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恒河猴巨细胞病毒的全序列及基因组分析

Complete sequence and genomic analysis of rhesus cytomegalovirus.

作者信息

Hansen Scott G, Strelow Lisa I, Franchi David C, Anders David G, Wong Scott W

机构信息

Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon 97006, USA.

出版信息

J Virol. 2003 Jun;77(12):6620-36. doi: 10.1128/jvi.77.12.6620-6636.2003.

Abstract

The complete DNA sequence of rhesus cytomegalovirus (RhCMV) strain 68-1 was determined with the whole-genome shotgun approach on virion DNA. The RhCMV genome is 221,459 bp in length and possesses a 49% G+C base composition. The genome contains 230 potential open reading frames (ORFs) of 100 or more codons that are arranged colinearly with counterparts of previously sequenced betaherpesviruses such as human cytomegalovirus (HCMV). Of the 230 RhCMV ORFs, 138 (60%) are homologous to known HCMV proteins. The conserved ORFs include the structural, replicative, and transcriptional regulatory proteins, immune evasion elements, G protein-coupled receptors, and immunoglobulin homologues. Interestingly, the RhCMV genome also contains sequences with homology to cyclooxygenase-2, an enzyme associated with inflammatory processes. Closer examination identified a series of candidate exons with the capacity to encode a full-length cyclooxygenase-2 protein. Counterparts of cyclooxygenase-2 have not been found in other sequenced herpesviruses. The availability of the complete RhCMV sequence along with the ability to grow RhCMV in vitro will facilitate the construction of recombinant viral strains for identifying viral determinants of CMV pathogenicity in the experimentally infected rhesus macaque and to the development of CMV as a vaccine vector.

摘要

采用全基因组鸟枪法对恒河猴巨细胞病毒(RhCMV)68 - 1株的病毒体DNA进行测序,确定了其完整的DNA序列。RhCMV基因组长度为221,459 bp,G + C碱基组成为49%。该基因组包含230个潜在的开放阅读框(ORF),每个ORF至少有100个密码子,它们与先前测序的β疱疹病毒(如人巨细胞病毒(HCMV))的对应序列呈共线性排列。在这230个RhCMV ORF中,有138个(60%)与已知的HCMV蛋白同源。保守的ORF包括结构蛋白、复制蛋白、转录调节蛋白、免疫逃逸元件、G蛋白偶联受体和免疫球蛋白同源物。有趣的是,RhCMV基因组还包含与环氧化酶 - 2具有同源性的序列,环氧化酶 - 2是一种与炎症过程相关的酶。进一步检查发现了一系列能够编码全长环氧化酶 - 2蛋白的候选外显子。在其他已测序的疱疹病毒中尚未发现环氧化酶 - 2的对应物。完整的RhCMV序列的获得以及在体外培养RhCMV的能力,将有助于构建重组病毒株,用于在实验感染的恒河猴中鉴定CMV致病性的病毒决定因素,并推动将CMV开发为疫苗载体。

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