Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism
Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism
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DOI：
10.1073/pnas.0509201102
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发表时间：
2005-12-13
影响因子：
11.1
通讯作者：
Shenk, T
中科院分区：
文献类型：
--
作者：
Wang, D;Shenk, T
人巨细胞病毒可在多种不同的细胞类型中复制，包括上皮细胞、内皮细胞和成纤维细胞。然而，该病毒的实验室毒株已经失去了感染上皮细胞和内皮细胞的能力，其中许多毒株是通过在成纤维细胞中连续传代而开发出来的减毒疫苗候选株。由于UL131-UL128基因座的突变，它们的生长主要限于成纤维细胞。我们现在证明该基因的两个产物pUL130和pUL128与Gh和Gl形成络合物，但不与Go形成络合物。AD169实验室株缺乏功能性UL131蛋白，产生的病毒粒子只包含Gh-gl-go复合体。一种亲上皮和内皮细胞的AD169变异体，其中UL131 ORF已被修复，称为BADrUL131，产生携带Gh-gl-go和Gh-gl-pUL128-pUL130复合体的病毒粒子。抗pUL130和pUL128的抗体可阻断BADrUL131和融合诱导因子X临床分离株感染上皮细胞和内皮细胞，但不影响感染成纤维细胞的效率。
Human cytomegalovirus replicates in many different cell types, including epithelial cells, endothelial cells, and fibroblasts. However, laboratory strains of the virus, many of which were developed as attenuated vaccine candidates by serial passage in fibroblasts, have lost the ability to infect epithelial and endothelial cells. Their growth is restricted primarily to fibroblasts, due to mutations in the UL131-UL128 locus. We now demonstrate that two products of this locus, pUL130 and pUL128, form a complex with gH and gL, but not gO. The AD169 laboratory strain, which lacks a functional UL131 protein, produces virions containing only the gH-gL-gO complex. An epithelial and endothelial cell tropic AD169 variant in which the UL131 ORF has been repaired, termed BADrUL131, produces virions that carry both gH-gL-gO and gH-gL-pUL128-pUL130 complexes. Antibodies against pUL130 and pUL128 block infection of epithelial and endothelial cells by BADrUL131 and the fusion-inducing factor X clinical human cytomegalovirus isolate but do not affect the efficiency with which fibroblasts are infected.