Jahid Sohail, Bundy Linda M, Granger Steven W, Fan Hung
Cancer Research Institute, Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Virology. 2006 Jul 20;351(1):7-17. doi: 10.1016/j.virol.2006.03.010. Epub 2006 Apr 17.
SRS 19-6 MuLV is a murine retrovirus originally isolated in mainland China. A noteworthy feature of this virus (referred to as SRS MuLV here) induces tumors of multiple hematopoietic lineages, including myeloid, erythroid, T-lymphoid and B-lymphoid. To identify the determinants of disease specificity, chimeras between SRS and Moloney MuLV (M-MuLV) were generated by molecular cloning, and the pathogenic properties of the chimeras were investigated. The results indicated that, while the M-MuLV LTR can confer lymphoid specificity to SRS MuLV, the SRS LTR by itself was not sufficient to confer multiple lineage tumorigenesis to M-MuLV; additional sequences in gag or pol were also required. Thus, a secondary determinant for myeloid/erythroid leukemia in SRS MuLV is located in gag-pol. In these chimeras, an independent determinant for T-lymphoma was found in M-MuLV gag-pol. It was also interesting that insertion of M-MuLV env into SRS MuLV decreased the rate of leukemogenicity, while insertion of SRS env into M-MuLV (SEM) accelerated leukemogenesis. The enhanced pathogenicity of SEM was found to correlate with earlier formation of MCF recombinants. The basis for the accelerated MCF recombinant formation was investigated. The endogenous polytropic MuLV env sequences contributing to several SEM MCF recombinants were identified, and the cross-over points were identified. While no obvious differences in the relative homologies between SRS MuLV env and polytropic env vs. M-MuLV and polytropic envs suggested a reason for the more rapid MCF recombinant formation, an overlapping but different set of polytropic env proviruses were found to participate in MCF formation for M-MuLV vs. SEM. Thus, the mechanisms for MCF formation appear to differ for M-MuLV and SEM.
SRS 19-6 MuLV是一种最初在中国内地分离出的鼠逆转录病毒。这种病毒（此处称为SRS MuLV）的一个显著特征是可诱导多种造血谱系发生肿瘤，包括髓系、红系、T淋巴细胞系和B淋巴细胞系。为了确定疾病特异性的决定因素，通过分子克隆构建了SRS和莫洛尼氏鼠白血病病毒（M-MuLV）之间的嵌合体，并研究了这些嵌合体的致病特性。结果表明，虽然M-MuLV长末端重复序列（LTR）可赋予SRS MuLV淋巴细胞特异性，但单独的SRS LTR不足以赋予M-MuLV多谱系肿瘤发生能力；gag或pol基因中的其他序列也是必需的。因此，SRS MuLV中髓系/红系白血病的二级决定因素位于gag-pol基因中。在这些嵌合体中，在M-MuLV gag-pol基因中发现了T淋巴瘤的独立决定因素。同样有趣的是，将M-MuLV env基因插入SRS MuLV会降低致白血病率，而将SRS env基因插入M-MuLV（SEM）则会加速白血病发生。发现SEM增强的致病性与MCF重组体的更早形成相关。研究了MCF重组体加速形成的基础。鉴定了促成几个SEM MCF重组体的内源性多嗜性MuLV env序列，并确定了交叉点。虽然SRS MuLV env与多嗜性env之间的相对同源性与M-MuLV和多嗜性env之间没有明显差异，这表明了MCF重组体形成更快的一个原因，但发现一组重叠但不同的多嗜性env前病毒参与了M-MuLV与SEM的MCF形成。因此，M-MuLV和SEM的MCF形成机制似乎不同。
