Hu Huiling, Cohen Jeffrey I
Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Virology. 2005 Jul 5;337(2):304-11. doi: 10.1016/j.virol.2005.04.024.
Varicella-zoster virus infects human dendritic cells (DCs). We found that VZV infection of DCs resulted in down-regulation of Fas expression on the surface of cells. VZV ORF47 was critical for replication of virus in human immature, but not mature DCs. Immature DCs infected with a mutant virus unable to express ORF47 expressed similar levels of a VZV immediate-early protein as cells infected with parental virus; however, cells infected with the ORF47 mutant expressed lower levels of glycoprotein E. Thus, in the absence of ORF47 protein, there is a block in viral replication between immediate-early and late gene expression. VZV unable to express ORF47 was severely impaired for spread of virus from DCs to melanoma cells. Infection of DCs with parental VZV resulted in a different pattern of phosphoproteins compared with the ORF47 mutant virus. Thus, VZV ORF47 is important for replication in immature DCs and for spread to other cells.
水痘带状疱疹病毒感染人类树突状细胞(DCs)。我们发现,DCs受到水痘带状疱疹病毒感染会导致细胞表面Fas表达下调。水痘带状疱疹病毒开放阅读框47(VZV ORF47)对于病毒在人类未成熟而非成熟DCs中的复制至关重要。感染了无法表达ORF47的突变病毒的未成熟DCs,其水痘带状疱疹病毒立即早期蛋白的表达水平与感染亲本病毒的细胞相似;然而,感染ORF47突变体的细胞糖蛋白E的表达水平较低。因此,在缺乏ORF47蛋白的情况下,病毒在立即早期和晚期基因表达之间的复制存在障碍。无法表达ORF47的水痘带状疱疹病毒从DCs传播至黑色素瘤细胞的能力严重受损。与ORF47突变病毒相比,亲本水痘带状疱疹病毒感染DCs会导致不同的磷酸化蛋白模式。因此,VZV ORF47对于在未成熟DCs中的复制以及向其他细胞的传播很重要。