Faraji-Shadan F, Stubbs J D, Bowman P D
Department of Biology, San Francisco State University, CA 94132.
Med Hypotheses. 1990 Jun;32(2):81-4. doi: 10.1016/0306-9877(90)90027-c.
It is proposed here that a form of intracellular immunity can be devised which would protect cells from virus infection and, in particular, could be used as a treatment for the human immunodeficiency virus (HIV) infected individual. Following in vitro immunization of naive human B lymphocytes with reverse-transcriptase (RT) or HIV transactivator protein (tat), messenger RNA (mRNA) would be isolated from these cells. Using the mRNA molecules as templates, copy DNA (cDNA) molecules encoding the RT or tat-specific immunoglobulins, are prepared and amplified by the polymerase chain reaction. After engineering of the antibody encoding cDNAs to provide appropriate intracellular addressing information, the cDNAs would be used to transfect stem cells of HIV infected individuals in vitro. The presence, in the cytoplasm and nucleus, of antibodies which had been selected to interfere with the reproduction of the virus, would protect these cells from infection. Autologous transplantation of such cells would confer resistance against HIV replication by these stem cells and their progeny in the treated individual. Such a strategy may also be useful against other retroviruses and could provide resistance against retrovirally triggered leukemia.
本文提出，可以设计一种细胞内免疫形式，它能保护细胞免受病毒感染，特别是可用于治疗人类免疫缺陷病毒（HIV）感染者。在用逆转录酶（RT）或HIV反式激活蛋白（tat）对未致敏的人B淋巴细胞进行体外免疫后，从这些细胞中分离信使核糖核酸（mRNA）。以mRNA分子为模板，制备编码RT或tat特异性免疫球蛋白的互补脱氧核糖核酸（cDNA）分子，并通过聚合酶链反应进行扩增。在对编码抗体的cDNA进行改造以提供适当的细胞内定位信息后，这些cDNA将用于在体外转染HIV感染者的干细胞。选择的能干扰病毒复制的抗体在细胞质和细胞核中的存在，将保护这些细胞免受感染。这种细胞的自体移植将使这些干细胞及其后代在接受治疗的个体中对HIV复制产生抗性。这样的策略可能对其他逆转录病毒也有用，并且可以提供对逆转录病毒引发的白血病的抗性。
