Antigenic variations in the CD4 induced sites of the CCR5-tropic, pathogenic SHIVSF162P3 gp120 variants
Antigenic variations in the CD4 induced sites of the CCR5-tropic, pathogenic SHIVSF162P3 gp120 variants
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DOI：
10.1034/j.1600-0684.2003.00027.x
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发表时间：
2003-08-01
影响因子：
0.7
通讯作者：
Chen-Mayer, C
中科院分区：
文献类型：
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作者：
Hsu, M;Buckner, C;Chen-Mayer, C
非致病性嗜CCR 5猿猴/人免疫缺陷病毒（SHIV）-SHIVSF 162的体内传代产生致病性分离株SHIVSF 162 P3。为了表征可能导致其致病性的包膜（Env）介导的特性，从SHIVSF 162 P3感染动物的血浆中克隆了主要（P3主要）和次要（P3次要）Env gp 120变体，并在荧光素酶报告病毒的背景下表达。与亲本SF 162相比，分析了由这些包膜介导的进入和对CD 4诱导位点（CD 4 i）抗体（MAb）中和的敏感性。序列分析显示，与SF 162相比，P3主要和次要变异体Envs分别包含14和17个氨基酸变化。由三种包膜介导的进入的等级顺序为P3主要> SF 162> P3次要，而观察到对CD 4 i MAb中和的敏感性的相反顺序。由于CD 4 i表位与辅助受体（CoR）结合位点重叠，这些发现表明SHIVSF 162体内传代后积累的氨基酸变化导致Env gp 120结构重排，从而调节CoR结合位点的暴露和/或构象。这反过来又导致P3主要变异体的进入和感染性增加，并可能部分负责SHIVSF 162 P3的致病性增强。
In vivo passage of non-pathogenic, CCR5-tropic simian/human immunodeficiency virus (SHIV) - SHIVSF162 resulted in a pathogenic isolate, SHIVSF162P3. In an attempt to characterize envelope (Env)-mediated properties that may contribute to its pathogenicity, major (P3 major) and minor (P3 minor) Env gp120 variants were cloned from the plasma of a SHIVSF162P3-infected animal, and expressed in the context of luciferase reporter viruses. Entry mediated by these envelopes and susceptibility to neutralization by CD4 induced-site (CD4i) antibodies (MAbs) was analyzed in comparison to parental SF162. Sequence analysis revealed that the P3 major and minor variant Envs contained 14 and 17 amino acid changes, respectively, compared with SF162. The rank order of entry mediated by the three envelopes was P3 major > SF162 > P3 minor, whereas the reverse order was observed for susceptibility to neutralization by CD4i MAbs. Since CD4i epitopes overlap the coreceptor (CoR) binding site, these findings suggest that the amino acid changes accumulated upon in vivo passage of SHIVSF162 result in Env gp120 structural rearrangements that modulate the exposure and/or conformation of the CoR binding site. This, in turn, led to increased entry and infectivity of the P3 major variant and may be responsible, in part, for the enhanced pathogenicity of SHIVSF162P3.