登革病毒基因组结构蛋白中的新型突变

Novel mutations in structural proteins of dengue virus genomes.

作者信息

Mushtaq Saira, Khan Malik Ihsan Ullah, Khan Muhammad Tahir, Lodhi Madeeha Shahzad, Wei Dong Qing

机构信息

Institute of Molecular Biology and Biotechnology, The University of Lahore, KM Defence Road, Postal code: 5881, Lahore, Pakistan.

Institute of Molecular Biology and Biotechnology, The University of Lahore, KM Defence Road, Postal code: 5881, Lahore, Pakistan; Zhongjing Research and Industrialization Institute of Chinese Medicine, Zhongguancun Scientific Park, Meixi, Nanyang, Henan 473006, PR China.

出版信息

J Infect Public Health. 2023 Dec;16(12):1971-1981. doi: 10.1016/j.jiph.2023.10.005. Epub 2023 Oct 5.

DOI:10.1016/j.jiph.2023.10.005

PMID:37879150

Abstract

BACKGROUND

Genomic characterization of the dengue virus (DENV) is useful for understanding its molecular evolution, transmission, pathogenicity and infectivity. The DENV genomic RNA encodes three structural proteins, capsid (C) envelope (E) and membrane (M) proteins mediating viral entry and assembly during host infection. The current study aims to explore the DENV serotypes and mutations in the E and M proteins.

METHODS

Twenty-three samples of DENV-positive patients were processed and selected for whole genome sequencing (WGS) from the Punjab Province of Pakistan.

RESULTS

Among the 23 WGS, 19 samples showed numerous mutations (BioProject ID PRJNA943555). DENV1 and DENV2 are the most prevalent serotypes. A total of 179 mutations were detected in the E protein, in which K203E, T88A, I114L, and I293T are novel. The I270L, T272A, S273L, and T277A were found in the "kl" β-hairpin (aa 270-279). The M protein harbors 74 mutations, of which 24 were novel. Three prominent complementary regions in the prM and E protein complex formations include R6, E46, D47, D63, and D65 on 'pr' peptide, and E84, K64, and H244, K247 on E, remain conserved except R6C. To our knowledge, it is the first comprehensive study of mutations in structural proteins.

CONCLUSION

Genomic epidemiology is critical for analyzing emerging mutations and designing new policies therapeutic efforts for future outbreaks.

摘要

背景

登革病毒（DENV）的基因组特征有助于理解其分子进化、传播、致病性和传染性。DENV基因组RNA编码三种结构蛋白，即衣壳（C）蛋白、包膜（E）蛋白和膜（M）蛋白，它们在宿主感染过程中介导病毒进入和组装。本研究旨在探索DENV血清型以及E和M蛋白中的突变情况。

方法

对来自巴基斯坦旁遮普省的23份DENV阳性患者样本进行处理并选择用于全基因组测序（WGS）。

结果

在23个WGS样本中，有19个样本显示出大量突变（生物项目编号PRJNA943555）。DENV1和DENV2是最常见的血清型。在E蛋白中总共检测到179个突变，其中K203E、T88A、I114L和I293T是新发现的。在“kl”β-发夹结构（氨基酸270 - 279）中发现了I270L、T272A、S273L和T277A。M蛋白含有74个突变，其中24个是新发现的。在prM和E蛋白复合物形成过程中的三个突出互补区域包括“pr”肽上的R6、E46、D47、D63和D65，以及E上的E84、K64和H244、K247，除了R6C外均保持保守。据我们所知，这是对结构蛋白突变的首次全面研究。