An immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 (HXB2-Env:Ala 582(-->Thr)) decreases viral neutralization by monoclonal antibodies to the CD4-binding site.
An immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 (HXB2-Env:Ala 582(-->Thr)) decreases viral neutralization by monoclonal antibodies to the CD4-binding site.
复制标题
人类免疫缺陷病毒 1 型跨膜蛋白 (HXB2-Env:Ala 582(-->Thr)) 中的免疫选择点突变可降低单克隆抗体对 CD4 结合位点的病毒中和作用。
DOI：
10.1006/viro.1993.1484
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发表时间：
1993
期刊：
影响因子：
3.7
通讯作者：
M. Robert
中科院分区：
文献类型：
--
作者：
P. Klasse;J. McKeating;M. Schutten;Marvin S. Reitz;M. Robert
人类免疫缺陷病毒1型的跨膜蛋白gp 41中的免疫选择性点突变（HXB 2-Env：Ala 582（-->Thr））赋予对来自HIV-1阳性者的许多血清的中和相对不敏感性。针对跨越Ala 582的连续表位的亲和纯化的人抗体不中和病毒（C.威尔逊，M。S.小雷茨，K.作者：Aldrich，P. J. Klasse，J.布隆贝格，R. C. Gallo和M. J. Robert-Guroff，J. Virol. 64，3240-3248，1990）。突变使活性降低的抗体的特异性先前尚未确定。我们现在报告说，这种取代gp 41减少单克隆抗体的中和活性不连续gp 120表位，这与CD 4结合位点重叠。对可溶性CD 4、CD 4-免疫球蛋白或两种针对gp 120 V3区的单克隆抗体的中和敏感性没有这种差异。此外，10个人HIV-1阳性血清阻断可溶性CD 4与重组gp 120结合的能力与野生型和Env：Ala 582（-->Thr）突变病毒之间的中和差异弱相关。因此，我们认为，在gp 41的取代调制gp 120的构象，以降低病毒的敏感性，一类抗体是部分负责组特异性中和HIV-1的人血清。
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.