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骆驼痘病毒血凝素基因的序列分析显示缺失导致移码:骆驼痘病毒中不同聚类的循环。

Sequence analysis of haemagglutinin gene of camelpox viruses shows deletion leading to frameshift: Circulation of diverse clusters among camelpox viruses.

机构信息

Division of Virology, ICAR-Indian Veterinary Research Institute, Mukteswar, Uttarakhand, India.

ICAR-National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru, Karnataka, India.

出版信息

Transbound Emerg Dis. 2018 Dec;65(6):1920-1934. doi: 10.1111/tbed.12973. Epub 2018 Aug 13.

Abstract

Orthopoxviruses (OPVs) have broad host range infecting a variety of species along with gene-specific determinants. Several genes including haemagglutinin (HA) are used for differentiation of OPVs. Among poxviruses, OPVs are sole members encoding HA protein as part of extracellular enveloped virion membrane. Camelpox virus (CMLV) causes an important contagious disease affecting mainly young camels, endemic to Indian subcontinent, Africa and the Middle East. This study describes the sequence features and phylogenetic analysis of HA gene (homologue of VACV A56R) of Indian CMLV isolates. Comparative analysis of CMLV HA gene revealed conserved nature within CMLVs but considerable variability was observed between various species of OPVs. Most Indian CMLV isolates showed 99.5%-100% and 96.3%-100% identity, at nucleotide (nt) and amino acid (aa) levels respectively, among themselves and with CMLV-M96 strain. Importantly, Indian CMLV strains along with CMLV-M96 showed deletion of seven nucleotides resulting in frameshift mutation at C-terminus of HA protein. Phylogenetic analysis displayed distinct clustering among CMLVs which might point to the circulation of diverse CMLV strains in nature. Despite different host specificity of OPVs, comparative sequence analysis of HA protein showed highly conserved N-terminal Ig V-set functional domain with tandem repeats. Understanding of molecular diversity of CMLVs and structural domains of HA protein will help in the elucidation of molecular mechanisms for immune evasion and design of novel antivirals for OPVs.

摘要

正痘病毒(OPV)宿主范围广泛,可感染多种物种,并具有特定的基因决定簇。包括血凝素(HA)在内的多个基因被用于 OPV 的分化。在痘病毒中,OPV 是唯一编码 HA 蛋白的成员,HA 蛋白是细胞外包膜病毒膜的一部分。骆驼痘病毒(CMLV)引起一种重要的传染病,主要影响印度次大陆、非洲和中东地区的幼骆驼。本研究描述了印度 CMLV 分离株 HA 基因(与 VACV A56R 同源)的序列特征和系统发育分析。CMLV HA 基因的比较分析表明,CMLV 之间具有保守性,但各种 OPV 之间存在相当大的变异性。大多数印度 CMLV 分离株在核苷酸(nt)和氨基酸(aa)水平上彼此之间以及与 CMLV-M96 株的同源性分别为 99.5%-100%和 96.3%-100%。重要的是,印度 CMLV 株与 CMLV-M96 株一样,在 HA 蛋白的 C 末端发生了七个核苷酸的缺失,导致移码突变。系统发育分析显示 CMLV 之间存在明显的聚类,这可能表明自然界中存在多种 CMLV 株的循环。尽管 OPV 的宿主特异性不同,但 HA 蛋白的比较序列分析显示,其具有高度保守的 N 端 Ig V 集功能域和串联重复。对 CMLV 的分子多样性和 HA 蛋白结构域的理解将有助于阐明免疫逃逸的分子机制,并为 OPV 设计新型抗病毒药物。

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