Journal article
Cell Culture Evolution of a Herpes Simplex Virus 1 (HSV-1)/Varicella-Zoster Virus (VZV) UL34/ORF24 Chimeric Virus Reveals Novel Functions for HSV Genes in Capsid Nuclear Egress
Journal of virology, Vol.95(23), pp.e0095721-e0095721
11/09/2021
DOI: 10.1128/JVI.00957-21
PMCID: PMC8577396
PMID: 34523964
Abstract
Interactions among virus proteins are critical for assembly and egress of virus particles, and such interactions are attractive targets for antiviral therapy. Identification of critical functional interactions can be slow and tedious.
ABSTRACT
Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are both members of the alphaherpesvirus subfamily but belong to different genera. Substitution of the HSV-1 UL34 coding sequence with that of its VZV homolog, open reading frame 24 (ORF24), results in a virus that has defects in viral growth, spread, capsid egress, and nuclear lamina disruption very similar to those seen in a UL34-null virus despite normal interaction between ORF24 protein and HSV pUL31 and proper localization of the nuclear egress complex at the nuclear envelope. Minimal selection for growth in cell culture resulted in viruses that grew and spread much more efficiently that the parental chimeric virus. These viruses varied in their ability to support nuclear lamina disruption, normal nuclear egress complex localization, and capsid de-envelopment. Single mutations that suppress the growth defect were mapped to the coding sequences of ORF24, ICP22, and ICP4, and one virus carried single mutations in each of the ICP22 and US3 coding sequences. The phenotypes of these viruses support a role for ICP22 in nuclear lamina disruption and a completely unexpected role for the major transcriptional regulator, ICP4, in capsid nuclear egress.
IMPORTANCE
Interactions among virus proteins are critical for assembly and egress of virus particles, and such interactions are attractive targets for antiviral therapy. Identification of critical functional interactions can be slow and tedious. Capsid nuclear egress of herpesviruses is a critical event in the assembly and egress pathway and is mediated by two proteins, pUL31 and pUL34, that are conserved among herpesviruses. Here, we describe a cell culture evolution approach to identify other viral gene products that functionally interact with pUL34.
Details
- Title: Subtitle
- Cell Culture Evolution of a Herpes Simplex Virus 1 (HSV-1)/Varicella-Zoster Virus (VZV) UL34/ORF24 Chimeric Virus Reveals Novel Functions for HSV Genes in Capsid Nuclear Egress
- Creators
- Richard J. Roller - Roy J. and Lucille A. Carver College of MedicineTineke Hassman - Roy J. and Lucille A. Carver College of MedicineAlison Haugo-Crooks - University of Iowa
- Contributors
- Felicia Goodrum (Editor)
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.95(23), pp.e0095721-e0095721
- DOI
- 10.1128/JVI.00957-21
- PMID
- 34523964
- PMCID
- PMC8577396
- 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: R21AI148831; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R21153683
- Language
- English
- Date published
- 11/09/2021
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297321802771
Metrics
8 Record Views