CHARACTERIZATION OF PRIMATE RETROVIRUSES

灵长类逆转录病毒的特征

• 批准号: 6289103
• 负责人: RAOUL BENVENISTE
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/6289103
• 关键词: HIV infections; Macaca; Retroviridae; disease /disorder model; human tissue; nucleic acid sequence; protein sequence; simian AIDSs; simian immunodeficiency virus; virulence; virus antigen; virus genetics; virus infection mechanism; virus protein

Molecular changes in Nef with progression to AIDS. We have compared nef gene sequences isolated by polymerase chain reaction from peripheral blood lymphocyte DNA of macaques which had been inoculated with either biologically (E11S) or molecularly cloned SIV/Mne (clone 8). Two samples from each animal obtained early (wk 2-8) or late (wk 21-137) after infection were analyzed. Four substitutions in the predicted Nef amino acid sequence were seen in all animals at the late time point, and a fifth in all but one. Two of the common exchanges are located about 40 residues apart in the Nef core sequence, but are in proximity on the tertiary structure as judged by computer modeling using the structure of the HIV Nef core protein as a guide. Most recurring in vivo changes replaced a residue found in the cloned Nef sequence with one present in a consensus derived by aligning the Nef sequences of the SIV/Sm clade. Animals inoculated with virus already containing the late version nef gene developed a more aggressive disease. Recombinant virus containing a macaque adapted nef (MA-nef) on the clone 8 backbone was threefold more infectious on SMAGI cells than the original virus. A lymphocyte line infected with SIV-clone8MA-nef contained a large proportion of cells carrying proviruses with defective nef genes. These findings suggest that the nef gene of the cloned SIV/Mne had undergone attenuating mutations during propagation in tissue culture which were corrected in vivo. Chimeric viruses containing the late nef gene sequence associated with AIDS will be tested for pathogenicity in macaques in vivo. Nef and progression to AIDS - AIDS, antiviral, baboons, foamy retrovirus, macaques, simian immunodeficiency virus, - Human Tissues, Fluids, Cells, etc.

NEF的分子变化，进展为AIDS。我们已经比较了通过猕猴的外周血淋巴细胞DNA分离的NEF基因序列，这些NEF链反应已被生物学上（E11S）或分子克隆的SIV/MNE接种（克隆8）。分析感染后早期获得的每只动物（WK 2-8）或晚期（WK 21-137）的两个样品。在晚期的所有动物中，在预测的NEF氨基酸序列中进行了四个取代，除一个动物外，所有动物均观察到五分之一。在NEF核心序列中，有两个常见的交换位于大约40个残基，但使用HIV NEF NEF NEF核心蛋白的结构作为指导来判断的第三纪结构上的距离。大多数反复出现的体内变化代替了克隆的NEF序列中发现的残基，其中一个存在通过对齐SIV/SM进化片的NEF序列来得出的共识中。接种已接种已包含晚期NEF基因的病毒的动物患有更具侵略性的疾病。在克隆8主链上含有猕猴适应性NEF（MA-NEF）的重组病毒比原始病毒更感染性Smagi细胞。感染SIV-CLONE8MA-NEF的淋巴细胞系包含大部分带有有缺陷NEF基因的原病毒的细胞。这些发现表明，克隆的SIV/MNE的NEF基因在组织培养过程中的传播过程中经历了衰减突变，这些突变在体内校正。含有与艾滋病相关的晚期NEF基因序列的嵌合病毒将在体内猕猴中的致病性测试。 NEF和向AIDS的进展 - 艾滋病，抗病毒，狒狒，泡沫逆转录病毒，猕猴，猿猴免疫缺陷病毒， - 人体组织，液体，细胞等。