Human cytomegalovirus serum neutralizing antibodies block virus infection of endothelial/epithelial cells, but not fibroblasts, early during primary infection
Human cytomegalovirus serum neutralizing antibodies block virus infection of endothelial/epithelial cells, but not fibroblasts, early during primary infection
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DOI：
10.1099/vir.0.83523-0
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发表时间：
2008-04-01
影响因子：
3.8
通讯作者：
Revello, M. Grazia
中科院分区：
文献类型：
--
作者：
Gerna, Giuseppe;Sarasini, Antonella;Revello, M. Grazia
一组人血清对在内皮（或上皮）细胞中繁殖和测试的人巨细胞病毒（HCMV）临床分离株表现出的中和效力比对感染人成纤维细胞的相同病毒高出≥1 28倍。在18例原发感染组中，感染后前3个月内，人成纤维细胞的反向几何平均滴度在10-15范围内，而内皮细胞感染中和活性在前10天内就已经存在，在发病后30、60和90天分别达到中位水平122、320和545，然后缓慢下降。这种差异也在大多数重新激活和远程 HCMV 感染以及超免疫球蛋白制剂中得到证实。对内皮/上皮细胞感染所需的 HCMV pUL131A、pUL130 和 pUL128 基因座产物的抗体反应为这种差异中和活性提供了潜在的分子基础。此外，针对 pUL131A、pUL130 和 pUL128 蛋白产生的单克隆/单特异性抗体被发现对 HCMV 斑块形成和来自 HCMV 感染细胞的 HCMV 白细胞转移具有抑制活性。因此，成纤维细胞中人血清中和活性的常规测定具有误导性。 pUL131A、pUL130 和 pUL128 的抗体似乎表现出主要的 HCMV 中和和传播抑制活性。
A panel of human sera exhibited a >= 1 28-fold higher neutralizing potency against a human cytomegalovirus (HCMV) clinical isolate propagated and tested in endothelial (or epithelial) cells than against the same virus infecting human fibroblasts. In a group of 18 primary infections, the reverse geometric mean titre was in the range of 10-15 in human fibroblasts within the first 3 months after the onset of infection, whereas the endothelial cell infection-neutralizing activity was already present within the first 10 days, reaching median levels of 122, 320 and 545 at respectively 30, 60 and 90 days after onset, then declining slowly. This difference was also confirmed in the majority of reactivated and remote HCMV infections, as well as in a hyperimmune globulin preparation. The antibody response to HCMV pUL131A, pUL130 and pUL128 locus products, which are required for endothelial/epithelial cell infection, provided a potential molecular basis for such a differential neutralizing activity. In addition, monoclonal/monospecific antibodies raised against the pUL131A, pUL130 and pUL128 proteins were found to display an inhibitory activity on HCMV plaque formation and HCMV leukocyte transfer from HCMV-infected cells. Hence, conventional determination of the neutralizing activity of human sera in fibroblasts is misleading. Antibodies to pUL131A, pUL130 and pUL128 appear to display a major HCMV-neutralizing and dissemination-inhibiting activity.