BIOLOGY OF HUMAN AIDS RETROVIRUS

人类免疫缺陷病毒（HIV）感染与几种 不同的临床综合征，包括免疫抑制，卡波西氏 肉瘤、消耗综合征和神经系统异常，如 痴呆 本项目的目标是了解 病毒基因的变异导致了这些不同的综合征。 我们最近发现，能够感染巨噬细胞的艾滋病毒株 在它们的包膜的氨基酸序列上有很强的同源性 高变区V3蛋白。 其他工作已经证实 这种嗜巨噬细胞的HIV病毒株似乎是 在不同的个体之间通过性传播。 多种多样 在疾病后期看到的V3序列似乎演变成 在每一个感染者身上。 因此，嗜巨噬细胞 包膜共有序列可能是一个理想的靶点， 疫苗应该有针对性。 在最近的研究中，我们分析了V3包络序列， 一组艾滋病患者伴和不伴艾滋病痴呆。 而大脑 来自两组的艾滋病毒似乎与 嗜巨噬细胞的HIV毒株，来自痴呆症患者的病毒显示， 与非痴呆患者的差异显著。 这些 结果表明，艾滋病痴呆症可能是由一个独特的子集， 嗜巨噬细胞的HIV病毒株。 原发性艾滋病患者HIV分离株及实验室适应能力 使用HeLa-CD 4克隆研究了HIV分离株体外感染细胞 表达不同数量的CD 4。 适应性强的艾滋病毒显示出 在广泛的CD 4表达范围内具有相似的感染性水平。 在 相比之下，主要患者HIV分离株的感染性直接 与HeLa细胞上表达的CD 4的量成比例。 这些结果 证明在包膜基因的重要功能差异， 主要患者HIV分离株可能参与各种体内 致病作用

Human immunodeficiency virus (HIV) infection is associated with several different clinical syndromes including immunosuppression, Kaposi's sarcoma, wasting syndrome, and neurological abnormalities such as dementia. The goal of this project is to understand the role of variation in the viral genes in causing these diverse syndromes. We recently showed that HIV strains with ability to infect macrophages shared a strong homology in the amino acid sequences of their envelope proteins in the hypervariable V3 region. Other work has now confirmed that such macrophage-tropic HIV strains appear to be the main ones sexually transmitted between different individuals. The wide diversity of V3 sequences seen at later disease stages appears to evolve independently in each infected individual. Thus, the macrophage-tropic envelope consensus sequence may be an ideal target to which potential vaccines should be directed. In more recent studies we have analyzed V3 envelope sequences from a group of AIDS patients with and without HIV dementia. Whereas brain derived HIV from both groups appeared to be closely related to macrophage-tropic HIV strains, viruses from demented patients showed significant differences from those from non-demented patients. These results suggested that HIV dementia might be caused by a unique subset of macrophage-tropic HIV strains. The ability of primary AIDS patient HIV isolates and laboratory-adapted HIV isolates to infect cells in vitro was studied using HeLa-CD4 clones expressing differing amounts of CD4. Laboratory-adapted HIV showed a similar level of infectivity over a wide range of CD4 expression. In contrast, infectivity of primary patient HIV isolates was directly proportional to the amount of CD4 expressed on HeLa cells. These results demonstrate important functional differences in the envelope genes of primary patient HIV isolates which could be involved in various in vivo pathogenic effects.