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。 在过去的一年中，一项关于艾滋病毒的前瞻性临床研究的大脑样本 痴呆被用来识别HIV包膜C2中的重要序列 痴呆型和非痴呆型艾滋病患者的V3区不同。 来自两组的序列也被克隆到感染质粒中，并 在所有病例中均发现嗜巨噬细胞。这些结果是 与大多数HIV毒株存在于大脑中的解释一致 是感染大脑小胶质细胞的嗜巨噬细胞菌株，但 HIV痴呆症似乎与一种独特的亚群的出现有关 嗜巨噬细胞病毒通过尚不清楚的方式引起痴呆 机械装置。 最近的研究集中在人类的体外感染上。 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 活体发病机制。

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. In the past year brain samples from a prospective clinical study on HIV dementia were used to identify significant sequences in HIV envelope C2 and V3 regions which differed in demented and nondemented AIDS patients. Sequences from both groups were also cloned in infectious plasmids and were found to be macrophage-tropic in all cases. These results are consistent with the interpretation that most HIV strains present in brain are macrophage-tropic strains which infect brain microglial cells, but HIV dementia appears to correlate with the appearance of a unique subset of macrophage-tropic viruses which cause dementia via as yet unknown mechanisms. More recent studies have focussed on 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 in vivo pathogenesis.