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人呼吸道合胞病毒氨基酸变异的计算机模拟分析:对免疫诊断的见解

In silico analysis of amino acid variation in human respiratory syncytial virus: insights into immunodiagnostics.

作者信息

Souza Claudemir, Zanchin Nilson It, Krieger Marco A, Ludwig Adriana

机构信息

Fundação Oswaldo Cruz-Fiocruz, Instituto Carlos Chagas, Laboratório de Genômica Funcional, Curitiba, PR, Brasil.

Instituto de Biologia Molecular do Paraná, Curitiba, PR, Brasil.

出版信息

Mem Inst Oswaldo Cruz. 2017 Oct;112(10):655-663. doi: 10.1590/0074-02760170013.

Abstract

BACKGROUND

The highly contagious nature of human respiratory syncytial virus (HRSV) and the gravity of its infection in newborns and vulnerable adults pose a serious public health problem. Thus, a rapid and sensitive diagnostic test for viral detection that can be implemented upon the first appearance of symptoms is needed. The genetic variation of the virus must be considered for immunodiagnostic purposes.

OBJECTIVES

To analyse HRSV genetic variation and discuss the possible consequences for capture immunoassay development.

METHODS

We performed a wide analysis of N, F and G protein variation based on the HRSV sequences currently available in the GenBank database. We also evaluated their similarity with homologous proteins from other viruses.

FINDINGS

The mean amino acid divergences for the N, F, and G proteins between HRSV-A and HRSV-B were determined to be approximately 4%, 10% and 47%, respectively. Due to their high conservation, assays based on the full-length N and F proteins may not distinguish HRSV from human metapneumovirus and other Mononegavirales viruses, and the full-length G protein would most likely produce false negative results due to its high divergence.

MAIN CONCLUSIONS

We have identified specific regions in each of these three proteins that have higher potential to produce specific results, and their combined utilisation should be considered for immunoassay development.

摘要

背景

人类呼吸道合胞病毒(HRSV)具有高度传染性,其在新生儿和易感成人中的感染严重性构成了严重的公共卫生问题。因此,需要一种在症状首次出现时即可实施的快速且灵敏的病毒检测诊断测试。出于免疫诊断目的,必须考虑该病毒的基因变异。

目的

分析HRSV基因变异并探讨其对捕获免疫测定法开发可能产生的影响。

方法

我们基于GenBank数据库中目前可用的HRSV序列,对N、F和G蛋白变异进行了广泛分析。我们还评估了它们与其他病毒同源蛋白的相似性。

研究结果

HRSV-A和HRSV-B之间N、F和G蛋白的平均氨基酸差异分别确定为约4%、10%和47%。由于其高度保守性,基于全长N和F蛋白的测定可能无法区分HRSV与人间质肺病毒及其他单股负链RNA病毒,而全长G蛋白因其高度差异很可能产生假阴性结果。

主要结论

我们已在这三种蛋白的每一种中鉴定出具有更高产生特异性结果潜力的特定区域,在免疫测定法开发中应考虑联合使用这些区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ca0/5607514/780ebc494d72/0074-0276-mioc-112-10-0655-gf01.jpg

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