tailieunhanh - Báo cáo y học: "A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System | Khetawat and Broder Virology Journal 2010 7 312 http content 7 1 312 VIROLOGY JOURNAL RESEARCH Open Access A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System Dimple Khetawat Christopher C Broder Abstract Background Hendra virus HeV and Nipah virus NiV are newly emerged zoonotic paramyxoviruses discovered during outbreaks in Queensland Australia in 1994 and peninsular Malaysia in 1998 9 respectively and classified within the new Henipavirus genus. Both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals and repeated outbreaks continue to occur. Extensive laboratory studies on the host cell infection stage of HeV and NiV and the roles of their envelope glycoproteins have been hampered by their highly pathogenic nature and restriction to biosafety level-4 BSL-4 containment. To circumvent this problem we have developed a henipavirus envelope glycoprotein pseudotyped lentivirus assay system using either a luciferase gene or green fluorescent protein GFP gene encoding human immunodeficiency virus type-1 HIV-1 genome in conjunction with the HeV and NiV fusion F and attachment G glycoproteins. Results Functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity of the assay was confirmed by the lack of reporter-gene signals when particles bearing either only the F or only G glycoprotein were prepared and assayed. Virus entry could be specifically blocked when infection was carried out in the presence of a fusion inhibiting C-terminal heptad HR-2 peptide a well-characterized cross-reactive neutralizing human mAb specific for the henipavirus G glycoprotein and soluble ephrinB2 and B3 receptors. In addition the utility of the assay was also demonstrated by an .