Nef alleles from children with non-progressive HIV-1 infection modulate MHC-II expression more efficiently than those from rapid progressors.
Nef alleles from children with non-progressive HIV-1 infection modulate MHC-II expression more efficiently than those from rapid progressors.
复制标题
来自非进展性 HIV-1 感染儿童的 Nef 等位基因比来自快速进展者的儿童更有效地调节 MHC-II 表达。
DOI：
10.1097/qad.0b013e32816aa37c
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Kirchhoff,Frank
中科院分区：
文献类型：
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作者：
Schindler,Michael;Wildum,Steffen;Casartelli,Nicoletta;Doria,Margherita;Kirchhoff,Frank
背景：它已经建立了缺陷nef基因和差异Nef介导的下调CD 4和MHC-I细胞表面表达可以与不同的速度的HIV-1疾病progress.Objective：评估是否nef等位基因来自围产期HIV-1感染的儿童显示没有，缓慢或快速的疾病进展不同的能力，以下调成熟的MHC-II或上调不变链（Ii）与不成熟的MHC-II complex.Methods：Nef等位基因来自HIV-1感染的儿童被克隆到表达载体和前病毒HIV-1构建体共表达Nef和增强的绿色荧光蛋白通过内部核糖体进入网站。Nef介导的CD 4、MHC-I、MHC-II或Ii表面表达的调节通过用水泡性口炎病毒G假型HIV-1 nef变体或瞬时转染的HeLa II类反式激活因子细胞转导的Jurkat T细胞、单核细胞THP-1细胞、CD 4 T细胞和巨噬细胞的流式细胞术分析来分析。来自非进展性感染的HIV-1感染儿童的Nef等位基因在Ii的上调和MHC-1的下调中明显更活跃。结论：在围产期HIV-1感染的非进展者中，Nef等位基因干扰MHC-II抗原呈递的频率高于快速进展者。可能在不成熟的宿主免疫系统的背景下，MHC-II功能的严重受损可能导致免疫激活水平降低和CD 4 T细胞的损失减缓。
Background:It has been established that defective nef genes and differences in the Nef-mediated downmodulation of CD4 and MHC-I cell surface expression can be associated with different rates of HIV-1 disease progression.Objective:To evaluate whether nef alleles derived from perinatally HIV-1-infected children showing no, slow or rapid disease progression differ in their abilities to downmodulate mature MHC-II or to upregulate the invariant chain (Ii) associated with immature MHC-II complexes.Methods:Nef alleles derived from HIV-1-infected children were cloned into expression vectors and proviral HIV-1 constructs co-expressing Nef and enhanced green fluorescence protein via an internal ribosomal entry site. Nef-mediated modulation of CD4, MHC-I, MHC-II or Ii surface expression was analysed by flow cytometric analysis of Jurkat T cells, monocytic THP-1 cells, CD4 T cells and macrophages transduced with vesicular stomatitis virus G-pseudotyped HIV-1 nef variants or transiently transfected HeLa class II transactivator cells.Results:Nef alleles derived from HIV-1-infected children with non-progressive infection were significantly more active in the upregulation of Ii and downregulation of MHC-II than those derived from rapid progressors.Conclusion:Nef alleles particularly active in interfering with MHC-II antigen presentation are more frequently found in perinatally HIV-1-infected non-progressors than rapid progressors. Possibly in the context of an immature host immune system, strongly impaired MHC-II function might contribute to lower levels of immune activation and a decelerated loss of CD4 T cells.