当前位置: X-MOL 学术Med. Microbiol. Immunol. › 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.)
Transmission of cell-associated human cytomegalovirus isolates between various cell types using polymorphonuclear leukocytes as a vehicle
Medical Microbiology and Immunology ( IF 5.5 ) Pub Date : 2021-06-06 , DOI: 10.1007/s00430-021-00713-6
Berenike Braun 1 , Christian Sinzger 1
Affiliation  

Polymorphonuclear leukocytes (PMNs) are regarded as vehicles for the hematogenous dissemination of human cytomegalovirus (HCMV). In cell culture, this concept has been validated with cell-free laboratory strains but not yet with clinical HCMV isolates that grow strictly cell-associated. We, therefore, aimed to evaluate whether PMNs can also transmit such isolates from initially infected fibroblasts to other cell types, which might further clarify the role of PMNs in HCMV dissemination and provide a model to search for potential inhibitors. PMNs, which have been isolated from HCMV-seronegative individuals, were added for 3 h to fibroblasts infected with recent cell-associated HCMV isolates, then removed and transferred to various recipient cell cultures. The transfer efficiency in the recipient cultures was evaluated by immunofluorescence staining of viral immediate early antigens. Soluble derivatives of the cellular HCMV entry receptor PDGFRα were analyzed for their potential to interfere with this transfer. All of five tested HCMV isolates could be transferred to fibroblasts, endothelial and epithelial cells with transfer rates ranging from 2 to 9%, and the transferred viruses could spread focally in these recipient cells within 1 week. The PDGFRα-derived peptides IK40 and GT40 reduced transfer by 40 and 70% when added during the uptake step. However, when added during the transfer step, only IK40 was effective, inhibiting transmission by 20% on endothelial cells and 50–60% on epithelial cells and fibroblasts. These findings further corroborate the assumption of cell-associated HCMV dissemination by PMNs and demonstrate that it is possible to inhibit this transmission mode.



中文翻译:

使用多形核白细胞作为载体在各种细胞类型之间传播细胞相关的人巨细胞病毒分离株

多形核白细胞 (PMN) 被认为是人类巨细胞病毒 (HCMV) 血行传播的载体。在细胞培养中,这一概念已在无细胞实验室菌株中得到验证,但尚未在严格与细胞相关的临床 HCMV 分离株中得到验证。因此,我们旨在评估 PMN 是否也可以将此类分离物从最初感染的成纤维细胞传播到其他细胞类型,这可能进一步阐明 PMN 在 HCMV 传播中的作用,并提供一个模型来寻找潜在的抑制剂。从 HCMV 血清阴性个体中分离出的 PMN 被添加到感染了最近细胞相关 HCMV 分离株的成纤维细胞中 3 小时,然后移除并转移到各种受体细胞培养物中。通过病毒立即早期抗原的免疫荧光染色评估受体培养物中的转移效率。分析了细胞 HCMV 进入受体 PDGFRα 的可溶性衍生物干扰这种转移的潜力。所有五个测试的 HCMV 分离株都可以转移到成纤维细胞、内皮细胞和上皮细胞,转移率范围为 2% 到 9%,并且转移的病毒可以在 1 周内在这些受体细胞中局部传播。在摄取步骤中添加时,PDGFRα 衍生肽 IK40 和 GT40 将转移减少了 40% 和 70%。然而,当在转移步骤中加入时,只有 IK40 是有效的,对内皮细胞的传播抑制了 20%,对上皮细胞和成纤维细胞的传播抑制了 50-60%。

更新日期:2021-06-07
down
wechat
bug