Quinnan G V, Zhang P F, Fu D W, Dong M, Margolick J B
Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
AIDS Res Hum Retroviruses. 1998 Jul 20;14(11):939-49. doi: 10.1089/aid.1998.14.939.
Changes in neutralizing antibody (NA) titers in stored sera collected over 5 years from 10 participants in the Multicenter AIDS Cohort Study (MACS) were evaluated. The participants were HIV-1 infected on enrollment in the MACS, and remained AIDS free during the 5-year study interval. Seven viruses derived from molecular clones were used in NA assays; five of the viruses were T tropic (NL4-3, ALA1, NY5, SF2, and Z2Z6) and two were M tropic [AD8 and NL(SF162)]. In addition, pseudoviruses (PVs) were constructed that expressed envelope genes from NL4-3, ALA1, AD8, and SF162 and from primary viruses from two MACS participants (PV-9 and PV-10). There was significant correlation between NA titers obtained in four of five virus/PV comparisons, while the SF162 PV was more sensitive to NA than the corresponding virus. Comparable changes in NA titers were detected using viruses and PVs. Fourfold or greater increases in NA titers were noted in each of the participants, involving recognition of one to five of the nine strains tested. In some patients these NA titer changes appeared as discrete episodes of immune responses, while in others there may have been either multiple episodes or continuous evolution of the NA responses. The data indicate that changes in NA specificity occur during HIV-1 infection, which may result from the occurrence of neutralization escape mutation. The use of PVs for the study of phenotypic characteristics of envelope glycoproteins should facilitate the study of neutralization escape mutation in HIV-1 infection.
对多中心艾滋病队列研究（MACS）中10名参与者在5年期间收集的储存血清中的中和抗体（NA）滴度变化进行了评估。这些参与者在加入MACS时感染了HIV-1，并且在5年的研究期间未患艾滋病。在NA检测中使用了7种源自分子克隆的病毒；其中5种病毒是T嗜性的（NL4-3、ALA1、NY5、SF2和Z2Z6），2种是M嗜性的[AD8和NL(SF162)]。此外，构建了表达来自NL4-3、ALA1、AD8和SF162以及两名MACS参与者的原代病毒（PV-9和PV-10）包膜基因的假病毒（PV）。在五种病毒/PV比较中的四种中获得的NA滴度之间存在显著相关性，而SF162 PV比相应病毒对NA更敏感。使用病毒和PV检测到NA滴度有可比的变化。在每个参与者中都观察到NA滴度有四倍或更大的增加，涉及对所测试的九种毒株中的一至五种的识别。在一些患者中，这些NA滴度变化表现为免疫反应的离散发作，而在其他患者中，NA反应可能有多次发作或持续演变。数据表明，在HIV-1感染期间NA特异性会发生变化，这可能是由于中和逃逸突变的发生。使用PV研究包膜糖蛋白的表型特征应有助于研究HIV-1感染中的中和逃逸突变。
