MOUSE MAMMARY-TUMOR VIRUSES WITH FUNCTIONAL SUPERANTIGEN GENES ARE SELECTED DURING IN-VIVO INFECTION
MOUSE MAMMARY-TUMOR VIRUSES WITH FUNCTIONAL SUPERANTIGEN GENES ARE SELECTED DURING IN-VIVO INFECTION
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DOI：
10.1073/pnas.92.11.4828
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发表时间：
1995-05-23
影响因子：
11.1
通讯作者：
ROSS, SR
中科院分区：
文献类型：
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作者：
GOLOVKINA, TV;DUDLEY, JP;ROSS, SR
小鼠乳腺肿瘤病毒（MMTV）编码一种对体内病毒感染性很重要的超抗原。为了确定乳源性 MMTV 感染是否需要超抗原功能，我们创建了 HYB PRO/Cla 转基因小鼠。这些小鼠产生了全长、包装的病毒RNA，其带有移码突变，导致超抗原蛋白过早终止。年轻的 HYB PRO/Cla 小鼠没有表现出同源 V(beta)14(+) T 细胞的缺失，尽管它们在乳汁中排出病毒。 HYB PRO/Cla 小鼠的非转基因后代感染了这种病毒，因为在它们的乳腺中检测到了转基因特异性病毒转录本。令人惊讶的是，这些后代表现出外源MMTV（C3H）感染特征的V（β）14（+）T细胞的逐渐缺失。序列分析表明，这些新获得的病毒已经重建了由 HYB PRO/Cla 和内源 Mtv-1 前病毒 RNA 之间重组产生的超抗原开放阅读框。因此，在感染过程中对具有功能性超抗原基因的MMTV进行选择。
Mouse mammary tumor virus (MMTV) encodes a superantigen that is important for viral infectivity in vivo. To determine whether superantigen function was required for infection by milk-borne MMTV, we created HYB PRO/Cla transgenic mice. These mice produced a full-length, packaged viral RNA with a frameshift mutation that caused premature termination of the superantigen protein. Young HYB PRO/Cla mice showed no deletion of their cognate V(beta)14(+) T cells, although they shed virus in their milk The nontransgenic offspring of the HYB PRO/Cla mice were infected with this virus, since transgene specific viral transcripts were detected in their mammary glands. Surprisingly, these offspring demonstrated the progressive deletion of V(beta)14(+) T cells characteristic of exogenous MMTV(C3H) infection. Sequence analysis demonstrated that these newly acquired viruses had reconstituted superantigen open reading frames resulting from recombination between the HYB PRO/Cla and endogenous Mtv-1 proviral RNAs. Thus, there is selection during the infection process for MMTVs with functional superantigen genes.