CHARACTERIZATION AND CLINICAL-ASSOCIATION OF ANTIBODY INHIBITORY TO HIV REVERSE-TRANSCRIPTASE ACTIVITY

CHARACTERIZATION AND CLINICAL-ASSOCIATION OF ANTIBODY INHIBITORY TO HIV REVERSE-TRANSCRIPTASE ACTIVITY
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DOI:
10.1126/science.2435004
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发表时间:
1987-03-20
期刊:
影响因子:
56.9
通讯作者:
KULKOSKY, J
KULKOSKY, J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LAURENCE, J;SAUNDERS, A;KULKOSKY, J

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人免疫缺陷病毒(HIV)的逆转录酶活性在体外被来自感染这种逆转录病毒的某些个体的免疫球蛋白G(IgG)阻断。观察到酶功能抑制的异源性免疫应答。催化活性被抑制50%或更多的使用10微克的IgG从11 16艾滋病毒血清阳性的无症状携带者,但从0 8血清阴性对照和2 12例获得性免疫缺陷综合征(艾滋病)或艾滋病相关复合体(ARC)。抑制剂被限制在F(ab“)2片段。它不是针对poly(rA). cntdot的。寡聚(dT)模板,也不针对主要包膜或结构病毒抗原,并且不与细菌、禽类或其他哺乳动物DNA聚合酶交叉反应。它没有相关的聚合酶抗原的放射免疫沉淀识别。这种抑制剂的丧失可能与临床疾病的发展有关。10个无症状的HIV血清阳性携带者与高滴度的IgG抗体逆转录酶进行了跟踪平均3年。所有四个失去了抑制能力之前,艾滋病或ARC的发展,而滴度持续在六个谁保持临床健康。
Reverse transcriptase activity of the human immunodeficiency virus (HIV) was blocked in vitro by immunoglobulin G (IgG) derived from certain individuals infected with this retrovirus. A heterogenous immune response for inhibition of enzyme function was noted. Catalytic activity was depressed by 50% or more with the use of 10 micrograms of IgG from 11 of 16 HIV-seropositive asymptomatic carriers, but from 0 of 8 seronegative controls and 2 of 12 patients with acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The inhibitor was confined to the F(ab'')2 fragment. It was not directed against the poly(rA) .cntdot. oligo(dT) template, nor against major envelope or structural viral antigens, and did not cross-react with bacterial, avian, or other mammalian DNA polymerases. It did not correlate with recognition of polymerase antigens by radioimmunoprecipitation. Loss of this inhibitor may be associated with development of clinical disease. Ten asymptomatic HIV-seropositive carriers with high titers of IgG antibodies to reverse transcriptase were followed for a mean of 3 years. All of four lost inhibitory capability prior to development of AIDS or ARC, while titers persist in the six who remain clinically healthy.