ENHANCEMENT OF SIV INFECTION WITH SOLUBLE RECEPTOR MOLECULES

ENHANCEMENT OF SIV INFECTION WITH SOLUBLE RECEPTOR MOLECULES
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DOI:
10.1126/science.2309120
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发表时间:
1990-03-02
期刊:
影响因子:
56.9
通讯作者:
BUCK, DW
BUCK, DW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
ALLAN, JS;STRAUSS, J;BUCK, DW

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人类T细胞上的CD4受体已被证明在人类免疫缺陷病毒1型(HIV-1)感染过程中发挥着不可或缺的作用。为了确定SIVagm感染的关键T细胞表面受体,检测了重组人可溶性CD4(RCD4)对SIVagm(一种自然感染非洲绿猴的类似HIV病毒)的抑制能力。研究发现,rCD4可使人类T细胞系的SIVagm感染增加18倍,而rCDr可阻断HIV-1感染。在SIVagm感染后的24小时内观察到合胞体的形成和从头蛋白的合成,而在没有rCD4的情况下这个过程需要4到6天。这种增强作用可被针对rCD4的单抗所抑制。来自自然感染的非洲绿猴的抗体抑制效价从1:2,000到1:10,000可以消除这种增强作用;这些抗体在没有rCD4的情况下不能中和SIVagm感染。RCD4对SIVagm感染的病毒增强作用可能是通过GP12-CD4结合调节病毒膜,从而促进病毒融合和穿透的继发性事件。
The CD4 receptor on human T cells has been shown to play an integral part in the human immunodeficiency virus type 1 (HIV-1) infection process. Recombinant soluble human CD4 (rCD4) was tested for its ability to inhibit SIV agm, an HIV-like virus that naturally infects African green monkey, in order to define T cell surface receptors critical for SIVagm infection. teh rCD4 was found to enhance SIVagm infection of a human T cell line by as much as 18-fold, whereas HIV-1 infection was blocked by rCDr. Induction of syncytium formation and de novo protein synthesis were observed within the first 24 hours after SIVagm infection, whereas this process took 4 to 6 days in the absence of rCD4. This enhancing effect could be inhibited by monoclonal antibodies directed to rCD4. The enhancing effect could be abrogated with antibodies from naturally infected African green monkeys inhibitory titers of from 1:2,000 to 1:10,000; these antibodies did not neutralize SIVagm infection in the absence of rCD4. Viral enhancement of SIVagm infection by rCD4 may result from the modulation of the viral membrane through gp12-CD4 binding, thus facilitating secondary events involved in viral fusion and penetration.