Molecular and phylogenetic analyses of a new amphotropic murine leukemia virus (MuLV-1313)
Molecular and phylogenetic analyses of a new amphotropic murine leukemia virus (MuLV-1313)
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DOI：
10.1186/1743-422x-3-101
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发表时间：
2006-12-05
期刊：
影响因子：
4.8
通讯作者：
Rasheed, Suraiya
中科院分区：
文献类型：
--
作者：
Howard, Thomas M.;Sheng, Zhijuan;Rasheed, Suraiya
背景资料：嗜中性鼠白血病病毒（MuLV-A）是天然存在的外源获得性γ逆转录病毒，是南加州野生小鼠的固有病毒。这些病毒在包括体外人类细胞在内的广泛细胞类型中复制，并且它们可以在野生和近交系实验室小鼠中引起血液学和神经系统疾病。由于MuLV-A还表现出离散干扰和中和特性，这些病毒的包膜蛋白对于研究病毒-宿主细胞相互作用以及作为将外源基因转移到包括人细胞在内的多种宿主中的载体是非常有用的。然而，几种已知的MuLV-A的基因组结构尚未建立，嗜热逆转录病毒与许多外源或内源MuLV株的进化关系仍然难以捉摸.在此，我们提出了一种新的嗜热病毒MuLV-1313的完整的遗传结构，并证明这种逆转录病毒与其他MuLV-A的属于一个独特的分子，生物学和系统发育类之间的MuLV株分离自大量的实验室近交系或野生小鼠。MuLV- 1313的宿主范围与先前分离的MuLV-A相似，除了该病毒在哺乳动物细胞以及鸡细胞中有效复制。与其它MuLV-A的ENV蛋白（4070 A、1504 A和10A-1）相比，MuLV- 1313的gp 70蛋白在其信号肽和富含脯氨酸的铰链区中表现出差异。然而，MuLV- 1313包膜蛋白与从全球各种近交系和野生小鼠中分离的广泛鼠逆转录病毒中存在的那些完全无关。通过点图分析对整个MuLV- 1313基因组进行遗传分析，将一个基因组的每个核苷酸与另一个基因组的相应核苷酸进行比较，结果表明，除env基因外，该病毒的基因组与生物学上不同的野生小鼠嗜亲性逆转录病毒更密切相关（Cas-Br-E）分离自南加州的另一个区域，而不是其全长序列存在于GenBank中的15个MuLV毒株中的任何一个。MuLV-1313的整个基因组序列的系统发育分析和层次聚类证实了这一发现，这也将所有MULV-A置于从全球许多小鼠品系分离的逆转录病毒大家族中的遗传学上不同的类别中。同样地，构建MuLV- 1313的Gag、PoI和Env蛋白中的每一种的单独树状图表明，与所有已知的MuLV毒株相比，嗜热性逆转录病毒属于在遗传学上排他的γ逆转录病毒组。分子，与一个大的外源性逆转录病毒家族相比，包括MuLV-1313在内的嗜亲性逆转录病毒的生物学和系统发育特性是不同的，或内源性传播的实验室和野生小鼠的嗜亲性、嗜多性和异嗜性MuLV株。此外，无论是自然发生的嗜亲性和生物学上离散的嗜亲性反转录病毒的南加州野生小鼠是更密切相关的进化树上彼此比任何其他哺乳动物γ反转录病毒，表明这些病毒的共同起源。这是第一次报告的一个完整的基因组分析的一组独特的遗传学上不同的嗜热病毒。
Background: The amphotropic murine leukemia viruses (MuLV-A's) are naturally occurring, exogenously acquired gammaretroviruses that are indigenous to the Southern California wild mice. These viruses replicate in a wide range of cell types including human cells in vitro and they can cause both hematological and neurological disorders in feral as well as in the inbred laboratory mice. Since MuLV-A's also exhibit discrete interference and neutralization properties, the envelope proteins of these viruses have been extremely useful for studying virus-host cell interactions and as vehicles for transfer of foreign genes into a variety of hosts including human cells. However, the genomic structure of any of the several known MuLV- A's has not been established and the evolutionary relationship of amphotropic retroviruses to the numerous exogenous or endogenous MuLV strains remains elusive. Herein we present a complete genetic structure of a novel amphotropic virus designated MuLV-1313 and demonstrate that this retrovirus together with other MuLV-A's belongs to a distinct molecular, biological and phylogenetic class among the MuLV strains isolated from a large number of the laboratory inbred or feral mice.Results: The host range of MuLV- 1313 is similar to the previously isolated MuLV- A's except that this virus replicates efficiently in mammalian as well as in chicken cells. Compared to ENV proteins of other MuLV-A's (4070A, 1504A and 10A-1), the gp70 protein of MuLV- 1313 exhibits differences in its signal peptides and the proline-rich hinge regions. However, the MuLV- 1313 envelope protein is totally unrelated to those present in a broad range of murine retroviruses that have been isolated from various inbred and feral mice globally. Genetic analysis of the entire MuLV- 1313 genome by dot plot analyses, which compares each nucleotide of one genome with the corresponding nucleotide of another, revealed that the genome of this virus, with the exception of the env gene, is more closely related to the biologically distinct wild mouse ecotropic retrovirus (Cas-Br-E) isolated from another region of the Southern California, than to any of the 15 MuLV strains whose full-length sequences are present in the GenBank. This finding was corroborated by phylogenetic analyses and hierarchical clustering of the entire genomic sequence of MuLV-1313, which also placed all MULV-A's in a genetically distinct category among the large family of retroviruses isolated from numerous mouse strains globally. Likewise, construction of separate dendrograms for each of the Gag, PoI and Env proteins of MuLV- 1313 demonstrated that the amphotropic retroviruses belong to a phylogenetically exclusive group of gammaretroviruses compared to all known MuLV strains.Conclusion: The molecular, biological and phylogenetic properties of amphotropic retroviruses including MuLV-1313 are distinct compared to a large family of exogenously- or endogenouslytransmitted ecotropic, polytropic and xenotropic MuLV strains of the laboratory and feral mice. Further, both the naturally occurring amphotropic and a biologically discrete ecotropic retrovirus of the Southern California wild mice are more closely related to each other on the evolutionary tree than any other mammalian gammaretrovirus indicating a common origin of these viruses. This is the first report of a complete genomic analysis of a unique group of phylogenetically distinct amphotropic virus.