Klasse P J, McKeating J A, Schutten M, Reitz M S, Robert-Guroff M
Institute of Medical Microbiology, Lund University, Sweden.
Virology. 1993 Sep;196(1):332-7. doi: 10.1006/viro.1993.1484.
An immune-selected point-mutation (HXB2-Env:Ala582(-->Thr)) in the transmembrane protein, gp41, of the human immunodeficiency virus type 1 confers relative insensitivity to neutralization by a number of sera from HIV-1-positive persons. Affinity-purified human antibodies to continuous epitopes spanning Ala582 do not neutralize the virus (C. Wilson, M. S. Reitz, Jr., K. Aldrich, P. J. Klasse, J. Blomberg, R. C. Gallo, and M. J. Robert-Guroff, J. Virol. 64, 3240-3248, 1990). The specificity of the antibodies that the mutation renders less active has not previously been determined. We now report that this substitution in gp41 reduces the neutralizing activity of monoclonal antibodies to discontinuous gp120 epitopes, which overlap with the CD4-binding site. There was no such difference in sensitivity to neutralization by soluble CD4, CD4-immunoglobulin, or by two monoclonal antibodies to the V3 region of gp120. Furthermore, the ability of 10 human HIV-1-positive sera to block the binding of soluble CD4 to mammalian-recombinant gp120 correlated weakly with their differentiation of neutralization between the wild-type and the Env:Ala582(-->Thr)-mutant virus. We thus suggest that the substitution in gp41 modulates the conformation of gp120 so as to decrease viral sensitivity to one category of antibodies which is partly responsible for the group-specific neutralization of HIV-1 by human sera.
人类免疫缺陷病毒1型跨膜蛋白gp41中的一个免疫选择点突变（HXB2-Env:Ala582（-->Thr））使该病毒对许多HIV-1阳性者的血清中和作用具有相对抗性。亲和纯化的针对跨越Ala582的连续表位的人源抗体不能中和该病毒（C. 威尔逊、小M. S. 雷茨、K. 奥尔德里奇、P. J. 克拉瑟、J. 布洛姆伯格、R. C. 加洛和M. J. 罗伯特-古罗夫，《病毒学杂志》64卷，3240 - 3248页，1990年）。此前尚未确定该突变使其活性降低的抗体的特异性。我们现在报告，gp41中的这种替代降低了针对与CD4结合位点重叠的不连续gp120表位的单克隆抗体的中和活性。在对可溶性CD4、CD4免疫球蛋白或针对gp120 V3区的两种单克隆抗体的中和敏感性方面没有这种差异。此外，10份人类HIV-1阳性血清阻断可溶性CD4与哺乳动物重组gp120结合的能力与其区分野生型和Env:Ala582（-->Thr）突变型病毒中和作用的能力之间的相关性较弱。因此，我们认为gp41中的替代调节了gp120的构象，从而降低了病毒对一类抗体的敏感性，这类抗体部分负责人类血清对HIV-1的组特异性中和作用。
