A single point mutation in HIV-1 V3 loop alters the immunogenic properties of rgp120.
A single point mutation in HIV-1 V3 loop alters the immunogenic properties of rgp120.
复制标题
HIV-1 V3 环中的单点突变改变了 rgp120 的免疫原性特性。
DOI：
10.1007/s007050070041
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发表时间：
2000
影响因子：
2.7
通讯作者：
Boto,WM
中科院分区：
文献类型：
--
作者：
Lee,SK;Pestano,GA;Riley,J;Hasan,AS;Pezzano,M;Samms,M;Park,KJ;Guyden,J;Boto,WM
The results of the study presented in this report show that clones of env derived from genetically divergent HIV-1 field isolates fall into two major subsets based on the predicted secondary structure of the V3 region in gp120. One subset exemplified by the clones A-UG06c, B-RT3.12 and C-UG045 is predicted to assume a β-turn conformation in the V3 loop and comprises the GPG\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}\end{document} residues. The other subset exemplified by the clones D-UG23c and D-UG042 (G\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}\end{document}) are deficient in the expression of the β-turn in the loop. Since secondary conformations are highly likely to confer antigenic properties in a protein backbone at least for B cells, we have used nucleic acid immunization to test the effect of the β-turn deficiency on the immunogenic potential of rgp120 encoded in these field isolates. As hypothesized, inoculation of BALB/c mice with the env plasmid encoding the β-turn expressing rgp120 molecules resulted in the development of a vigorous antibody response to the homologous V3 loop peptides. In contrast, immunization with an rgp120 clone deficient in the β-turn in the V3 loop showed no evidence of antibody development to the V3 loop. Instead, the latter clones triggered T cell proliferative responses and markedly increased the level of IL-2 and IFN-γ production by T cells. Significantly, reconstitution of the β-turn conformation by site-directed mutagenesis of a single V3 loop residue yielded rgp120 molecules which restored antibody production while diminishing the cell-mediated immune (CMI) responses to the V3 residue. These observations demonstrate the marked impact of a single amino acid substitution on the immunogenic properties of V3 region in gp120 encoded by divergent HIV-1 field isolates.
