Herpesvirus Nuclear Egress across the Outer Nuclear Membrane
Herpesvirus capsids are assembled in the nucleus and undergo a two-step process to cross the nuclear envelope. Capsids bud into the inner nuclear membrane (INM) aided by the nuclear egress complex (NEC) proteins UL31/34. At that stage of egress, enveloped virions are found for a short time in the pe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/12/2356 |
| _version_ | 1797499953494360064 |
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| author | Richard J. Roller David C. Johnson |
| author_facet | Richard J. Roller David C. Johnson |
| author_sort | Richard J. Roller |
| collection | DOAJ |
| description | Herpesvirus capsids are assembled in the nucleus and undergo a two-step process to cross the nuclear envelope. Capsids bud into the inner nuclear membrane (INM) aided by the nuclear egress complex (NEC) proteins UL31/34. At that stage of egress, enveloped virions are found for a short time in the perinuclear space. In the second step of nuclear egress, perinuclear enveloped virions (PEVs) fuse with the outer nuclear membrane (ONM) delivering capsids into the cytoplasm. Once in the cytoplasm, capsids undergo re-envelopment in the Golgi/trans-Golgi apparatus producing mature virions. This second step of nuclear egress is known as de-envelopment and is the focus of this review. Compared with herpesvirus envelopment at the INM, much less is known about de-envelopment. We propose a model in which de-envelopment involves two phases: (i) fusion of the PEV membrane with the ONM and (ii) expansion of the fusion pore leading to release of the viral capsid into the cytoplasm. The first phase of de-envelopment, membrane fusion, involves four herpes simplex virus (HSV) proteins: gB, gH/gL, gK and UL20. gB is the viral fusion protein and appears to act to perturb membranes and promote fusion. gH/gL may also have similar properties and appears to be able to act in de-envelopment without gB. gK and UL20 negatively regulate these fusion proteins. In the second phase of de-envelopment (pore expansion and capsid release), an alpha-herpesvirus protein kinase, US3, acts to phosphorylate NEC proteins, which normally produce membrane curvature during envelopment. Phosphorylation of NEC proteins reverses tight membrane curvature, causing expansion of the membrane fusion pore and promoting release of capsids into the cytoplasm. |
| first_indexed | 2024-03-10T03:54:52Z |
| format | Article |
| id | doaj.art-240cb7605756475a862b816fdf9af65d |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T03:54:52Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-240cb7605756475a862b816fdf9af65d2023-11-23T10:56:45ZengMDPI AGViruses1999-49152021-11-011312235610.3390/v13122356Herpesvirus Nuclear Egress across the Outer Nuclear MembraneRichard J. Roller0David C. Johnson1Microbiology & Immunology, University of Iowa, Iowa City, IA 52242, USAMolecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USAHerpesvirus capsids are assembled in the nucleus and undergo a two-step process to cross the nuclear envelope. Capsids bud into the inner nuclear membrane (INM) aided by the nuclear egress complex (NEC) proteins UL31/34. At that stage of egress, enveloped virions are found for a short time in the perinuclear space. In the second step of nuclear egress, perinuclear enveloped virions (PEVs) fuse with the outer nuclear membrane (ONM) delivering capsids into the cytoplasm. Once in the cytoplasm, capsids undergo re-envelopment in the Golgi/trans-Golgi apparatus producing mature virions. This second step of nuclear egress is known as de-envelopment and is the focus of this review. Compared with herpesvirus envelopment at the INM, much less is known about de-envelopment. We propose a model in which de-envelopment involves two phases: (i) fusion of the PEV membrane with the ONM and (ii) expansion of the fusion pore leading to release of the viral capsid into the cytoplasm. The first phase of de-envelopment, membrane fusion, involves four herpes simplex virus (HSV) proteins: gB, gH/gL, gK and UL20. gB is the viral fusion protein and appears to act to perturb membranes and promote fusion. gH/gL may also have similar properties and appears to be able to act in de-envelopment without gB. gK and UL20 negatively regulate these fusion proteins. In the second phase of de-envelopment (pore expansion and capsid release), an alpha-herpesvirus protein kinase, US3, acts to phosphorylate NEC proteins, which normally produce membrane curvature during envelopment. Phosphorylation of NEC proteins reverses tight membrane curvature, causing expansion of the membrane fusion pore and promoting release of capsids into the cytoplasm.https://www.mdpi.com/1999-4915/13/12/2356de-envelopmentphosphorylationnuclear envelopment complexmembrane fusionhemi-fusion |
| spellingShingle | Richard J. Roller David C. Johnson Herpesvirus Nuclear Egress across the Outer Nuclear Membrane Viruses de-envelopment phosphorylation nuclear envelopment complex membrane fusion hemi-fusion |
| title | Herpesvirus Nuclear Egress across the Outer Nuclear Membrane |
| title_full | Herpesvirus Nuclear Egress across the Outer Nuclear Membrane |
| title_fullStr | Herpesvirus Nuclear Egress across the Outer Nuclear Membrane |
| title_full_unstemmed | Herpesvirus Nuclear Egress across the Outer Nuclear Membrane |
| title_short | Herpesvirus Nuclear Egress across the Outer Nuclear Membrane |
| title_sort | herpesvirus nuclear egress across the outer nuclear membrane |
| topic | de-envelopment phosphorylation nuclear envelopment complex membrane fusion hemi-fusion |
| url | https://www.mdpi.com/1999-4915/13/12/2356 |
| work_keys_str_mv | AT richardjroller herpesvirusnuclearegressacrosstheouternuclearmembrane AT davidcjohnson herpesvirusnuclearegressacrosstheouternuclearmembrane |