Varicella-zoster virus open reading frame 47 (ORF47) protein is critical for virus replication in dendritic cells and for spread to other cells.

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.