REGULATION OF SIMIAN FOAMY VIRUS GENE EXPRESSION

猿泡沫病毒基因表达的调控

• 批准号: 3742082
• 负责人: PAUL A LUCIW
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3742082
• 关键词: Cercopithecidae; Macaca mulatta; Retroviridae; gene expression; genetic enhancer element; genetic promoter element; genetic regulatory element; site directed mutagenesis; tissue /cell culture; transcription factor

Simian and human foamy viruses (HFV and SFV) have complex genome structures which encode the gag, pol, and env genes for virion proteins as well as additional open reading frames (PRFS). One of these is a viral transactivator, designated TAF for SFV and bel-1 for HFV, which augments transcription directed by 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. We have demonstrated that SFV-1 from a rhesus macaque and SFV-3 from an african green monkey also encode an internal promoter in the env gene by utilizing transient expression assays in several tissue culture cell lines and by analyzing viral transcripts in infected cells. 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; 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 (TREIP) 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 a unique enhancer-like element regulated by the viral transactivator.

猴和人泡沫病毒（HFV和SFV）基因组复杂 编码病毒体蛋白的gag、pol和env基因的结构 以及附加的开放阅读帧（PRFS）。 其中一个是 病毒反式激活因子，SFV称为TAF，HFV称为bel-1， 通过长末端重复序列（LTR）增强转录 LTR的U3结构域中的顺式作用靶标。 近日，一名内部 转录启动子已经在3'端内的序列中被鉴定。 HFV env基因的末端。 我们已经证明，来自恒河猴的SFV-1 猕猴和来自非洲绿色猴的SFV-3也编码一种内部的 在env基因启动子中通过利用瞬时表达测定， 几种组织培养细胞系，并通过分析病毒转录本， 被感染的细胞 转录由内部启动子指导， SFV-1和SFV-3被taf-1和taf-3基因产物激活， 分别在几种细胞类型中。 塔塔盒子的重要性 通过定点突变建立SFV-1内部启动子; 在内部启动子中起始的转录物的5'端已经被 测定 SFV-1 env基因中的顺式作用序列是SFV-1感染所必需的。 对taf-1的应答包含在位于taf-1的5'端的121 bp元件内。 在内部启动子中的tata框。 这种taf-1反应元件在 内部启动子（TREIP）在一个位置起作用， 在异源启动子中以不依赖于方向的方式存在，因此具有 依赖于TAF-1活性的增强子的性质。 比对显示，SFV-1内部启动子和SFV-1 LTR具有相同的启动子序列。 序列相关性很小。 交叉反式激活研究表明， SFV-1和HFV的反式激活因子在内部启动子上起作用， 同源病毒的LTR，但不对异源病毒。 在 总之，猿猴和人类泡沫病毒的基因组直接影响病毒的 通过LTR中的启动子和内部的 启动子，每个启动子包含一个独特的 由病毒反式激活因子调节的增强子样元件。