Glycosylation of simian immunodeficiency virus influences immune-tissue targeting during primary infection, leading to immunodeficiency or viral control.
Glycosylation of simian immunodeficiency virus influences immune-tissue targeting during primary infection, leading to immunodeficiency or viral control.
复制标题
猿猴免疫缺陷病毒的糖基化会影响初次感染期间的免疫组织靶向，从而导致免疫缺陷或病毒控制。
DOI：
10.1128/jvi.00948-12
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发表时间：
2012
影响因子：
5.4
通讯作者：
Mori,Kazuyasu
中科院分区：
文献类型：
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作者：
Sugimoto,Chie;Nakamura,Shinichiro;Hagen,ShokoI;Tsunetsugu-Yokota,Yasuko;Villinger,Francois;Ansari,AftabA;Suzuki,Yasuo;Yamamoto,Naoki;Nagai,Yoshiyuki;Picker,LouisJ;Mori,Kazuyasu
人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）的聚糖在调节病毒-靶细胞相互作用中起着关键作用。我们以前曾报道，尽管SIVmac 239是致病性的，但其去糖基化的基本上非致病性的突变体（Δ5G）可用作减毒活疫苗，尽管两者在初次感染期间复制相似。这些发现促使我们确定这种两极分化的临床结果是否是由于这些病毒靶向的免疫组织的差异，其中存在功能和表型不同的记忆CD 4 +T细胞。结果显示，Δ5G在次级淋巴组织（ILT）中的复制水平比SIVmac 239低1至2个对数，而SIVmac 239感染但Δ 5G感染的动物消耗CXCR 3 + CCR 5+过渡记忆（TrM）CD 4 +T细胞。早期强大的Δ5G复制定位于小肠组织，特别是固有层（效应部位），而不是孤立的淋巴滤泡（诱导部位），并与CCR 6 + CXCR 3 − CCR 5+效应记忆CD 4 +T细胞的诱导和耗竭相关。这些结果表明，Env的差异糖基化决定了靶向的组织驻留CD 4 +T细胞的类型，这分别导致小肠中TrM-Th 1细胞的致病性感染和小肠中Th 17细胞的非致病性感染。
Glycans of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) play pivotal roles in modulating virus-target cell interactions. We have previously reported that, whereas SIVmac239 is pathogenic, its deglycosylated essentially nonpathogenic mutant (Δ5G) serves as a live-attenuated vaccine, although both replicate similarly during primary infection. These findings prompted us to determine whether such a polarized clinical outcome was due to differences in the immune tissues targeted by these viruses, where functionally and phenotypically different memory CD4+T cells reside. The results showed that Δ5G replicates in secondary lymphoid tissue (SLT) at 1- to 2-log-lower levels than SIVmac239, whereas SIVmac239-infected but not Δ5G-infected animals deplete CXCR3+CCR5+transitional memory (TrM) CD4+T cells. An early robust Δ5G replication was localized to small intestinal tissue, especially the lamina propria (effector site) rather than isolated lymphoid follicles (inductive site) and was associated with the induction and depletion of CCR6+CXCR3−CCR5+effector memory CD4+T cells. These results suggest that differential glycosylation of Env dictates the type of tissue-resident CD4+T cells that are targeted, which leads to pathogenic infection of TrM-Th1 cells in SLT and nonpathogenic infection of Th17 cells in the small intestine, respectively.