyma. However the mechanisms of NiV replication in endothelial cells are poorly elucidated. We have shown recently that the bipolar or basolateral expression of the NiV surface glycoproteins F and G in polarized epithelial cell layers is involved in lateral virus spread via cell-to-cell fusion and that correct sorting depends on tyrosine-dependent targeting signals in the cytoplasmic tails of the glycoproteins. Since endothelial cells share many characteristics with epithelial cells in terms of polarization and protein sorting we wanted to elucidate the role of the NiV glycoprotein targeting signals in endothelial cells. Results As observed in vivo NiV infection of endothelial cells induced syncytia formation. The further finding that infection increased the transendothelial permeability supports the idea of spread of infection via cell-to-cell fusion and endothelial cell damage as a mechanism to overcome the BBB. We then revealed that both glycoproteins are expressed at lateral cell junctions bipolar not only in NiV-infected primary endothelial cells but also upon stable expression in immortalized endothelial cells. Interestingly mutation of tyrosines 525 and 542 543 in the cytoplasmic tail of the F protein led to an apical redistribution of the protein in endothelial cells whereas tyrosine mutations in the G protein had no effect at all. This fully contrasts the previous results in .