RT Journal Article
SR Electronic
T1 Human Cytomegalovirus Drives WDR5 to the Virion Assembly Compartment to Facilitate Virion Assembly
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.03.235630
DO 10.1101/2020.08.03.235630
A1 Bo Yang
A1 YongXuan Yao
A1 Hui Wu
A1 Hong Yang
A1 Xue-Hui Ma
A1 Dong Li
A1 Xian-Zhang Wang
A1 Sheng-Nan Huang
A1 Xuan Jiang
A1 Shuang Cheng
A1 Jin-Yan Sun
A1 Zhen-Li Huang
A1 CongJian Zhao
A1 Michael A. McVoy
A1 Jin-Hyun Ahn
A1 Wen-Bo Zeng
A1 Sitang Gong
A1 William J. Britt
A1 Min-Hua Luo
YR 2020
UL http://biorxiv.org/content/early/2020/08/04/2020.08.03.235630.abstract
AB We previously reported that human cytomegalovirus (HCMV) utilizes the cellular protein WDR5 to facilitate capsid nuclear egress. Here, we further show that HCMV infection drives WDR5 to the perinuclear region by a mechanism that requires viral replication and intact microtubules. WDR5 accumulated in the virion assembly compartment (vAC) and co-localized with vAC markers of gamma-tubulin (γ-tubulin), early endosomes, and viral vAC marker proteins pp65, pp28, and glycoprotein B (gB). WDR5 interacted with multiple virion proteins, including MCP, pp150, pp65, pIRS1, and pTRS1, which may explain the increasing WDR5 accumulation in the vAC during infection. WDR5 was then incorporated into HCMV virions and localized to the tegument layer, as demonstrated by fractionation and immune-gold electron microscopy. Thus, WDR5 is driven to the vAC and incorporated into virions, suggesting that WDR5 facilitates HCMV replication at later stage of virion assembly besides the capsid nuclear egress stage. These data highlight that WDR5 is a potential target for antiviral therapy.Importance Human cytomegalovirus (HCMV) has a large (~235-kb) genome that contains over 170 ORFs and exploits numerous cellular factors to facilitate its replication. In the late phase of HCMV infection cytoplasmic membranes are profoundly reconfigured to establish the virion assembly compartment (vAC), which is important for efficient assembly of progeny virions. We previously reported that WDR5 promotes HCMV nuclear egress. Here, we show that WDR5 is further driven to the vAC and incorporated into virions, perhaps to facilitate efficient virion maturation. This work identified potential roles for WDR5 in HCMV replication in the cytoplasmic stages of virion assembly. Taken together, WDR5 plays a critical role in HCMV capsid nuclear egress and is important for virion assembly, and thus is a potential target for antiviral treatment of HCMV-associated diseases.