PATHOGENESIS OF HUMAN IMMUNODEFICIENCY VIRUS 1 (HIV 1)

与HIV-1感染相关的临床综合征--艾滋病占主导地位 由CD4+T细胞耗尽和IS引起的免疫缺陷 表现为反复感染机会主义生物体。 然而，越来越多的与艾滋病毒相关的综合症，如 卡波西肉瘤、艾滋病痴呆综合征和HIV相关性肾病 似乎是病毒或病毒蛋白更直接作用的结果 在宿主组织上。这些研究的目的是探索 细胞和分子机制负责产生这些 与艾滋病毒相关的疾病。为了实现这一目标，我们有 利用了许多细胞和分子生物学方法。我们 已经创造了在缺乏HIV基因的情况下表达HIV基因的转基因小鼠系 病毒复制发展为艾滋病样恶病质综合征，银屑病 皮肤损伤和肾脏疾病。从这些动物身上找到的证据 证实了病毒蛋白在艾滋病发病机制中的重要作用。 因此，我们正在调查针对感染者的靶向机制 T细胞结合到特定的宿主组织。我们已经证明T细胞感染了 HIV-1与纤维连接蛋白结合，这种结合是由 细胞表面a5b1整合素表达增加。一旦连接上 在基底膜上，感染HIV-1的T细胞产生胶原酶并 侵入人工基底膜。实验室中的最新研究 是为了更好地了解特定的病毒蛋白 对这些症状的诱发以及对 治疗干预的策略。

The clinical syndrome associated with HIV-1 infection, AIDS, is dominated by immune deficiency resulting from CD4+ T-cell depletion and is manifested by recurrent infections with opportunistic organisms. Increasingly, however, several of the HIV-associated syndromes such as Kaposi's sarcoma, AIDS dementia complex, and HIV-associated nephropathy appear to be the result of a more direct effect of virus or viral proteins on host tissues. The objective of these studies is to explore the cellular and molecular mechanisms responsible for the generation of these HIV-associated diseases. In order to accomplish this objective, we have utilized a number of cellular and molecular biological approaches. We have created transgenic mouse lines expressing HIV genes in the absence of viral replication which develop an AIDS-like cachexia syndrome, psoriatic skin lesions, and renal disease. Evidence from these animals substantiates the important role of viral proteins in AIDS pathogenesis. As a result, we are investigating mechanism for the targeting of infected T-cells to specific host tissues. We have shown that T-cells infected with HIV-1 attach to fibronectin and that attachment is mediated by increased expression of a5b1 integrin on the cell surface. Once attached to the basement membrane, HIV-1 infected T-cells produce collagenase and invade artificial basement membranes. Current studies in the laboratory are directed to a better understanding of the specific viral proteins responsible for inducing these syndromes as well as the development of strategies for therapeutic intervention.