Complement-Opsonized HIV Modulates Pathways Involved in Infection of Cervical Mucosal Tissues: A Transcriptomic and Proteomic Study.

Complement-Opsonized HIV Modulates Pathways Involved in Infection of Cervical Mucosal Tissues: A Transcriptomic and Proteomic Study.
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补体的艾滋病毒调节涉及宫颈粘膜组织感染的途径:转录组和蛋白质组学研究。

DOI:
10.3389/fimmu.2021.625649
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发表时间:
2021
影响因子:
7.3
通讯作者:
Larsson M
Larsson M
中科院分区:
医学2区
文献类型:
--
作者:
Svanberg C;Ellegård R;Crisci E;Khalid M;Borendal Wodlin N;Svenvik M;Nyström S;Birse K;Burgener A;Shankar EM;Larsson M

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生殖器粘膜传播是艾滋病毒最常见的传播途径。据报道,病毒进入部位引发的初始反应受到宿主因素的影响,特别是该部位存在的补体成分,这将对艾滋病毒感染的结局和发病机制产生深远的影响。我们通过将宫颈活检组织暴露在游离或补体调理的HIV中来研究与宿主-病原体相互作用相关的初始事件。调理作用导致粘膜组织和迁徙的树突状细胞中HIV感染/获得率较高。转录组和蛋白质组学数据显示,与病毒复制相关的基因和蛋白以及参与病毒感染不同方面的途径明显更多和更高表达,包括干扰素信号、细胞因子谱和调理HIV的树突状细胞成熟。此外,蛋白质组学数据表明,艾滋病毒暴露总体上受到了抑制。这清楚地表明,HIV的调理作用改变了宫颈粘膜中的初始信号通路,促进了病毒的建立和感染。我们的发现为进一步研究这些早期HIV诱导事件在HIV发病机制中所起的作用提供了基础。
Genital mucosal transmission is the most common route of HIV spread. The initial responses triggered at the site of viral entry are reportedly affected by host factors, especially complement components present at the site, and this will have profound consequences on the outcome and pathogenesis of HIV infection. We studied the initial events associated with host-pathogen interactions by exposing cervical biopsies to free or complement-opsonized HIV. Opsonization resulted in higher rates of HIV acquisition/infection in mucosal tissues and emigrating dendritic cells. Transcriptomic and proteomic data showed a significantly more pathways and higher expression of genes and proteins associated with viral replication and pathways involved in different aspects of viral infection including interferon signaling, cytokine profile and dendritic cell maturation for the opsonized HIV. Moreover, the proteomics data indicate a general suppression by the HIV exposure. This clearly suggests that HIV opsonization alters the initial signaling pathways in the cervical mucosa in a manner that promotes viral establishment and infection. Our findings provide a foundation for further studies of the role these early HIV induced events play in HIV pathogenesis.
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