INTERACTIONS OF HTLV-III WITH T4 CELLS

艾滋病逆转录病毒（HTLV-III、LAV和ARV）已显示出对 选择性感染由免疫细胞化学鉴定的T淋巴细胞亚群， 单克隆抗体OKT 4或Leu-3a。 这种特异性是在 至少部分是由于病毒与表达的T4抗原的结合 在这些细胞的表面。 病毒上的结构， 这种抗原和调节T4表达的细胞因子， 分子并影响病毒感染后的细胞病变效应 还有待确定。 本提案将研究以下因素之间的相互作用： HTLV-III与T4细胞在三个区域。 1)将努力查明 与T4结合所需的病毒相关决定簇 淋巴细胞 初步观察表明，该病毒可能 选择性地纳入HLC II类（DR）决定因素在萌芽过程中， 细胞表面。 细胞来源的DR抗原可能是 在T4细胞的感染期间由病毒体利用的细胞将进一步被 研究了 此外，单克隆抗T4抗体，其抑制 病毒结合将用于产生抗独特型，作为一种策略， 鉴定病毒体上与T4结合的结构。 2)因素 其调节T4抗原和细胞受体的表达， 将对HTLV-III进行评价。 该提案将进一步探讨 发现佛波醇酯调节T4的表达， 分子并降低T4细胞对HTLV-III感染的易感性。 病毒渗透/感染与 活化蛋白激酶-C将进行调查，除了发现 佛波醇酯改变了T4细胞系的能力， 感染HTLV-III以支持病毒生产。 3)最近的调查结果 已经表明，除了细胞死亡，艾滋病逆转录病毒也可能 产生正常外周血T4的非细胞毒性持续感染 淋巴细胞这表明，一系列生物学后果可能 发生在HTLV-III感染后。 HTLV-III的细胞病变效应 将在特异性响应于以下的T4细胞系中评价感染： 抗原、同种异体抗原或有丝分裂原。 将努力确定东道主 感染后影响细胞毒性的因素， 当非细胞毒性感染发生时，T4细胞的后果。

The AIDs-retroviruses (HTLV-III, LAV, and ARV) have shown a tropism for selectively infecting the T-lymphocyte subpopulation identified by the monoclonal antibodies OKT4 or Leu-3a. This specificity is mediated at least in part by the association of the virus with the T4 antigen expressed on the surface of these cells. The structures on the virus which bind to this antigen, and cellular factors which regulate the expression of the T4 molecule and influence cytopathic effects which follow viral infection remain to be determined. This proposal will investigate the interaction of HTLV-III with T4 cells in three areas. 1) Efforts will be made to identify the viral-associated determinants which are required for binding to T4 lymphocytes. Preliminary observations have suggested that the virus may selectively incorporate HLC class II (DR) determinants during budding from the cell surface. The possibility that DR antigens of cellular origin are utilized by the virion during infection of the T4 cell will be further investigated. In addition, monoclonal anti-T4 antibodies which inhibit viral binding will be used to produce anti-idiotypes as a strategy for identifying the structures on the virion which bind to T4. 2) Factors which regulate the expression of the T4 antigen and cellular receptors for HTLV-III will be evaluated. This proposal will further explore the findings that phorbol esters modulate both the expression of the T4 molecule and reduce the susceptability of T4 cells to HTLV-III infection. Possible interactions between viral penetration/infection and the activation protein kinase-C will be investigated, in addition to findings that phorbol esters alter the ability of T4 cell lines which are stably infected with HTLV-III to support viral production. 3) Recent findings have indicated that in addition to cell death, AIDS retroviruses may also produce a non-cytotoxic, persistent infection of normal peripheral blood T4 lymphocytes. This has suggested that a range of biological consequences may occur following HTLV-III infection. Cytopathic effects of HTLV-III infection will be evaluated in T4 cell lines specifically responsive to antigen, alloantigen or mitogen. Efforts will be made to determine host factors which influence cytotoxicity following infection, and functional consequences for the T4 cell when non-cytotoxic infection occurs.