BIOLOGY OF HUMAN AIDS RETROVIRUS

人类艾滋病逆转录病毒的生物学

• 批准号: 5200474
• 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/5200474
• 关键词: AIDS dementia complex; CD4 molecule; HeLa cells; genetic polymorphism; human immunodeficiency virus; human tissue; macrophage; microglia; microorganism culture; molecular cloning; nucleic acid sequence; plasmids; protein sequence; virulence; virus envelope; 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. 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.

人类免疫缺陷病毒（HIV）引起多种临床症状 机会性感染、卡波西肉瘤、消瘦等表现 综合征和神经系统缺陷。 该项目的主要目标是 确定病毒序列变异在引起这些情况中的作用 不同的综合症。 去年，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。 两组的序列也被克隆到感染性质粒中并 在所有情况下都发现是巨噬细胞嗜性的。 这些结果是 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菌株，但是 HIV痴呆似乎与一个独特亚群的出现相关 嗜巨噬细胞病毒通过尚不清楚的方式引起痴呆 机制。 最近的研究主要集中在人类体外感染 HIV病毒株的巨噬细胞在复制水平上有所不同 巨噬细胞。 发现这种变异仅发生在巨噬细胞中 不在淋巴细胞中，并且与淋巴细胞中的序列差异相关 包络线 V1 和 V2 区域。 病毒阳性细胞的免疫染色 感染后多次显示高复制水平 由于病毒在巨噬细胞中传播，而复制水平低 在无法传播到新细胞的病毒中发现 初次感染。 这两种复制表型已在 原发性艾滋病患者的艾滋病病毒分离株可能在其中发挥不同的作用 体内发病机制。