当前位置: X-MOL 学术Viruses › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Herpes Simplex Virus Type-2 Paralyzes the Function of Monocyte-Derived Dendritic Cells.
Viruses ( IF 3.8 ) Pub Date : 2020-01-16 , DOI: 10.3390/v12010112
Linda Grosche 1 , Petra Mühl-Zürbes 1 , Barbara Ciblis 1 , Adalbert Krawczyk 2, 3 , Christine Kuhnt 1 , Lisa Kamm 1 , Alexander Steinkasserer 1 , Christiane Silke Heilingloh 1, 2
Affiliation  

Herpes simplex viruses not only infect a variety of different cell types, including dendritic cells (DCs), but also modulate important cellular functions in benefit of the virus. Given the relevance of directed immune cell migration during the initiation of potent antiviral immune responses, interference with DC migration constitutes a sophisticated strategy to hamper antiviral immunity. Notably, recent reports revealed that HSV-1 significantly inhibits DC migration in vitro. Thus, we aimed to investigate whether HSV-2 also modulates distinct hallmarks of DC biology. Here, we demonstrate that HSV-2 negatively interferes with chemokine-dependent in vitro migration capacity of mature DCs (mDCs). Interestingly, rather than mediating the reduction of the cognate chemokine receptor expression early during infection, HSV-2 rapidly induces β2 integrin (LFA-1)-mediated mDC adhesion and thereby blocks mDC migration. Mechanistically, HSV-2 triggers the proteasomal degradation of the negative regulator of β2 integrin activity, CYTIP, which causes the constitutive activation of LFA-1 and thus mDC adhesion. In conclusion, our data extend and strengthen recent findings reporting the reduction of mDC migration in the context of a herpesviral infection. We thus hypothesize that hampering antigen delivery to secondary lymphoid organs by inhibition of mDC migration is an evolutionary conserved strategy among distinct members of Herpesviridae.

中文翻译:


2 型单纯疱疹病毒使单核细胞衍生的树突状细胞的功能瘫痪。



单纯疱疹病毒不仅感染多种不同的细胞类型,包括树突状细胞(DC),而且还调节重要的细胞功能以利于病毒。鉴于定向免疫细胞迁移在强效抗病毒免疫反应启动过程中的相关性,干扰 DC 迁移构成了阻碍抗病毒免疫的复杂策略。值得注意的是,最近的报告表明 HSV-1 在体外显着抑制 DC 迁移。因此,我们的目的是研究 HSV-2 是否也调节 DC 生物学的独特特征。在这里,我们证明 HSV-2 会负面干扰成熟 DC (mDC) 的趋化因子依赖性体外迁移能力。有趣的是,HSV-2 不是在感染早期介导同源趋化因子受体表达的减少,而是迅速诱导 β2 整合素 (LFA-1) 介导的 mDC 粘附,从而阻止 mDC 迁移。从机制上讲,HSV-2 触发 β2 整合素活性负调节因子 CYTIP 的蛋白酶体降解,从而导致 LFA-1 的组成型激活,从而导致 mDC 粘附。总之,我们的数据扩展并强化了最近的研究结果,报告了在疱疹病毒感染的情况下 mDC 迁移减少。因此,我们假设通过抑制 mDC 迁移来阻碍抗原递送至次级淋巴器官是疱疹病毒科不同成员之间的进化保守策略。
更新日期:2020-01-16
down
wechat
bug