CONTROL OF PAPILLOMAVIRUS LATE TRANSCRIPTION

乳头瘤病毒是一种小的DNA肿瘤病毒，它能引起良性和 高等脊椎动物鳞状上皮的恶性病变。这个 这些病毒的完整裂解周期只发生在分化的 鳞状上皮的角质形成细胞。牛乳头瘤病毒1型 (BPV-1)作为模型系统，用于研究生物大分子的调控。 角质形成细胞分化过程中乳头瘤病毒基因的表达。就地 使用mRNA特异性探针的杂交研究表明， 这种调节既是转录的，也是转录后的。 利用最小晚期转录单位表达的转染法研究 载体已经证明，RNA处理发生在 湿疣的颗粒层是从早到晚转变的关键。 病毒式表达。抑制BPV-1的顺式作用调节元件 晚期基因表达已在3‘未翻译的晚期被鉴定 区域(Utr)。对该元素的突变分析表明， 一致的5‘剪接位点序列是其功能所必需的。在……里面 此外，该元件与U1 smRNA之间的碱基配对， 在剪接过程中，通常需要具有5‘剪接点的碱基对 元素的活动。但是，该元素不会出现 用于剪接，最有可能的功能是抑制 多聚(A)末位的多聚腺苷酸化。一种类似的抑制因素 在HPV-16晚期3‘非编码区中也被发现。HIV-1修订版 蛋白质，它与细胞剪接机制相互作用，以促进 未剪接的HIV mRNAs的核质粒运输，能够 逆转BPV-1 3‘非编码区元件对基因表达的影响 该载体还包含REV结合位点(RRE)。这表明 3‘非编码区元件的活性可由病毒或 细胞REV样蛋白。

The papillomaviruses are small DNA tumor viruses which cause benign and malignant lesions of squamous epithelia in higher vertebrates. The complete lytic cycle of these viruses occurs only in the differentiated keratinocytes of a squamous epithelium. Bovine papillomavirusus type 1 (BPV-1) was used as a model system for the study of the regulation of papillomavirus gene expression by keratinocyte differentiation. In situ hybridization studies using mRNA specific probes have demonstrated that this regulation is both transcriptional and posttranscriptional. Transfection studies using mini-late transcription unit expression vectors have demonstrated that RNA processing changes which occur in the granular layer of the wart are essential for the early to late shift in viral expression. A cis-acting regulatory element which inhibits BPV-1 late gene expression has been identified in the late 3' untranslated region (UTR). Mutational analysis of this element indicated that a consensus 5' splice site sequence is essential for its function. In addition, base pairing between this element and the U1 smRNA, which normally base pairs with 5' splice sites during splicing, is necessary for the activity of the element. This element, however, does not appear to be used for splicing and most likely functions by inhibiting polyadenylation at the late poly(A) site. A similar inhibitory element has also been identified in the HPV-16 late 3' UTR. The HIV-1 Rev protein, which interacts with cellular splicing machinery to facilitate the nucleocytoplasmid transport of unspliced HIV mRNAs, was able to reverse the effects of the BPV-1 3' UTR element on expression from a vector which also contained a Rev binding site (RRE). This suggests that the activity of the 3' UTR element could be regulated by a viral or cellular Rev-like protein.