Localization of the WD Repeat-Containing Protein 5 to the Virion Assembly Compartment Facilitates Human Cytomegalovirus Assembly

We previously reported that human cytomegalovirus (HCMV) utilizes the cellular protein WD repeat-containing protein 5 (WDR5) to facilitate capsid nuclear egress. Here, we further show that HCMV infection results in WDR5 localization in a juxtanuclear region and that its localization to this cellular site is associated with viral replication and late viral gene expression. Furthermore, WDR5 accumulated in the virion assembly compartment (vAC) and colocalized with vAC markers of γ-tubulin, early endosomes, and viral vAC marker proteins pp65, pp28, and glycoprotein B (gB). WDR5 coimmunoprecipitated with multiple virion proteins, including major capsid protein (MCP), pp150, pp65, pIRS1, and pTRS1, which may explain WDR5 accumulation in the vAC during infection. WDR5 fractionated with virions in either the presence or absence of Triton X-100 and was present in purified viral particles, suggesting that WDR5 was incorporated into HCMV virions. Thus, WDR5 localized to the vAC and was incorporated into virions, raising the possibility that in addition to capsid nuclear egress, WDR5 could also participate in cytoplasmic HCMV virion morphogenesis. IMPORTANCE Human cytomegalovirus (HCMV) has a large (∼235-kb) genome that contains over 170 open reading frames (ORFs) and exploits numerous cellular factors to facilitate its replication. In the late phase of HCMV infection, cytoplasmic membranes are reorganized to establish the virion assembly compartment (vAC), which has been shown to be necessary for efficient assembly of progeny virions. We previously reported that WDR5 facilitates HCMV nuclear egress. Here, we show that WDR5 is localized to the vAC and incorporated into virions, perhaps contributing to efficient virion maturation. Thus, findings in this study identified a potential role for WDR5 in HCMV assembly in the cytoplasmic phase of virion morphogenesis.