UL82 virion protein activates expression of immediate early viral genes in human cytomegalovirus-infected cells
UL82 virion protein activates expression of immediate early viral genes in human cytomegalovirus-infected cells
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DOI：
10.1073/pnas.97.26.14506
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发表时间：
2000-12-19
影响因子：
11.1
通讯作者：
Shenk, TE
中科院分区：
文献类型：
--
作者：
Bresnahan, WA;Shenk, TE
人巨细胞病毒UL 82基因编码定位于病毒颗粒的被膜结构域中的蛋白质（pp 71）。UL 82基因产物在感染时被递送到细胞核，并且被认为在基因激活中起作用。我们已经构建了一个人巨细胞病毒突变体，ADsubUL 82，缺乏一个实质性的一部分UL 82编码区。它在表达UL 82基因产物的人二倍体成纤维细胞上繁殖，并且可以通过在正常的非互补成纤维细胞上传代病毒原液一个生长周期来产生缺乏UL 82蛋白的突变病毒。UL 82缺陷型突变体在正常人成纤维细胞中表现出增殖依赖性生长缺陷。在低输入多重性（每个细胞0.01-0.1空斑形成单位）下，ADsubUL 82的生长受到严重限制，与野生型病毒相比，产量降低约10（5）倍。在较高的输入多重性（每个细胞10个噬斑形成单位）下，ADsubUL 82的生长几乎与野生型病毒一样好。通过使用人巨细胞病毒基因阵列，我们证明了UL 82的功能，以促进病毒mRNA的积累非常早的人巨细胞病毒复制周期。与UL 82突变体相关的生长表型似乎是由于其不能有效地激活人巨细胞病毒立即早期基因。
The human cytomegalovirus UL82 gene encodes a protein (pp71) that is localized in the tegument domain of the virus particle. The UL82 gene product is delivered to the nucleus at the time of infection, and it is believed to function in gene activation. We have constructed a human cytomegalovirus mutant, ADsubUL82, that lacks a substantial portion of the UL82 coding region. It was propagated on human diploid fibroblasts expressing the UL82 gene product, and it was possible to produce a mutant virus lacking the UL82 protein by passaging virus stocks for one cycle of growth on normal, noncomplementing fibroblasts. The UL82-deficient mutant displays a multiplicity-dependent growth defect in normal human fibroblasts. The growth of ADsubUL82 is severely restricted at low input multiplicities (0.01-0.1 plaque-forming units per cell), producing a yield that is reduced by a factor of about 10(5) in comparison to wild-type virus. At higher input multiplicities (10 plaque-forming units per cell), ADsubUL82 grew nearly as well as the wild-type virus. By using a human cytomegalovirus gene array, we demonstrated that UL82 functions to facilitate virus mRNA accumulation very early during the human cytomegalovirus replication cycle. The growth phenotype associated with the UL82 mutant seems to result from its inability to efficiently activate human cytomegalovirus immediate early genes.