Sullivan B L, Knopoff E J, Saifuddin M, Takefman D M, Saarloos M N, Sha B E, Spear G T
Department of Immunology/Microbiology, Rush University, Chicago, IL 60612, USA.
J Immunol. 1996 Aug 15;157(4):1791-8.
This study was undertaken to directly assess the susceptibility of HIV-1 plasma virus to C-mediated lysis. Plasma from HIV-infected individuals was collected and ultracentrifuged over 20% sucrose to isolate virions from plasma components including anticoagulants, which inhibit C activity. Treatment with C alone in the absence of exogenously added Ab caused lysis of virus from all patients (n = 18) (range 14 to 86%). This lysis occurred via the classical C pathway and was not due to cross-reactive Abs in the C source. Protein A bound a fraction of isolated plasma virus and this binding was blocked by purified human Ig suggesting that anti-HIV Abs bound to plasma virus could be responsible for inducing C activation. A portion of virus bound to CR2 on cells in the absence of exogenously added C indicating that virus activated C in vivo. C levels from six of six patients were determined to be sufficient to lead to lysis of virus in vivo. Since plasma virus appeared more sensitive to C than primary isolates, isolated virus was evaluated for the presence of C control proteins. While primary isolate virions contained CD46, CD55, and CD59, only CD59 was detected on plasma virus. The results of this study strongly suggest that C is activated by a portion of plasma virus in vivo due to the binding of Ab. The resultant opsonization plus subsequent lysis may be important routes of clearance and destruction of plasma virus in infected persons.
本研究旨在直接评估HIV-1血浆病毒对补体（C）介导裂解的敏感性。收集HIV感染个体的血浆，并在20%蔗糖上进行超速离心，以从包括抗凝剂在内的血浆成分中分离病毒粒子，抗凝剂会抑制补体活性。在没有外源添加抗体的情况下，仅用补体处理导致所有患者（n = 18）的病毒裂解（范围为14%至86%）。这种裂解通过经典补体途径发生，并非由于补体来源中的交叉反应性抗体。蛋白A结合了一部分分离的血浆病毒，这种结合被纯化的人Ig阻断，表明与血浆病毒结合的抗HIV抗体可能是诱导补体激活的原因。在没有外源添加补体的情况下，一部分病毒与细胞上的CR2结合，表明病毒在体内激活补体。确定六名患者中有六名的补体水平足以在体内导致病毒裂解。由于血浆病毒似乎比原代分离株对补体更敏感，因此评估分离病毒中补体控制蛋白的存在情况。虽然原代分离病毒粒子含有CD46、CD55和CD59，但在血浆病毒上仅检测到CD59。这项研究的结果强烈表明，由于抗体的结合，补体在体内被一部分血浆病毒激活。由此产生的调理作用以及随后的裂解可能是感染个体中血浆病毒清除和破坏的重要途径。
