BIOLOGY OF HUMAN AIDS RETROVIRUS

人类免疫缺陷病毒（HIV）引起多种临床 表现如机会性感染、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 在过去的一年里，来自艾滋病毒前瞻性临床研究的大脑样本 痴呆症被用来鉴定HIV包膜C2中的重要序列 和V3区，在痴呆和非痴呆艾滋病患者中存在差异。 来自两组的序列也克隆在感染性质粒中， 在所有情况下都发现是嗜巨噬细胞的。 这些结果 这与大多数HIV病毒株存在于大脑中的解释一致， 是感染脑小胶质细胞的嗜巨噬细胞株，但 艾滋病痴呆似乎与一个独特的子集的出现相关 嗜巨噬细胞的病毒，导致痴呆症， 机制等 最近的研究集中在体外感染人类 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，并可能发挥不同的作用， 体内发病机制

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.