Study of the V3 Loop as a Target Epitope for Antibodies Involved in the Neutralization of Primary Isolates versus T-Cell-Line-Adapted Strains of Human Immunodeficiency Virus Type 1
Study of the V3 Loop as a Target Epitope for Antibodies Involved in the Neutralization of Primary Isolates versus T-Cell-Line-Adapted Strains of Human Immunodeficiency Virus Type 1
复制标题
V3 环作为抗体靶表位的研究，该抗体参与 1 型人类免疫缺陷病毒初级分离株与 T 细胞系适应株的中和
作者：
C. Spenlehauer;S. Saragosti;H. Fleury;A. Kirn;A. Aubertin;C. Moog
ABSTRACT Previous studies characterized the third variable (V3) loop of the envelope gp120 as the principal neutralizing determinant for laboratory T-cell-line-adapted (TCLA) strains of human immunodeficiency virus type 1 (HIV-1). However, primary viruses isolated from infected individuals are more refractory to neutralization than TCLA strains, suggesting that qualitatively different neutralizing antibodies may be involved. In this study, we investigated whether the V3 loop constitutes a linear target epitope for antibodies neutralizing primary isolates. By using peptides representative of the V3 regions of various primary isolates, an early, relatively specific and persistent antibody response was detected in sera from HIV-infected patients. To assess the relationship between these antibodies and neutralization, the same peptides were used in competition and depletion experiments. Addition of homologous V3 peptides led to a competitive inhibition in the neutralization of the TCLA strain HIVMN/MT-4 but had no effect on the neutralization of the autologous primary isolate. Similarly, the removal of antibodies that bind to linear V3 epitopes resulted in a loss of HIVMN/MT-4 neutralization, whereas no decrease in the autologous neutralization was measured. The different roles of V3-specific antibodies according to the virus considered were thereby brought to light. This confirmed the involvement of V3 antibodies in the neutralization of a TCLA strain but emphasized a more pronounced contribution of either conformational epitopes or epitopes outside the V3 loop as targets for antibodies neutralizing primary HIV-1 isolates. This result underlines the need to focus on new vaccinal immunogens with epitopes able to induce broadly reactive and efficient antibodies that neutralize a wide range of primary HIV-1 isolates.
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影响因子：
56.9
作者：
BURTON, DR;PYATI, J;BARBAS, CF
通讯作者：
BARBAS, CF
人类免疫缺陷病毒 gp41 和副粘病毒融合蛋白之间的序列相似性。
影响因子：
1.5
作者：
Gonzalez-Scarano,F;Waxham,MN;Ross,AM;Hoxie,JA
通讯作者：
Hoxie,JA
CD8 细胞抗 HIV 活性：非裂解性抑制病毒复制。
影响因子：
1.5
作者：
Mackewicz,C;Levy,JA
通讯作者：
Levy,JA
V3 变异性会影响抗体中和或增强 1 型人类免疫缺陷病毒不同毒株感染的能力。
DOI：
10.1073/pnas.90.24.11518
发表时间：
1993
影响因子：
11.1
作者：
Kliks,SC;Shioda,T;Haigwood,NL;Levy,JA
通讯作者：
Levy,JA
DOI：
10.1073/pnas.85.9.3198
发表时间：
1988-05
影响因子：
11.1
作者：
James R. Rusche;K. Javaherian;Charlene MCDANALt;J. Petro;Debra L. Lynn;R. Grimaila;Alphonse J. LANGLOISt;Robert C. Gallo;P. Fischinger;Dani P. BOLOGNESIt;SCOTr D. Putney;Thomas J. MATTHEWSt
通讯作者：
James R. Rusche;K. Javaherian;Charlene MCDANALt;J. Petro;Debra L. Lynn;R. Grimaila;Alphonse J. LANGLOISt;Robert C. Gallo;P. Fischinger;Dani P. BOLOGNESIt;SCOTr D. Putney;Thomas J. MATTHEWSt