Scarborough Jessica A, Paul John R, Spencer Juliet V
Department of Biology, University of San Francisco, Harney Science Center, 2130 Fulton Street, San Francisco, CA 94117, USA.
Department of Biology, University of San Francisco, Harney Science Center, 2130 Fulton Street, San Francisco, CA 94117, USA.
Infect Genet Evol. 2017 Jul;51:46-53. doi: 10.1016/j.meegid.2017.03.013. Epub 2017 Mar 14.
Human cytomegalovirus (HCMV) is a widespread pathogen that is particularly skillful at evading immune detection and defense mechanisms, largely due to extensive co-evolution with its host. One aspect of this co-evolution involves the acquisition of virally encoded G protein-coupled receptors (GPCRs) with homology to the chemokine receptor family. GPCRs are the largest family of cell surface proteins, found in organisms from yeast to humans, and they regulate a variety of cellular processes including development, sensory perception, and immune cell trafficking. The US27 and US28 genes are encoded by human and primate CMVs, but homologs are not found in the genomes of viruses infecting rodents or other species. Phylogenetic analysis was used to investigate the US27 and US28 genes, which are adjacent in the unique short (US) region of the HCMV genome, and their relationship to one another and to human chemokine receptor genes. The results indicate that both US27 and US28 share the same common ancestor with human chemokine receptor CX3CR1, suggesting that a single host gene was captured and a subsequent viral gene duplication event occurred. The US28 gene product (pUS28) has maintained the function of the ancestral gene and has the ability to bind and signal in response to CX3CL1/fractalkine, the natural ligand for CX3CR1. In contrast, pUS27 does not bind to any known chemokine ligand, and the sequence has diverged significantly, highlighted by the fact that pUS27 currently exhibits greater sequence similarity to human CCR1. While the evolutionary advantage of the gene duplication and neofunctionalization event remains unclear, the US27 and US28 genes are highly conserved among different HCMV strains and retained even in laboratory strains that have lost many virulence genes, suggesting that US27 and US28 have each evolved distinct, important functions during virus infection.
人巨细胞病毒（HCMV）是一种广泛传播的病原体，尤其擅长逃避免疫检测和防御机制，这主要归因于它与宿主的长期共同进化。这种共同进化的一个方面涉及获得与趋化因子受体家族具有同源性的病毒编码G蛋白偶联受体（GPCR）。GPCR是细胞表面蛋白中最大的家族，存在于从酵母到人类的生物体中，它们调节多种细胞过程，包括发育、感官知觉和免疫细胞运输。US27和US28基因由人类和灵长类动物的巨细胞病毒编码，但在感染啮齿动物或其他物种的病毒基因组中未发现同源物。系统发育分析用于研究HCMV基因组独特短区域（US）中相邻的US27和US28基因，以及它们彼此之间以及与人类趋化因子受体基因的关系。结果表明，US27和US28与人类趋化因子受体CX3CR1拥有相同的共同祖先，这表明一个单一的宿主基因被捕获，随后发生了病毒基因复制事件。US28基因产物（pUS28）保留了祖先基因的功能，并且具有结合CX3CL1/趋化因子并对其作出信号反应的能力，CX3CL1/趋化因子是CX3CR1的天然配体。相比之下，pUS27不与任何已知的趋化因子配体结合，并且序列已经发生了显著分化，这一点突出表现在pUS27目前与人类CCR1表现出更高的序列相似性。虽然基因复制和新功能化事件的进化优势尚不清楚，但US27和US28基因在不同的HCMV毒株中高度保守，甚至在已经失去许多毒力基因的实验室毒株中也保留了下来，这表明US27和US28在病毒感染过程中各自进化出了独特而重要的功能。
