Human Cytomegalovirus Nuclear Egress Complex Subunit, UL53, Associates with Capsids and Myosin Va, but Is Not Important for Capsid Localization towards the Nuclear Periphery

Wilkie, Adrian R.; Sharma, Madhu; Coughlin, Margaret; Pesola, Jean M.; Ericsson, Maria; Lawler, Jessica L.; Fernandez, Rosio; Coen, Donald M.

doi:10.3390/v14030479

Cited by 6 publications

(6 citation statements)

References 31 publications

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“…In addition, its binding to myosin Va was identified. Interestingly, further data led to the statement that pUL53 might not be important for capsid transition towards the nuclear periphery [ 37 ]. A very prominent host factor of the multicomponent NEC has been identified with the multi-ligand binding protein p32/gC1qR.…”

Section: Multiple Viral and Host Components Can Be Associated With Nu...mentioning

confidence: 99%

‘Come together’—The Regulatory Interaction of Herpesviral Nuclear Egress Proteins Comprises Both Essential and Accessory Functions

Häge

Marschall

2022

Cells

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Herpesviral nuclear egress is a fine-tuned regulatory process that defines the nucleocytoplasmic release of viral capsids. Nuclear capsids are unable to traverse via nuclear pores due to the fact of their large size; therefore, herpesviruses evolved to develop a vesicular transport pathway mediating the transition across the two leaflets of the nuclear membrane. The entire process involves a number of regulatory proteins, which support the local distortion of the nuclear envelope. In the case of the prototype species of β-Herpesvirinae, the human cytomegalovirus (HCMV), the nuclear egress complex (NEC) is determined by the core proteins pUL50 and pUL53 that oligomerize, form capsid docking lattices and mediate multicomponent assembly with NEC-associated viral and cellular proteins. The NEC-binding principle is based on the hook-into-groove interaction through an N-terminal hook-like pUL53 protrusion that embraces an α-helical pUL50 binding groove. Thus far, the function and characteristics of herpesviral core NECs have been well studied and point to the groove proteins, such as pUL50, as the multi-interacting, major determinants of NEC formation and egress. This review provides closer insight into (i) sequence and structure conservation of herpesviral core NEC proteins, (ii) experimentation on cross-viral core NEC interactions, (iii) the essential functional roles of hook and groove proteins for viral replication, (iv) an establishment of assay systems for NEC-directed antiviral research and (v) the validation of NEC as putative antiviral drug targets. Finally, this article provides new insights into the conservation, function and antiviral targeting of herpesviral core NEC proteins and, into the complex regulatory role of hook and groove proteins during the assembly, egress and maturation of infectious virus.

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Section: Multiple Viral and Host Components Can Be Associated With Nu...mentioning

confidence: 99%

‘Come together’—The Regulatory Interaction of Herpesviral Nuclear Egress Proteins Comprises Both Essential and Accessory Functions

Häge

Marschall

2022

Cells

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“…Interestingly, UL53 was observed directly on maturing capsids by immuno-gold staining (Milbradt et al, 2018), which led the authors to propose that capsid bound UL53 induces NEC lattice formation and primary envelopment (Figure 8). Recent work has validated this observation and shown that capsid bound UL53 does not influence capsid localisation to the nuclear membrane (Wilkie et al, 2022). This model is further supported by the observation that the HSV-1 homologue of UL53 recruits the UL50 homologue into complexes, but is dispensable for membrane remodelling in vitro (Lorenz et al, 2015).…”

Section: Stage 8: Nuclear Egressmentioning

confidence: 65%

The human cytomegalovirus decathlon: Ten critical replication events provide opportunities for restriction

Turner

Mathias²

2022

Front. Cell Dev. Biol.

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Human cytomegalovirus (HCMV) is a ubiquitous human pathogen that can cause severe disease in immunocompromised individuals, transplant recipients, and to the developing foetus during pregnancy. There is no protective vaccine currently available, and with only a limited number of antiviral drug options, resistant strains are constantly emerging. Successful completion of HCMV replication is an elegant feat from a molecular perspective, with both host and viral processes required at various stages. Remarkably, HCMV and other herpesviruses have protracted replication cycles, large genomes, complex virion structure and complicated nuclear and cytoplasmic replication events. In this review, we outline the 10 essential stages the virus must navigate to successfully complete replication. As each individual event along the replication continuum poses as a potential barrier for restriction, these essential checkpoints represent potential targets for antiviral development.

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“…Transmission and immunoelectron microscopy were performed as we described (Wilkie et al, 2022). Briefly, subconfluent human iPSCs (clone A4), LTC-hPGCLCs derived from them, and human NCCIT embryonal carcinoma cell lines were fixed with 4% paraformaldehyde and 0.1% glutaraldehyde in PBS and subjected to the standard transmission electron microscopy with negative staining using uranyl formate.…”

Section: Methodsmentioning

confidence: 99%

Viral proteins and virus-like particles of the LTR5_Hs endogenous retrovirus in human primordial germ cell-like cells

Kobayashi

Kreuzer

et al. 2022

Preprint

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The hominoid-specific endogenous retrovirus LTR5_Hs is transcriptionally activated in human primordial germ cell-like cells (hPGCLCs), a pluripotent stem cell-derived cell culture model of PGCs. Here, taking the unique advantage of our novel cell culture method to obtain large amounts of pure hPGCLCs, we performed proteomics profiling of hPGCLCs and detected various viral proteins produced from the LTR5_Hs RNA via ribosomal frameshifting. We also present transmission electron microscopy images of 100-nm diameter virus-like particles (VLPs) assembled at the surface of hPGCLCs. Compared to hPGCLCs, expression of LTR5_Hs RNA is far weaker in human seminomas, the germ cell tumors resembling PGCs. Re-analysis of published single cell RNA-seq data of human embryos revealed strong activation of LTR5_Hs in migrating PGCs but suppressed in PGCs upon they reach the gonadal anlagen. In the microfluidics-supported polarized embryoids mimicking peri-implantation stages of human embryos, LTR5_Hs RNA was detected by RNA in situ hybridization in NANOG+/TFAP2C+/SOX17+ cells resembling freshly emerged PGCs. These results support that human germ cells produce LTR5_Hs proteins and VLPs during their earliest stages of normal development until their settlement in the gonadal anlagen.

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Human Cytomegalovirus Nuclear Egress Complex Subunit, UL53, Associates with Capsids and Myosin Va, but Is Not Important for Capsid Localization towards the Nuclear Periphery

Cited by 6 publications

References 31 publications

‘Come together’—The Regulatory Interaction of Herpesviral Nuclear Egress Proteins Comprises Both Essential and Accessory Functions

‘Come together’—The Regulatory Interaction of Herpesviral Nuclear Egress Proteins Comprises Both Essential and Accessory Functions

The human cytomegalovirus decathlon: Ten critical replication events provide opportunities for restriction

Viral proteins and virus-like particles of the LTR5_Hs endogenous retrovirus in human primordial germ cell-like cells

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