ID SEQUENCE ELEMENT ABOVE POLYPURINE TRACT ESSENTIAL FOR SIV REPLICATION

多嘌呤束上方的 ID 序列元素对于 SIV 复制至关重要

• 批准号: 6116563
• 负责人: PETR O ILYINSKII
• 金额: $ 10.61万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116563
• 关键词: AIDS; animal tissue; communicable diseases; immunology; inflammation; lymphatic system; virus

A short stretch of T-rich sequences immediately upstream of the polypurine tract (PPT) is highly conserved in the proviral genomes of human and simian immunodeficiency viruses (HIV and SIV) To investigate whether this "U-box" influences SIVmac239 replication, we analyzed the properties of mutants with changes in this region of the viral genome All mutants were either retarded in their growth (up to one month delay) or did not replicate detectably in CEMx174 cells When U-box mutants did replicate detectably, compensatory changes were consistently observed in the viral genome The most common compensatory change was the acquisition of thymidines immediately upstream of the PPT, but marked expansion in the length of the PPT was also observed U-box mutants produced transiently by transfection were severely impaired in their ability to produce reverse transcripts in infectivity assays Analysis of transiently produced mutant virus revealed no defect in RNA pack agin g or virus assembly These results identify a new structural element important for an early step in the viral life cycle that includes reverse transcription PUBLICATIONS Ilyinskii, PO and Desrosiers, RC Identification of a sequence element immediately upstream of the polypurine tract that is essential for replication of simian immunodeficiency virus EMBO J 1998; 17:3766-3774

一小段富含T细胞的序列， 多嘌呤段（PPT）在前病毒基因组中高度保守 人类和猿猴免疫缺陷病毒（HIV和SIV） 无论这个“U盒”是否影响SIVmac 239复制，我们分析了 病毒基因组该区域发生变化的突变体的特性 所有突变体的生长要么迟缓（最多一个月 延迟）或在CEMx 174细胞中未检测到复制。 突变体复制检测，补偿性变化， 在病毒基因组中始终观察到的最常见的代偿性 变化是胸腺嘧啶的收购紧接上游 PPT，但也观察到PPT长度的显著扩张 通过转染瞬时产生的U盒突变体被严重破坏。 他们的能力受损，产生逆转录， 瞬时产生的突变病毒的分析 显示RNA包装阿金g或病毒装配无缺陷。 确定一个新的结构要素， 包括逆转录在内的病毒生命周期 Ilyinskii，PO和Desrosiers，RC序列元件的鉴定 紧接着多嘌呤道的上游， 猿免疫缺陷病毒的复制EMBO J 1998; 17：3766-3774