Simplexvirus (taxid:10294)
VIRION

Enveloped, spherical to pleomorphic, 150-200 nm in diameter, T=16 icosahedral symmetry. The capsid consists of 162 capsomers and is surrounded by an amorphous tegument.
GENOME
Monopartite, linear, dsDNA genome of 152 kb. The genome contains terminal and internal reiterated sequences.
GENE EXPRESSION
All genes are transcribed by the host RNA polymerase II. and most mRNAs are unspliced. There are three temporal classes of genes: immediate-early (alpha), early (beta) and late (gamma). The immediate-early genes are transcribed immediately after infection to take control of cell defense and to activate early genes. These encode the proteins necessary for the viral DNA replication. The late genes mostly encode structural proteins. Latent genes can stop the replicative process at the early step. Certain proteins are downregulated translationaly by a leaky scanning from an upstream ORF.
ENZYMES
- DNA-dependent DNA polymerase [UL30]
- DNA primase [UL52]
- Tegument deneddylase (Peptidase C76) [UL36]
- Assemblin (Peptidase S21) [UL26]
- Kinase [UL13]
- Helicase [UL5]
- Endonuclease [UL41]
- Ribonucleoside-diphosphate reductase [UL40]
- Thymidine kinase [UL23]
- Uracil-DNA glycosylase [UL2]
REPLICATION
NUCLEAR
Lytic replication:
- Attachment of the viral gB, gC, gD and gH proteins to host receptors mediates endocytosis of the virus into the host cell.
- Fusion with the plasma membrane to release the core and the tegument proteins into the host cytoplasm.
- The capsid is transported to the nuclear pore where viral DNA is released into the nucleus.
- Transcription of immediate early genes which promote transcription of early genes and protect the virus against innate host immunity.
- Transcription of early viral mRNA by host polymerase II, encoding proteins involved in replication of the viral DNA.
- A first round of circular genome amplification occurs by bidirectional replication
- Synthesis of linear concatemer copies of viral DNA by rolling circle.
- Transcription of late mRNAs by host polymerase II, encoding structural proteins.
- Assembly of the virus in nuclear viral factories and budding through the inner lamella of the nuclear membrane which has been modified by the insertion of herpes glycoproteins, throughout the Golgi and final release at the plasma membrane.
Latent replication : replication of circular viral episome in tandem with the host cell DNA using the host cell replication machinery.
Host-virus interaction
Adaptive immune response inhibition
Herpes simplex protein US12 binds specifically to transporters associated with antigen processing (TAP), blocking peptide-binding to TAP and subsequent loading of peptides onto MHC class I molecules .
Herpes simplex virus 1 glycoprotein B and US3 collaborate to inhibit CD1d antigen presentation and NKT cell function
.
Apoptosis modulation
The viral kinase US3 modulates host apoptosis in different ways. It activates host protein kinase A/PKA to block apoptosis. Additionally, it also interacts with programmed cell death protein 4 (PDCD4) and retains it in the nucleus thereby inhibiting host apoptosis .
Autophagy modulation
Herpes simplex virus ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein and thus blocking host autophagy process .
Cell-cycle modulation
The viral proteins ICP27 and vhs act jointly to repress host gene transcription and blocks the cell cycle at the G1 phase . In addition the UL24 protein induces a cell cycle arrest at G2/M transition through inactivation of the host cyclinB/cdc2 complex
.
Innate immune response inhibition
Herpes simplex virus inhibits the cascade leading to production of interferon-beta by targeting different cellular proteins. ICP34.5 forms a complex with host TBK1 and thus disrupts the interaction of TBK1-containing complexes with IRF3
. Another viral protein, ICP0, prevents IRF3 activation and subsequent induction of IFN-beta expression
.
Host splicing inhibition
HSV-1 ICP27 is an alternative splicing regulator of host mRNA. It has been shown to act as a splicing silencer at the 3' splice site of the PML intron 7a .
Matching UniProtKB/Swiss-Prot entries
(all links/actions below point to uniprot.org website)230 entries grouped by protein
2 entries
Alkaline nuclease (EC 3.1.-.-)
2 entries
Cytoplasmic envelopment protein 1
2 entries
Cytoplasmic envelopment protein 2
3 entries
Cytoplasmic envelopment protein 3
2 entries
Capsid vertex component 1
2 entries
Capsid vertex component 2
6 entries
Major DNA-binding protein
6 entries
DNA polymerase catalytic subunit (EC 2.7.7.7) (EC 3.1.26.4)
2 entries
Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase)
5 entries
Envelope protein UL45 (18 kDa protein)
10 entries
Envelope glycoprotein B (gB)
5 entries
Envelope glycoprotein C
9 entries
Envelope glycoprotein D (gD)
4 entries
Envelope glycoprotein E (gE) (gE-1)
3 entries
Envelope glycoprotein G (gG) (gG-2)
4 entries
Envelope glycoprotein H (gH)
3 entries
Envelope glycoprotein I (gI)
2 entries
Envelope glycoprotein J
6 entries
Envelope glycoprotein K (Syncytial protein)
3 entries
Envelope glycoprotein L (gL)
2 entries
Envelope glycoprotein M (gM)
2 entries
Envelope glycoprotein N
2 entries
DNA replication helicase (EC 3.6.4.-)
2 entries
DNA helicase/primase complex-associated protein (HEPA) (Primase-associated factor)
2 entries
E3 ubiquitin-protein ligase ICP0 (EC 2.3.2.27) (Alpha-0 protein) (Immediate-early protein IE110) (RING-type E3 ubiquitin transferase ICP0) (Trans-acting transcriptional protein ICP0) (VMW110)
2 entries
E3 ubiquitin ligase ICP22 (Immediate-early protein IE68) (Infected cell protein 22) (ICP22)
3 entries
mRNA export factor (Immediate-early protein IE63) (Infected cell protein 27) (ICP27) (VMW63)
5 entries
Neurovirulence factor ICP34.5 (Infected cell protein 34.5) (protein gamma(1)34.5)
2 entries
Major viral transcription factor ICP4 (Alpha-4 protein) (Infected cell protein 4) (Transcriptional activator IE175)
5 entries
ICP47 protein (Immediate-early protein IE12) (Immediate-early-5) (Infected cell protein 47) (US12 protein) (Vmw12)
2 entries
Inner tegument protein
10 entries
Thymidine kinase (EC 2.7.1.21)
1 entry
Latency-related protein 1
1 entry
Latency-related protein 2
2 entries
Large tegument protein deneddylase (EC 3.4.19.12) (EC 3.4.22.-)
2 entries
Membrane protein UL43
2 entries
Major capsid protein (MCP)
2 entries
Nuclear egress protein 1
2 entries
Nuclear egress protein 2
4 entries
Nuclear phosphoprotein UL3
2 entries
Nuclear protein UL4
2 entries
Replication origin-binding protein (OBP) (OriBP)
2 entries
DNA polymerase processivity factor (DNA-binding protein UL42) (Polymerase accessory protein) (PAP)
2 entries
Portal protein
2 entries
DNA primase (EC 2.7.7.-)
3 entries
Ribonucleoside-diphosphate reductase large subunit (R1) (EC 1.17.4.1) (Ribonucleotide reductase large subunit)
4 entries
Ribonucleoside-diphosphate reductase small subunit (EC 1.17.4.1) (Ribonucleotide reductase small subunit)
3 entries
Accessory factor US11 (Vmw21)
2 entries
Capsid scaffolding protein (Capsid protein P40) (Protease precursor) (pPR) (Virion structural protein UL26)
2 entries
Small capsomere-interacting protein
5 entries
Virion host shutoff protein (Vhs) (EC 3.1.27.-)
3 entries
Tegument protein UL46 (Tegument protein VP11/12)
2 entries
Tegument protein UL14
3 entries
Tegument protein UL21
3 entries
Tegument protein UL47 (82/81 kDa tegument protein) (VMW82/81) (VP13/14)
3 entries
Tegument protein UL55
2 entries
Tegument protein UL51
5 entries
Tripartite terminase subunit 1
2 entries
Tripartite terminase subunit 2
2 entries
Tripartite terminase subunit 3 (EC 3.1.-.-) (Terminase large subunit)
4 entries
Triplex capsid protein 1
2 entries
Triplex capsid protein 2
2 entries
Serine/threonine-protein kinase UL13 (EC 2.7.11.1)
2 entries
Protein UL20
2 entries
Protein UL24
2 entries
Packaging protein UL32
3 entries
Protein UL56
3 entries
Uracil-DNA glycosylase (UDG) (EC 3.2.2.27) (UNG)
2 entries
Protein US2
2 entries
Serine/threonine-protein kinase US3 (EC 2.7.11.1)
3 entries
Virion protein US10
3 entries
Protein US8.5
3 entries
Envelope protein US9 (10 kDa protein)
1 entry
Envelope glycoprotein J
4 entries
Tegument protein VP16 (Alpha trans-inducing protein) (Alpha-TIF) (ICP25) (Vmw65)
2 entries
Tegument protein VP22
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Protein | ModelArchive |
ICP47 protein (Immediate-early protein IE12) (Immediate-early-5) (Infected cell protein 47) (US12 protein)... | ma-jd-viral-62159 |
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Protein | ModelArchive |
Envelope glycoprotein K (Syncytial protein) | ma-jd-viral-49381 |
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Protein | ModelArchive |
Envelope glycoprotein K (Syncytial protein) | ma-jd-viral-49381 |
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Protein | ModelArchive |
Virion host shutoff protein (Vhs) (EC 3.1.27.-) | ma-jd-viral-22425 |