Corbett Alexandra J, Forbes Catherine A, Moro Dorian, Scalzo Anthony A
Centre for Experimental Immunology, Lions Eye Institute, 2 Verdun Street, Nedlands, WA 6009, Australia.
Immunology and Virology Program, Centre for Ophthalmology and Visual Science, University of Western Australia, Nedlands, WA 6009, Australia.
J Gen Virol. 2007 Mar;88(Pt 3):758-769. doi: 10.1099/vir.0.82623-0.
Murine cytomegalovirus (MCMV) is a widely used model for human cytomegalovirus (HCMV) and has facilitated many important discoveries about the biology of CMVs. Most of these studies are conducted using the laboratory MCMV strains Smith and K181. However, wild-derived isolates of MCMV, like HCMV clinical isolates, exhibit genetic variation from laboratory strains, particularly at the ends of their genomes in areas containing known or putative immune-evasion and tropism genes. This study analysed the nucleotide sequence of the m02-m05 region, within the m02 gene family, of a number of laboratory and wild-derived MCMV isolates, and found a large degree of variation in both the sequence and arrangement of genes. A new open reading frame (ORF), designated m03.5, was found to be present in a number of wild isolates of MCMV in place of m03. Two distinct isolates, W8 and W8211, were found to possess both m03 and m03.5. Both m03 and m03.5 had early transcription kinetics and the encoded proteins could be detected on the cell surface, consistent with a possible role in immune evasion through binding to host-cell proteins. These data show that gene duplication and sequence variation occur within different isolates of MCMV found in the wild. As this variation among strains may alter the function of genes, these findings should be considered when analysing gene function or host-virus interactions in laboratory models.
鼠巨细胞病毒（MCMV）是一种广泛用于研究人类巨细胞病毒（HCMV）的模型，它推动了许多关于巨细胞病毒生物学的重要发现。这些研究大多使用实验室MCMV菌株史密斯株和K181株进行。然而，与HCMV临床分离株一样，野生来源的MCMV分离株与实验室菌株存在遗传差异，特别是在其基因组末端含有已知或推测的免疫逃避和嗜性基因的区域。本研究分析了多个实验室和野生来源的MCMV分离株m02基因家族中m02 - m05区域的核苷酸序列，发现基因序列和排列存在很大差异。发现一个新的开放阅读框（ORF），命名为m03.5，在许多野生MCMV分离株中取代了m03。发现两个不同的分离株W8和W8211同时拥有m03和m03.5。m03和m03.5都具有早期转录动力学，并且编码的蛋白质可以在细胞表面检测到，这与通过与宿主细胞蛋白结合在免疫逃避中可能发挥的作用一致。这些数据表明，野生型MCMV不同分离株中发生了基因复制和序列变异。由于菌株间的这种变异可能会改变基因功能，因此在分析实验室模型中的基因功能或宿主 - 病毒相互作用时应考虑这些发现。
