Latent Cytomegalovirus-Driven Recruitment of Activated CD4+ T Cells Promotes Virus Reactivation.
Latent Cytomegalovirus-Driven Recruitment of Activated CD4+ T Cells Promotes Virus Reactivation.
复制标题
DOI：
10.3389/fimmu.2021.657945
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Wills MR
中科院分区：
文献类型：
--
作者：
Jackson SE;Chen KC;Groves IJ;Sedikides GX;Gandhi A;Houldcroft CJ;Poole EL;Montanuy I;Mason GM;Okecha G;Reeves MB;Sinclair JH;Wills MR
人类巨细胞病毒 (HCMV) 感染不会被最初的免疫反应清除，但会在宿主的一生中持续存在，部分原因是它能够在髓系细胞中建立潜伏感染。 HCMV 已被证明可以在裂解感染和潜伏感染期间操纵细胞蛋白的分泌。潜伏感染引起的变化主要在CD34+祖细胞中进行研究。虽然 CD34+ 细胞通常驻留在骨髓中，但它们的衍生 CD14+ 单核细胞会迁移到外周，并在那里短暂循环直至外渗到组织部位。我们分析了 HCMV 潜伏感染对 CD14+ 单核细胞分泌组的影响，发现 CD14+ 潜伏相关分泌组中 CCL8 和 CXCL10 趋化因子均上调。与 CD34+ 细胞不同，CD14+ 潜伏期相关分泌蛋白组不会诱导静息免疫细胞亚群的迁移，但会诱导以 CXCL10 依赖性方式表达 CXCR3 的活化 NK 和 T 细胞的迁移。正如 CD34+ 潜伏感染中报道的那样，CD14+ 潜伏相关的分泌组也抑制了受刺激的 CD4+ T 细胞的抗病毒活性。然而，令人惊讶的是，活化的自体 CD4+ T 细胞与潜伏感染的单核细胞共培养导致 HCMV 重新激活，其水平与使用 M-CSF 和 IL-1β 细胞因子观察到的水平相当。我们认为这些事件代表了一种潜在的策略，可以使 HCMV 重新激活并在外周组织部位进行病毒的局部传播。
Human cytomegalovirus (HCMV) infection is not cleared by the initial immune response but persists for the lifetime of the host, in part due to its ability to establish a latent infection in cells of the myeloid lineage. HCMV has been shown to manipulate the secretion of cellular proteins during both lytic and latent infection; with changes caused by latent infection mainly investigated in CD34+ progenitor cells. Whilst CD34+ cells are generally bone marrow resident, their derivative CD14+ monocytes migrate to the periphery where they briefly circulate until extravasation into tissue sites. We have analyzed the effect of HCMV latent infection on the secretome of CD14+ monocytes, identifying an upregulation of both CCL8 and CXCL10 chemokines in the CD14+ latency-associated secretome. Unlike CD34+ cells, the CD14+ latency-associated secretome did not induce migration of resting immune cell subsets but did induce migration of activated NK and T cells expressing CXCR3 in a CXCL10 dependent manner. As reported in CD34+ latent infection, the CD14+ latency-associated secretome also suppressed the anti-viral activity of stimulated CD4+ T cells. Surprisingly, however, co-culture of activated autologous CD4+ T cells with latently infected monocytes resulted in reactivation of HCMV at levels comparable to those observed using M-CSF and IL-1β cytokines. We propose that these events represent a potential strategy to enable HCMV reactivation and local dissemination of the virus at peripheral tissue sites.
登录
查看更多内容
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
DOI：
10.1073/pnas.95.7.3937
发表时间：
1998-03-31
影响因子：
11.1
作者：
Hahn, G;Jores, R;Mocarski, ES
通讯作者：
Mocarski, ES
影响因子：
5.4
作者：
Jackson, Sarah E.;Sedikides, George X.;Wills, Mark R.
通讯作者：
Wills, Mark R.
影响因子：
4.8
作者：
Dupont, Liane;Du, Lily;Reeves, Matthew B.
通讯作者：
Reeves, Matthew B.
影响因子：
7.3
作者：
Jackson SE;Sedikides GX;Okecha G;Poole EL;Sinclair JH;Wills MR
通讯作者：
Wills MR