Max von Pettenkofer-Institut, Lehrstuhl Virologie, Feodor-Lynen Strasse 25, D-81377 Munich, Germany. .
J Virol. 2010 May;84(9):4469-80. doi: 10.1128/JVI.02441-09. Epub 2010 Feb 24.
The glycoprotein gO (UL74) of human cytomegalovirus (HCMV) forms a complex with gH/gL. Virus mutants with a deletion of gO show a defect in secondary envelopment with the consequence that virus spread is restricted to a cell-associated pathway. Here we report that the positional homolog of HCMV gO, m74 of mouse CMV (MCMV), codes for a glycosylated protein which also forms a complex with gH (M75). m74 knockout mutants of MCMV show the same spread phenotype as gO knockout mutants of HCMV, namely, a shift from supernatant-driven to cell-associated spread. We could show that this phenotype is due to a reduction of infectious virus particles in cell culture supernatants. m74 knockout mutants enter fibroblasts via an energy-dependent and pH-sensitive pathway, whereas in the presence of an intact m74 gene product, entry is neither energy dependent nor pH sensitive. This entry phenotype is shared by HCMV expressing or lacking gO. Our data indicate that the m74 and UL74 gene products both codetermine CMV spread and CMV entry into cells. We postulate that MCMV, like HCMV, expresses alternative gH/gL complexes which govern cell-to-cell spread of the virus.
人巨细胞病毒（HCMV）的糖蛋白 gO（UL74）与 gH/gL 形成复合物。缺失 gO 的病毒突变体在二次包被过程中出现缺陷，结果病毒传播仅限于细胞相关途径。在这里，我们报告 HCMV gO 的位置同源物，即小鼠 CMV（MCMV）的 m74，编码一种糖基化蛋白，它也与 gH（M75）形成复合物。MCMV 的 m74 敲除突变体显示出与 HCMV 的 gO 敲除突变体相同的传播表型，即从上清液驱动的传播转变为细胞相关的传播。我们可以证明这种表型是由于细胞培养上清液中感染性病毒颗粒的减少。m74 敲除突变体通过能量依赖性和 pH 敏感途径进入成纤维细胞，而在完整的 m74 基因产物存在的情况下，进入既不是能量依赖性的，也不是 pH 敏感的。HCMV 表达或缺乏 gO 时都具有这种进入表型。我们的数据表明，m74 和 UL74 基因产物共同决定了 CMV 的传播和进入细胞。我们推测，MCMV 像 HCMV 一样，表达替代的 gH/gL 复合物，这些复合物控制病毒的细胞间传播。
