BIOLOGY OF HUMAN AIDS RETROVIRUS

人类免疫缺陷病毒(HIV)引起多种临床症状 表现为机会性感染、卡波西氏肉瘤、消瘦 综合症和神经缺陷。这个项目的主要目标是 确定病毒序列变异在导致这些变化中的作用 不同的症状。 今年的研究主要集中在V3区的作用。 包膜在影响巨噬细胞感染HIV-1中的作用二 将非嗜巨噬细胞患者来源的克隆与原型进行比较 嗜巨噬细胞克隆。结果表明，特定的氨基酸 在5个V3位置影响巨噬细胞的趋向性，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， 巨噬细胞嗜性和NSI表型不同 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。 其他研究也涉及人类的体外感染。 巨噬细胞被复制水平不同的HIV毒株感染 巨噬细胞。这种变异只发生在巨噬细胞和 而不是在淋巴细胞中，而且它与 包络V1和V2区域。病毒阳性细胞的免疫染色 感染后的不同时间显示，高复制水平 由于病毒在巨噬细胞中传播，而复制水平较低 是在病毒中发现的，这些病毒在 最初的感染。这两种复制表型在 原发艾滋病患者HIV分离株，并可能在 体内致病机制。 已经进行了进一步的实验来研究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，在环境的N-末端的一个区域 基因对这种细胞嗜性很重要。

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.