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血凝素假型慢病毒颗粒:一种新型禽H5N1流感血清诊断方法的特性研究

Hemagglutinin pseudotyped lentiviral particles: characterization of a new method for avian H5N1 influenza sero-diagnosis.

作者信息

Nefkens Isabelle, Garcia Jean-Michel, Ling Chu Shui, Lagarde Nadège, Nicholls John, Tang Dong Jiang, Peiris Malik, Buchy Philippe, Altmeyer Ralf

机构信息

HKU-Pasteur Research Center, Hong Kong, SAR China.

出版信息

J Clin Virol. 2007 May;39(1):27-33. doi: 10.1016/j.jcv.2007.02.005. Epub 2007 Apr 3.

Abstract

BACKGROUND

Highly pathogenic avian influenza (HPAI) H5N1 has spread globally in birds and infected over 270 humans with an apparently high mortality rate. Serologic studies to determine the extent of asymptomatic H5N1 infection in humans and other mammals and to investigate the immunogenicity of current H5N1 vaccine candidates have been hampered by the biosafety requirements needed for H5N1 micro-neutralization tests.

OBJECTIVE

Development of a serodiagnostic tool for highly pathogenic influenza that reproduces H5N1 biology but can be used with less biohazard.

STUDY DESIGN

We have generated and evaluated H5 hemagglutinin pseudotyped lentiviral particles encoding the luciferase reporter (H5pp).

RESULTS

H5pp entry into target cells depends on alpha2-3 cell surface sialic acids and requires low pH for membrane fusion. H5pp infectivity is specifically neutralized by sera from patients and animals infected with H5N1 and correlates well with conventional microneutralization test.

CONCLUSIONS

H5pp reproduce H5N1 influenza virus entry into target cells and potentially provides a high-throughput and safe method for sero-epidemiology.

摘要

背景

高致病性禽流感(HPAI)H5N1已在全球禽类中传播,并感染了270多名人类,死亡率明显很高。血清学研究旨在确定人类和其他哺乳动物中无症状H5N1感染的程度,并调查当前H5N1候选疫苗的免疫原性,但受到H5N1微量中和试验所需生物安全要求的阻碍。

目的

开发一种用于高致病性流感的血清诊断工具,该工具能重现H5N1生物学特性,但生物危害较小。

研究设计

我们构建并评估了编码荧光素酶报告基因的H5血凝素假型慢病毒颗粒(H5pp)。

结果

H5pp进入靶细胞依赖于α2-3细胞表面唾液酸,且膜融合需要低pH值。H5pp感染性可被感染H5N1的患者和动物血清特异性中和,且与传统微量中和试验相关性良好。

结论

H5pp重现了H5N1流感病毒进入靶细胞的过程,并可能为血清流行病学提供一种高通量且安全的方法。

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