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恒河猴巨细胞病毒的基因组测序和特征分析。

Genomic sequencing and characterization of cynomolgus macaque cytomegalovirus.

机构信息

Department of Microbiology, Mount Sinai Hospital, Room 1484, 600 University Avenue, Toronto, ON, Canada.

出版信息

J Virol. 2011 Dec;85(24):12995-3009. doi: 10.1128/JVI.05840-11. Epub 2011 Oct 12.

Abstract

Cytomegalovirus (CMV) infection is the most common opportunistic infection in immunosuppressed individuals, such as transplant recipients or people living with HIV/AIDS, and congenital CMV is the leading viral cause of developmental disabilities in infants. Due to the highly species-specific nature of CMV, animal models that closely recapitulate human CMV (HCMV) are of growing importance for vaccine development. Here we present the genomic sequence of a novel nonhuman primate CMV from cynomolgus macaques (Macaca fascicularis; CyCMV). CyCMV (Ottawa strain) was isolated from the urine of a healthy, captive-bred, 4-year-old cynomolgus macaque of Philippine origin, and the viral genome was sequenced using next-generation Illumina sequencing to an average of 516-fold coverage. The CyCMV genome is 218,041 bp in length, with 49.5% G+C content and 84% protein-coding density. We have identified 262 putative open reading frames (ORFs) with an average coding length of 789 bp. The genomic organization of CyCMV is largely colinear with that of rhesus macaque CMV (RhCMV). Of the 262 CyCMV ORFs, 137 are homologous to HCMV genes, 243 are homologous to RhCMV 68.1, and 200 are homologous to RhCMV 180.92. CyCMV encodes four ORFs that are not present in RhCMV strain 68.1 or 180.92 but have homologies with HCMV (UL30, UL74A, UL126, and UL146). Similar to HCMV, CyCMV does not produce the RhCMV-specific viral homologue of cyclooxygenase-2. This newly characterized CMV may provide a novel model in which to study CMV biology and HCMV vaccine development.

摘要

巨细胞病毒(CMV)感染是免疫抑制个体(如移植受者或艾滋病毒/艾滋病患者)中最常见的机会性感染,先天性 CMV 是导致婴儿发育障碍的主要病毒原因。由于 CMV 具有高度种特异性,因此越来越需要能够重现人类 CMV(HCMV)的动物模型来进行疫苗开发。在这里,我们介绍了一种来自食蟹猴(Macaca fascicularis;CyCMV)的新型非人类灵长类动物 CMV 的基因组序列。CyCMV(渥太华株)是从一只 4 岁、菲律宾原产、圈养的健康食蟹猴的尿液中分离出来的,使用下一代 Illumina 测序技术对病毒基因组进行测序,平均覆盖率为 516 倍。CyCMV 基因组长 218,041 bp,G+C 含量为 49.5%,蛋白质编码密度为 84%。我们鉴定出 262 个推定的开放阅读框(ORF),平均编码长度为 789 bp。CyCMV 的基因组组织与恒河猴 CMV(RhCMV)大致相似。在 262 个 CyCMV ORF 中,有 137 个与 HCMV 基因同源,243 个与 RhCMV 68.1 同源,200 个与 RhCMV 180.92 同源。CyCMV 编码 4 个 ORF,这些 ORF 不存在于 RhCMV 株 68.1 或 180.92 中,但与 HCMV 具有同源性(UL30、UL74A、UL126 和 UL146)。与 HCMV 相似,CyCMV 不产生 RhCMV 特异性环氧化酶-2 病毒同源物。这种新描述的 CMV 可能为研究 CMV 生物学和 HCMV 疫苗开发提供一种新的模型。

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