BIOLOGY OF HUMAN AIDS RETROVIRUS

人类艾滋病逆转录病毒的生物学

• 批准号: 2566777
• 负责人: B CHESEBRO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/2566777
• 关键词: HIV envelope protein; human immunodeficiency virus 1; human tissue; macrophage; microorganism culture; nucleic acid sequence; protein sequence; vascular endothelium; virus genetics; virus infection mechanism; virus replication

Human immunodeficiency virus (HIV) causes a variety of clinical manifestations such as opportunistic infection, Kaposi's sarcoma, wasting syndrome, and neurological defects. The main goal of this project is to determine the role of variation in viral sequences in causing these different syndromes. Studies this year have mainly focussed on the role of the V3 region of envelope in influencing HIV-1 infection of macrophages. Two nonmacrophage-tropic patient derived clones were compared to a prototype macrophage-tropic clone. The results indicated that specific amino acids at five V3 positions influenced macrophage tropism, whereas amino acids at three to four different positions influenced syncytia induction(SI or NSI phenotype) in lymphocytes. These experiments revealed that macrophage tropism and the NSI phenotype were different phenotypes controlled independently by different viral sequences rather than two phenotypic representations of the same viral gene function. Additional studies have also involved in vitro infection of human macrophages by HIV strains which vary in replication levels in macrophages. This variation was found to occur only in macrophages and not in lymphocytes, and it correlated with sequence differences in the envelope V1 and V2 regions. Immunostaining of virus-positive cells at various times after infection showed that high replication levels were due to viral spread in the macrophages whereas low replication levels were seen in viruses which were unable to spread to new cells after initial infection. These two replication phenotypes have been seen in primary AIDS patient HIV isolates and might play different roles in pathogenesis in vivo. Further experiments have been carried out studying the role of HIV-1 variation on influencing tropism for human brain capillary endothelial cells. Results so far suggest that a region at the N-terminus of the env gene is important for this cell tropism.

人类免疫缺陷病毒（HIV）引起多种临床 表现为机会性感染、卡波西肉瘤、消瘦 综合征和神经缺陷。 该项目的主要目标是 确定病毒序列变异在导致这些 不同的综合征 今年的研究主要集中在V3区的作用， 包膜影响HIV-1感染巨噬细胞。 两 将非嗜巨噬细胞患者衍生的克隆与原型进行比较， 嗜巨噬细胞克隆。 结果表明，特定氨基酸 在五个V3位置影响巨噬细胞嗜性，而氨基酸 在三到四个不同的位置影响合胞体诱导（SI或 NSI表型）。 这些实验表明， 嗜巨噬细胞性和NSI表型是不同的表型 由不同的病毒序列独立控制，而不是两个 相同病毒基因功能的表型表现。 另外的研究还涉及体外感染人类 巨噬细胞的艾滋病毒株，不同的复制水平， 巨噬细胞 发现这种变化仅发生在巨噬细胞中， 而不是在淋巴细胞中，它与序列差异相关， 包络V1和V2区域。 病毒阳性细胞的免疫染色， 感染后的不同时间表明，高复制水平是 由于病毒在巨噬细胞中传播， 这些病毒在感染后不能扩散到新细胞中， 初始感染。 这两种复制表型已经在 原发性艾滋病患者的HIV分离株，并可能在 体内发病机制。 已经进行了进一步的实验，研究HIV-1的作用， 影响人脑毛细血管内皮细胞趋向性的变异 细胞 到目前为止的结果表明，在env的N-末端的区域， 基因对于这种细胞向性是重要的。