Chen H, He J, Fong S, Wilcox G, Wood C
School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, USA.
J Virol. 2000 Mar;74(6):2703-13. doi: 10.1128/jvi.74.6.2703-2713.2000.
Jembrana disease virus (JDV) is a bovine lentivirus genetically similar to bovine immunodeficiency virus; it causes an acute and sometimes fatal disease in infected animals. This virus carries a very potent Tat that can strongly activate not only its own long terminal repeat (LTR) but also the human immunodeficiency virus (HIV) LTR. In contrast, HIV Tat cannot reciprocally activate the JDV LTR (H. Chen, G. E. Wilcox, G. Kertayadnya, and C. Wood, J. Virol. 73:658-666, 1999). This indicates that in transactivation JDV Tat may utilize a mechanism similar to but not the same as that of the HIV Tat. To further study the similarity of JDV and HIV tat in transactivation, we first tested the responses of a series of HIV LTR mutants to the JDV Tat. Cross-transactivation of HIV LTR by JDV Tat was impaired by mutations that disrupted the HIV type 1 transactivation response element (TAR) RNA stem-loop structure. Our results demonstrated that JDV Tat, like HIV Tat, transactivated the HIV LTR at least partially in a TAR-dependent manner. However, the sequence in the loop region of TAR was not as critical for the function of JDV Tat as it was for HIV Tat. The competitive inhibition of Tat-induced transactivation by the truncated JDV or HIV Tat, which consisted only of the activation domain, suggested that similar cellular factors were involved in both JDV and HIV Tat-induced transactivation. Based on the one-round transfection assay with HIV tat mutant proviruses, the cotransfected JDV tat plasmid can functionally complement the HIV tat defect. To further characterize the effect of JDV Tat on HIV, a stable chimeric HIV carrying the JDV tat gene was generated. This chimeric HIV replicated in a T-cell line, C8166, and in peripheral blood mononuclear cells, which suggested that JDV Tat can functionally substitute for HIV Tat. Further characterization of this chimeric virus will help to elucidate how JDV Tat functions and to explain the differences between HIV and JDV Tat transactivation.
杰姆布拉纳病病毒（JDV）是一种与牛免疫缺陷病毒在基因上相似的牛慢病毒；它在受感染动物中引发一种急性且有时致命的疾病。这种病毒携带一种非常强效的反式激活因子（Tat），它不仅能强烈激活自身的长末端重复序列（LTR），还能激活人类免疫缺陷病毒（HIV）的LTR。相比之下，HIV Tat不能反过来激活JDV的LTR（H. Chen、G. E. Wilcox、G. Kertayadnya和C. Wood，《病毒学杂志》73:658 - 666，1999年）。这表明在反式激活过程中，JDV Tat可能利用了一种与HIV Tat类似但不完全相同的机制。为了进一步研究JDV和HIV Tat在反式激活方面的相似性，我们首先测试了一系列HIV LTR突变体对JDV Tat的反应。破坏了1型HIV反式激活应答元件（TAR）RNA茎环结构的突变会损害JDV Tat对HIV LTR的交叉反式激活。我们的结果表明，与HIV Tat一样，JDV Tat至少部分以TAR依赖的方式反式激活HIV LTR。然而，TAR环区域的序列对JDV Tat功能的关键程度不如对HIV Tat功能的关键程度。仅由激活结构域组成的截短型JDV或HIV Tat对Tat诱导的反式激活的竞争性抑制表明，相似的细胞因子参与了JDV和HIV Tat诱导反式激活过程。基于用HIV tat突变体原病毒进行的一轮转染试验，共转染的JDV tat质粒在功能上可以弥补HIV tat的缺陷。为了进一步表征JDV Tat对HIV的影响，则构建了一个携带JDV tat基因的稳定嵌合HIV。这种嵌合HIV在T细胞系C8166和外周血单核细胞中复制，这表明JDV Tat在功能上可以替代HIV Tat。对这种嵌合病毒的进一步表征将有助于阐明JDV Tat的功能方式，并解释HIV和JDV Tat反式激活之间的差异。
