Campbell M, Renshaw-Gegg L, Renne R, Luciw P A
Department of Pathology, School of Medicine, University of California, Davis 95616.
J Virol. 1994 Aug;68(8):4811-20. doi: 10.1128/JVI.68.8.4811-4820.1994.
Simian and human foamy viruses (HFV and SFV), genetically related members of the spumavirus genus of retroviruses, have complex genome structures which encode the gag, pol, and env genes for virion proteins as well as additional open reading frames. One of these open reading frames is a viral transactivator, encoded by genes designated taf for SFV and bel-1 for HFV, which augments transcription directed by the long terminal repeat (LTR) through cis-acting targets in the U3 domain of the LTR. Recently, an internal transcriptional promoter has been identified in sequences within the 3' end of the HFV env gene (M. Lochelt, W. Muranyi, and R. M. Flugel, Proc. Natl. Acad. Sci. 90:7317-7321, 1993). We have demonstrated by using transient expression assays in several tissue culture cell lines and by analyzing viral transcripts in infected cells that SFV-1 from a rhesus macaque and SFV-3 from an African green monkey also encode an internal promoter in the env gene. Transcription directed by the internal promoters of SFV-1 and SFV-3 is activated by the taf-1 and taf-3 gene products, respectively, in several cell types. The importance of a TATA box for the SFV-1 internal promoter was established by site-specific mutagenesis, and the 5' ends of transcripts initiating in the internal promoter have been determined. cis-acting sequences in the SFV-1 env gene required for the response to taf-1 are contained within a 121-bp element located 5' to the TATA box in the internal promoter. This taf-1-responsive element in the internal promoter functions in a position- and orientation-independent fashion in a heterologous promoter and thus has the properties of an enhancer which depends on taf-1 activity. Alignments reveal that the SFV-1 internal promoter and the SFV-1 LTR have little sequence relatedness. Cross-transactivation studies show that the transactivators of SFV-1 and HFV function on the internal promoter and LTR of the homologous virus but not on the heterologous virus. In summary, the genomes of simian and human foamy viruses direct viral transcription through both the promoter in the LTR and an internal promoter within the env gene, and each promoter contains unique enhancer-like elements regulated by the viral transactivator.
猿猴泡沫病毒和人泡沫病毒（HFV和SFV）是逆转录病毒泡沫病毒属中基因相关的成员，具有复杂的基因组结构，可编码病毒粒子蛋白的gag、pol和env基因以及其他开放阅读框。其中一个开放阅读框是病毒反式激活因子，由SFV的taf基因和HFV的bel-1基因编码，它通过LTR的U3结构域中的顺式作用靶点增强由长末端重复序列（LTR）指导的转录。最近，在HFV env基因3'端的序列中鉴定出一个内部转录启动子（M. Lochelt、W. Muranyi和R. M. Flugel，《美国国家科学院院刊》90:7317 - 7321，1993）。我们通过在几种组织培养细胞系中进行瞬时表达分析以及分析感染细胞中的病毒转录本证明，恒河猴的SFV - 1和非洲绿猴的SFV - 3在env基因中也编码一个内部启动子。在几种细胞类型中，分别由taf - 1和taf - 3基因产物激活SFV - 1和SFV - 3内部启动子指导的转录。通过位点特异性诱变确定了TATA框对SFV - 1内部启动子的重要性，并确定了在内部启动子中起始的转录本的5'端。SFV - 1 env基因中对taf - 1反应所需的顺式作用序列包含在内部启动子中TATA框上游5'的一个121bp元件内。内部启动子中的这个taf - 1反应元件在异源启动子中以位置和方向独立的方式起作用，因此具有依赖于taf - 1活性的增强子的特性。序列比对显示SFV - 1内部启动子和SFV - 1 LTR几乎没有序列相关性。交叉反式激活研究表明，SFV - 1和HFV的反式激活因子在同源病毒的内部启动子和LTR上起作用，但不在异源病毒上起作用。总之，猿猴泡沫病毒和人泡沫病毒的基因组通过LTR中的启动子和env基因内的内部启动子指导病毒转录，并且每个启动子都包含由病毒反式激活因子调控的独特的增强子样元件。
