Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element.
Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element.
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DOI：
10.1186/1742-4690-6-10
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发表时间：
2009-02-03
期刊：
影响因子：
3.3
通讯作者：
Dudley JP
中科院分区：
文献类型：
--
作者：
Mertz JA;Lozano MM;Dudley JP
小鼠乳腺肿瘤病毒（MMTV）编码Rem蛋白，这是一种HIV rev样蛋白，可增强啮齿动物细胞中未剪接病毒RNA的核输出。我们已经证明Rem是由双剪接RNA表达的，典型的复杂逆转录病毒。最近的一些报道表明MMTV可以感染人类细胞，表明MMTV可能与人类逆转录病毒相互作用，如人类免疫缺陷病毒（HIV）、人类t细胞白血病病毒（HTLV）和人类内源性K型逆转录病毒（HERV-K）。在本报告中，我们测试了人类复杂逆转录病毒的输出/调节蛋白是否会增加含有remre反应元件（RmRE）的载体的表达。MMTV Rem、HIV Rev和HTLV Rex蛋白增强了基于MMTV的报告质粒在人T细胞中的表达，而HERV-K Rec蛋白则不增强，并且这种活性依赖于RmRE。在HC11小鼠乳腺细胞中，Rev、Rex或Rec未检测到rmre依赖的报告基因表达。细胞分离和RNA定量实验表明，在MMTV报告系统中，调节蛋白不影响RNA稳定性或核输出。Rem对HIV、HTLV或HERV-K的输出因子没有明显的活性。与啮齿类动物细胞中Rem-特异性活性类似，人类细胞中Rem、Rev或Rex依赖于rmre的功能被一种作用于RNA和蛋白质输出的Crm1途径的显性阴性截断核孔蛋白抑制。这些数据表明，许多逆转录病毒调节蛋白识别相似的复杂RNA结构，这可能取决于细胞类型特异性蛋白的存在。逆转录病毒蛋白在RmRE上的活性似乎影响报告RNA的输出后功能。我们的研究结果提供了额外的证据，证明MMTV是一种复杂的逆转录病毒，在人类细胞中具有病毒相互作用的潜力。
Mouse mammary tumor virus (MMTV) encodes the Rem protein, an HIV Rev-like protein that enhances nuclear export of unspliced viral RNA in rodent cells. We have shown that Rem is expressed from a doubly spliced RNA, typical of complex retroviruses. Several recent reports indicate that MMTV can infect human cells, suggesting that MMTV might interact with human retroviruses, such as human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV), and human endogenous retrovirus type K (HERV-K). In this report, we test whether the export/regulatory proteins of human complex retroviruses will increase expression from vectors containing the Rem-responsive element (RmRE). MMTV Rem, HIV Rev, and HTLV Rex proteins, but not HERV-K Rec, enhanced expression from an MMTV-based reporter plasmid in human T cells, and this activity was dependent on the RmRE. No RmRE-dependent reporter gene expression was detectable using Rev, Rex, or Rec in HC11 mouse mammary cells. Cell fractionation and RNA quantitation experiments suggested that the regulatory proteins did not affect RNA stability or nuclear export in the MMTV reporter system. Rem had no demonstrable activity on export elements from HIV, HTLV, or HERV-K. Similar to the Rem-specific activity in rodent cells, the RmRE-dependent functions of Rem, Rev, or Rex in human cells were inhibited by a dominant-negative truncated nucleoporin that acts in the Crm1 pathway of RNA and protein export. These data argue that many retroviral regulatory proteins recognize similar complex RNA structures, which may depend on the presence of cell-type specific proteins. Retroviral protein activity on the RmRE appears to affect a post-export function of the reporter RNA. Our results provide additional evidence that MMTV is a complex retrovirus with the potential for viral interactions in human cells.
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影响因子：
64.5
作者：
Fornerod, M;Ohno, M;Mattaj, IW
通讯作者：
Mattaj, IW
影响因子：
3.8
作者：
Bindra, A.;Muradrasoli, S.;Blomberg, J.
通讯作者：
Blomberg, J.
影响因子：
5.4
作者：
Bhadra, S;Lozano, MM;Dudley, JP
通讯作者：
Dudley, JP
影响因子：
5.4
作者：
DUDLEY, JP;VARMUS, HE
通讯作者：
VARMUS, HE
DOI：
10.1073/pnas.92.11.4828
发表时间：
1995-05-23
影响因子：
11.1
作者：
GOLOVKINA, TV;DUDLEY, JP;ROSS, SR
通讯作者：
ROSS, SR