Journal article
Herpes Simplex Virus 1 UL34 Mutants That Affect Membrane Budding Regulation and Nuclear Lamina Disruption
Journal of virology, Vol.95(17), pp.e0087321-e0087321
08/10/2021
DOI: 10.1128/JVI.00873-21
PMCID: PMC8354240
PMID: 34133898
Abstract
Herpesvirus nuclear egress is a complex, regulated process coordinated by two virus proteins that are conserved among the herpesviruses that form a heterodimeric nuclear egress complex (NEC). The NEC drives budding of capsids at the inner nuclear membrane and recruits other viral and host cell proteins for disruption of the nuclear lamina, membrane scission, and fusion.
ABSTRACT
Nuclear envelope budding in herpesvirus nuclear egress may be negatively regulated, since the pUL31/pUL34 nuclear egress complex heterodimer can induce membrane budding without capsids when expressed ectopically or on artificial membranes
in vitro
, but not in the infected cell. We have previously described a pUL34 mutant that contained alanine substitutions at R158 and R161 and that showed impaired growth, impaired pUL31/pUL34 interaction, and unregulated budding. Here, we determine the phenotypic contributions of the individual substitutions to these phenotypes. Neither substitution alone was able to reproduce the impaired growth or nuclear egress complex (NEC) interaction phenotypes. Either substitution, however, could fully reproduce the unregulated budding phenotype, suggesting that misregulated budding may not substantially impair virus replication. In addition, the R158A substitution caused relocalization of the NEC to intranuclear punctate structures and recruited lamin A/C to these structures, suggesting that this residue might be important for recruitment of kinases for dispersal of nuclear lamins.
IMPORTANCE
Herpesvirus nuclear egress is a complex, regulated process coordinated by two virus proteins that are conserved among the herpesviruses that form a heterodimeric nuclear egress complex (NEC). The NEC drives budding of capsids at the inner nuclear membrane and recruits other viral and host cell proteins for disruption of the nuclear lamina, membrane scission, and fusion. The structural basis of individual activities of the NEC, apart from membrane budding, are not clear, nor is the basis of the regulation of membrane budding. Here, we explore the properties of NEC mutants that have an unregulated budding phenotype, determine the significance of that regulation for virus replication, and also characterize a structural requirement for nuclear lamina disruption.
Details
- Title: Subtitle
- Herpes Simplex Virus 1 UL34 Mutants That Affect Membrane Budding Regulation and Nuclear Lamina Disruption
- Creators
- Amber Vu - University of IowaShaowen White - Roy J. and Lucille A. Carver College of MedicineTiffany Cassmann - Roy J. and Lucille A. Carver College of MedicineRichard J. Roller - Roy J. and Lucille A. Carver College of Medicine
- Contributors
- Richard M. Longnecker (Editor)
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.95(17), pp.e0087321-e0087321
- DOI
- 10.1128/JVI.00873-21
- PMID
- 34133898
- PMCID
- PMC8354240
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R21AI133155; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: T32AI007533; DOI: 10.13039/100000001, name: National Science Foundation, award: DBI-1559927
- Language
- English
- Date published
- 08/10/2021
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics
- Record Identifier
- 9984297435802771
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