Enhancement of Human Immunodeficiency Virus Type 1 lnCection by Antisera to Peptides from the Envelope Glycoproteins gp120/gp41
Enhancement of Human Immunodeficiency Virus Type 1 lnCection by Antisera to Peptides from the Envelope Glycoproteins gp120/gp41
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发表时间：
2003
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通讯作者：
Shibo Jiang;Kang Lin;A. Neurath
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作者：
Shibo Jiang;Kang Lin;A. Neurath
人类免疫缺陷病毒1型(HIV-1)包膜糖蛋白(gp120和gp41)可诱导病毒中和抗体(VNAB)和增强HIV-1感染的抗体(EAB)。已经定义了几个引起VNAB的表位，主要的病毒中和决定簇被分配给gp120的V3环。为了为抗HIV疫苗的合理设计提供背景，定义引起EAB的结构域似乎也很重要。这是通过筛选几乎覆盖整个gp120/gp41序列的合成肽的抗血清来实现的，以增强MT-2细胞(一种连续的T细胞系)感染HIV-1的效果。在人类补体存在的情况下，许多抗血清(16/30)显著增强了HIV-1。补体受体2型(CK2)的抗体消除了抗体介导的HIV-1感染的增强。21个不同的HIV-1分离株的V3高变环的抗血清也被测试了它们对HIV-11.B感染的增强作用。其中11份为VNAb，10份为HIV-LMB增强型感染。所有具有病毒增强活性的抗血清都含有与HIV-LMB的V3环发生交叉反应的抗体，且随着血清学交叉反应的增加，病毒增强活性增强。这些结果表明，如果免疫原上的抗原表位与感染人群的主要HIV-1毒株表位不够匹配，即在血清学上发生交叉反应，但不是在病毒中和水平上，那么包含V3环的抗原免疫可能会引起EAB，而不是保护性抗体。
Human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (gp120 and gp41) elicit virus-neutralizing antibodies (VNAB) and also antibodies enhancing HIV-1 infection (EAB). Several epitopes eliciting VNAB have been defined, the principal virus-neutralizing determinant being assigned to the V3 loop of gp120. To provide a background for a rational design of antiHIV vaccines, it also appears important to define domains eliciting EAB. This was accomplished by screening antisera against synthetic peptides covering almost the entire sequence of gp120/gp41 for their enhancing effects on HIV-1 infection of MT-2 cells, a continuous T cell line. Many (16/30) of the antisera significantly enhanced HIV-1 in the presence of human complement. Antibodies to complement receptor type 2 (CK2) abrogated the antibody-mediated enhancement of HIV-1 infection. Antisera to V3 hypervariable loops of 21 distinct HIV-1 isolates were also tested for their enhancing effects on HIV-11.B infection. 11 of these sera contained VNAB and 10 enhanced HIV-lmB infection. All antisera with virus-enhancing activity contained antibodies crossreactive with the V3 loop of HIV-lmB, and the virus-enhancing activity increased with increasing serological crossreactivity. These results suggest that immunization with antigens encompassing V3 loops may elicit EAB rather than protective antibodies if epitopes on the immunogen and the predominant HIV-1 isolate infecting a population are insufficiently matched, i.e., crossreactive serologically but not at the level of virus neutralization.