人偏肺病毒 1 融合蛋白基因的分子进化分析。

Molecular evolutionary analyses of the fusion protein gene in human respirovirus 1.

机构信息

Iwate Prefectural Research Institute for Environmental Science and Public Health, Morioka-shi, Iwate 020-0857, Japan.

Department of Health Science, Gunma Paz University Graduate School of Health Sciences, Takasaki-shi, Gunma 370-0006, Japan.

出版信息

Virus Res. 2023 Aug;333:199142. doi: 10.1016/j.virusres.2023.199142. Epub 2023 Jun 9.

Abstract

Few evolutionary studies of the human respiratory virus (HRV) have been conducted, but most of them have focused on HRV3. In this study, the full-length fusion (F) genes in HRV1 strains collected from various countries were subjected to time-scaled phylogenetic, genome population size, and selective pressure analyses. Antigenicity analysis was performed on the F protein. The time-scaled phylogenetic tree using the Bayesian Markov Chain Monte Carlo method estimated that the common ancestor of the HRV1 F gene diverged in 1957 and eventually formed three lineages. Phylodynamic analyses showed that the genome population size of the F gene has doubled over approximately 80 years. Phylogenetic distances between the strains were short (< 0.02). No positive selection sites were detected for the F protein, whereas many negative selection sites were identified. Almost all conformational epitopes of the F protein, except one in each monomer, did not correspond to the neutralising antibody (NT-Ab) binding sites. These results suggest that the HRV1 F gene has constantly evolved over many years, infecting humans, while the gene may be relatively conserved. Mismatches between computationally predicted epitopes and NT-Ab binding sites may be partially responsible for HRV1 reinfection and other viruses such as HRV3 and respiratory syncytial virus.

摘要

对人类呼吸道病毒(HRV)的进化研究较少,但大多数研究都集中在 HRV3 上。本研究对来自不同国家的 HRV1 株全长融合(F)基因进行了时间尺度的系统发育、基因组种群大小和选择压力分析。对 F 蛋白进行了抗原性分析。贝叶斯马尔可夫链蒙特卡罗方法的时间尺度系统发育树估计,HRV1 F 基因的共同祖先在 1957 年分化,并最终形成三个谱系。系统发育动力学分析表明,F 基因的基因组种群大小在大约 80 年内增加了一倍。株间的系统发育距离很短(<0.02)。未检测到 F 蛋白的阳性选择位点,但鉴定了许多负选择位点。F 蛋白的几乎所有构象表位(每个单体中的一个除外)都与中和抗体(NT-Ab)结合位点不对应。这些结果表明,HRV1 F 基因在多年来不断进化,感染人类,而该基因可能相对保守。计算预测的表位与 NT-Ab 结合位点之间的不匹配可能部分导致 HRV1 的再感染以及其他病毒(如 HRV3 和呼吸道合胞病毒)。

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