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T淋巴细胞亚群 单抗OKT4或Leu-3a。这种专一性是通过 至少部分是由于病毒与所表达的T4抗原的关联 在这些细胞的表面。病毒上与之结合的结构 这种抗原，以及调节T4表达的细胞因子 病毒感染后的分子和影响细胞病变效应 仍有待确定。这项提案将调查 HTLV-III与T4细胞在三个区域。1)努力找出 与T4结合所需的病毒相关决定因素 淋巴细胞。初步观察表明，该病毒可能 在萌发过程中选择性地整合HLC II类(DR)决定因素 细胞表面。细胞来源的DR抗原可能是 病毒粒子在感染T4细胞期间的利用将进一步 调查过了。此外，抗T4的单抗可以抑制 病毒结合将被用于生产抗独特型作为一种策略 鉴定与T4结合的病毒粒子上的结构。2)因素 它调节T4抗原和细胞受体的表达 将对HTLV-III进行评估。这项建议将进一步探索 佛波酯调节T4的表达的研究结果 并降低T4细胞对HTLV-III感染的易感性。 病毒渗透/感染和病毒感染之间可能的相互作用 除了发现之外，还将对激活蛋白激酶C进行研究 佛波酯改变T4细胞系的能力 感染HTLV-III以支持病毒生产。3)最新发现 已经表明，除了细胞死亡外，艾滋病逆转录病毒还可能 产生一种无细胞毒性的、持续感染正常外周血的T4 淋巴细胞。这表明，一系列生物学后果可能 发生在HTLV-III感染之后。HTLV-III的细胞病变效应 感染将在T4细胞系中进行评估，这些细胞系对 抗原、同种异体抗原或有丝分裂原。将努力确定主机 影响感染后细胞毒性的因素和功能 当发生非细胞毒性感染时对T4细胞的影响。

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.