Montefiori D C, Zhou I Y, Barnes B, Lake D, Hersh E M, Masuho Y, Lefkowitz L B
Department of Pathology, Vanderbilt University Medical School, Nashville, Tennessee 37232.
Virology. 1991 Jun;182(2):635-43. doi: 10.1016/0042-6822(91)90604-a.
Human immunodeficiency virus type 1 (HIV-1) exhibits extensive genomic and antigenic diversity, which is thought to contribute to the failure of the host's immune response to control infection and prevent clinical progression. Part of this failure may be due to utilization by the virus of antigenic variation as a means to escape protective immune responses. Antibody-escape variants of HIV-1 were studied here using fresh clinical isolates and autologous plasmas. HIV-1 was isolated from the plasma of seven people who were all seropositive for at least 2 years, and symptomatic sometime during that period. Isolated viruses were confirmed as HIV-1 by the presence of reverse transcriptase activity in infected culture supernatants, and by positive immunofluorescence using human monoclonal antibody to HIV-1 core protein. Plasma from these people were positive by Western immunoblot (DuPont) for most major HIV-1 (strain IIIB) antigens. These plasmas neutralized three laboratory strains of HIV-1 (i.e., IIIB, RF, and MN) but did not neutralize the homotypic strain in five cases, and had greatly reduced neutralizing titers against the homotypic strain in two cases. Homotypic neutralizing antibodies were absent in autologous plasma obtained 3 months later. When antibody titers were measured by fixed-cell indirect immunofluorescence assays (IFAs), high titers of IgG (1:6400 to 1:25,600) were detected against HIV-1 IIIB, while low titers of only 1:20 to 1:160 were detected against homotypic viral antigens at the time of virus isolation, and remained low 12 and 16 weeks later. No class IgA, IgD, IgE, or IgM antibodies to homotypic viral antigens, as possible IgG-blocking antibodies, were detected by fixed-cell IFAs. Cross-reactions with heterologous donor's plasmas were observed in some cases, and in these cases the cross-reactions were unidirectional. Live-cell IFAs detected IgG in patient's plasma to HIV-1 IIIB-infected cells but not to cells infected with homotypic isolates. These results suggest that it is common for neutralization-resistant HIV-1 variants to appear during the course of infection, and that all or most antigens of these variants are capable of escaping antibody recognition.
1型人类免疫缺陷病毒（HIV-1）具有广泛的基因组和抗原多样性，这被认为是导致宿主免疫反应无法控制感染并阻止临床进展的原因之一。这种失败的部分原因可能是病毒利用抗原变异作为逃避保护性免疫反应的一种手段。本文使用新鲜的临床分离株和自体血浆对HIV-1的抗体逃逸变异体进行了研究。从7名血清学阳性至少2年且在此期间某个时候出现症状的人的血浆中分离出HIV-1。通过感染培养上清液中存在逆转录酶活性以及使用针对HIV-1核心蛋白的人单克隆抗体进行阳性免疫荧光，确认分离出的病毒为HIV-1。这些人的血浆通过蛋白质免疫印迹法（杜邦）对大多数主要的HIV-1（IIIB株）抗原呈阳性。这些血浆中和了三种HIV-1实验室毒株（即IIIB、RF和MN），但在5例中未中和同源毒株，在2例中对同源毒株的中和效价大幅降低。3个月后获得的自体血浆中不存在同源中和抗体。当通过固定细胞间接免疫荧光测定法（IFA）测量抗体效价时，检测到针对HIV-1 IIIB的高滴度IgG（1:6400至1:25,600），而在病毒分离时针对同源病毒抗原仅检测到低滴度的1:20至1:160，并且在12周和16周后仍保持低水平。通过固定细胞IFA未检测到针对同源病毒抗原的IgA、IgD、IgE或IgM类抗体作为可能的IgG阻断抗体。在某些情况下观察到与异源供体血浆的交叉反应，并且在这些情况下交叉反应是单向的。活细胞IFA在患者血浆中检测到针对HIV-1 IIIB感染细胞的IgG，但未检测到针对同源分离株感染细胞的IgG。这些结果表明，在感染过程中出现中和抗性HIV-1变异体是常见的，并且这些变异体的所有或大多数抗原能够逃避抗体识别。
