The HCMV tegument protein UL47 forms a complex that functions during viral entry

Human cytomegalovirus (HCMV) is a β herpesvirus with the typical herpesvirus structure; the DNA genome is enclosed by an icosahedral capsid that is further surrounded by a layer of proteins (tegument) and a membrane envelope. The tegument layer of HCMV contains 20–25 virally encoded proteins that are able to act on the cell immediately after infection without prior protein synthesis. Some of the functions HCMV tegument proteins include transcriptional activation, cell cycle modulation, and immune evasion. However, very little is known about the majority of the HCMV tegument proteins. Since tegument proteins in other herpesviruses function during entry and egress, I postulated that HCMV tegument proteins would be required for these processes as well.; The best candidates for such proteins were UL47 and UL48 since their herpes simplex virus homologs are involved in viral DNA release, virion morphogenesis and egress. Labeled immunoprecipitations from cells infected with HCMV demonstrate that these two proteins coprecipitate with several other proteins. Immunoprecipitation-western blots of mock and infected cells lysates demonstrated that UL47, UL48, UL69 and the major capsid protein (MCP) are able to coprecipitate, suggesting that the four proteins form a complex at late times of infection.; By generating a virus (DUL47) that lacks UL47, I demonstrated that this protein is required for efficient HCMV replication in tissue culture. This growth defect is almost fully complemented by two different sets of complementing cells that express UL47 protein in trans and has been rescued by creation of a revertant virus (RUL47). The ΔUL47 mutant virus is less infectious than wild type and has a defect at early times of virus infection that results in a delay in the transcription of the viral immediate early genes. However, the virus is able to enter the cell and the capsid translocates to the nucleus with wild type kinetics. Thus our model for UL47 function is that UL47 or a UL47-containing complex is required for release of the viral DNA from the capsid at the nucleus of the infected cell.