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.


Monopartite, linear, dsDNA genome of 152 kb. The genome contains terminal and internal reiterated sequences.


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.



Lytic replication:

  1. Attachment of the viral gB, gC, gD and gH proteins to host receptors mediates endocytosis of the virus into the host cell.
  2. Fusion with the plasma membrane to release the core and the tegument proteins into the host cytoplasm.
  3. The capsid is transported to the nuclear pore where viral DNA is released into the nucleus.
  4. Transcription of immediate early genes which promote transcription of early genes and protect the virus against innate host immunity.
  5. Transcription of early viral mRNA by host polymerase II, encoding proteins involved in replication of the viral DNA.
  6. A first round of circular genome amplification occurs by bidirectional replication
  7. Synthesis of linear concatemer copies of viral DNA by rolling circle.
  8. Transcription of late mRNAs by host polymerase II, encoding structural proteins.
  9. 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

230 entries grouped by strain (browse by keywords)

All proteins are shown (view only 146 complete proteome entries)

73 entries

Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) reference strain

Select_all Deselect_all  
AN_HHV11Alkaline nuclease (EC 3.1.-.-)
CEP1_HHV11Cytoplasmic envelopment protein 1
CEP2_HHV11Cytoplasmic envelopment protein 2
CEP3_HHV11Cytoplasmic envelopment protein 3
CVC1_HHV11Capsid vertex component 1
CVC2_HHV11Capsid vertex component 2
DNBI_HHV11Major DNA-binding protein
DPOL_HHV11DNA polymerase catalytic subunit (EC (EC
DUT_HHV11Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) (EC (dUTP ...
EV45_HHV11Envelope protein UL45 (18 kDa protein)
GB_HHV11Envelope glycoprotein B (gB)
GC_HHV11Envelope glycoprotein C
GD_HHV11Envelope glycoprotein D (gD)
GE_HHV11Envelope glycoprotein E (gE) (gE-1)
GG_HHV11Envelope glycoprotein G (gG) (gG-1)
GH_HHV11Envelope glycoprotein H (gH)
GI_HHV11Envelope glycoprotein I (gI)
GJ_HHV11Envelope glycoprotein J
GK_HHV11Envelope glycoprotein K (Syncytial protein)
GL_HHV11Envelope glycoprotein L (gL)
GM_HHV11Envelope glycoprotein M (gM)
GN_HHV11Envelope glycoprotein N
HELI_HHV11DNA replication helicase (EC 3.6.4.-)
HEPA_HHV11DNA helicase/primase complex-associated protein (HEPA) (Primase-associated ...
ICP0_HHV11E3 ubiquitin-protein ligase ICP0 (EC (Alpha-0 protein) ...
ICP22_HHV11Transcriptional regulator ICP22 (Immediate-early protein IE68) (Infected cell ...
ICP27_HHV11mRNA export factor (Immediate-early protein IE63) (Infected cell protein 27) ...
ICP34_HHV11Neurovirulence factor ICP34.5 (Infected cell protein 34.5) (protein ...
ICP47_HHV11ICP47 protein (Immediate-early protein IE12) (Immediate-early-5) (Infected cell ...
ICP4_HHV11Major viral transcription factor ICP4 (Alpha-4 protein) (Infected cell protein ...
ITP_HHV11Inner tegument protein
KITH_HHV11Thymidine kinase (EC
LTP_HHV11Large tegument protein deneddylase (EC (EC 3.4.22.-)
MB43_HHV11Membrane protein UL43
MCP_HHV11Major capsid protein (MCP)
NEC1_HHV11Nuclear egress protein 1
NEC2_HHV11Nuclear egress protein 2
NP03_HHV11Nuclear phosphoprotein UL3
NP04_HHV11Nuclear protein UL4
OBP_HHV11Replication origin-binding protein (OBP) (OriBP)
PAP_HHV11DNA polymerase processivity factor (DNA-binding protein UL42) (Polymerase ...
PORTL_HHV11Portal protein
PRIM_HHV11DNA primase (EC 2.7.7.-)
RIR1_HHV11Ribonucleoside-diphosphate reductase large subunit (R1) (EC ...
RIR2_HHV11Ribonucleoside-diphosphate reductase small subunit (EC ...
RNB_HHV11RNA-binding protein (Vmw21)
SCAF_HHV11Capsid scaffolding protein (Capsid protein P40) (Protease precursor) (pPR) ...
SCP_HHV11Small capsomere-interacting protein
SHUT_HHV11Virion host shutoff protein (Vhs) (EC 3.1.27.-)
TEG1_HHV11Tegument protein UL46 (Tegument protein VP11/12)
TEG3_HHV11Tegument protein UL14
TEG4_HHV11Tegument protein UL21
TEG5_HHV11Tegument protein UL47 (82/81 kDa tegument protein) (VMW82/81) (VP13/14)
TEG6_HHV11Tegument protein UL55
TEG7_HHV11Tegument protein UL51
TRM1_HHV11Tripartite terminase subunit 1
TRM2_HHV11Tripartite terminase subunit 2
TRM3_HHV11Tripartite terminase subunit 3 (EC 3.1.-.-) (Terminase large subunit)
TRX1_HHV11Triplex capsid protein 1
TRX2_HHV11Triplex capsid protein 2
UL13_HHV11Serine/threonine-protein kinase UL13 (EC (Virion protein VMW57)
UL20_HHV11Protein UL20
UL24_HHV11Protein UL24
UL32_HHV11Packaging protein UL32
UL56_HHV11Protein UL56
UNG_HHV11Uracil-DNA glycosylase (UDG) (EC (UNG)
US02_HHV11Protein US2
US03_HHV11Serine/threonine-protein kinase US3 (EC
US10_HHV11Virion protein US10
US8A_HHV11Protein US8.5
US9_HHV11Envelope protein US9 (10 kDa protein)
VP16_HHV11Tegument protein VP16 (Alpha trans-inducing protein) (Alpha-TIF) (ICP25) (Vmw65)
VP22_HHV11Tegument protein VP22

72 entries

Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2) reference strain

Select_all Deselect_all  
CEP1_HHV2HCytoplasmic envelopment protein 1
CEP2_HHV2HCytoplasmic envelopment protein 2
CEP3_HHV2HCytoplasmic envelopment protein 3
CVC1_HHV2HCapsid vertex component 1
CVC2_HHV2HCapsid vertex component 2
DNBI_HHV2HMajor DNA-binding protein
DPOL_HHV2HDNA polymerase catalytic subunit (EC (EC
DUT_HHV2HDeoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) (EC (dUTP ...
EV45_HHV2HEnvelope protein UL45 (18 kDa protein)
GB_HHV2HEnvelope glycoprotein B (gB)
GC_HHV2HEnvelope glycoprotein C
GD_HHV2HEnvelope glycoprotein D (gD)
GE_HHV2HEnvelope glycoprotein E (gE) (gE-2)
GG_HHV2HEnvelope glycoprotein G (gG) (gG-2)
GH_HHV2HEnvelope glycoprotein H (gH)
GI_HHV2HEnvelope glycoprotein I (gI)
GJ_HHV2HEnvelope glycoprotein J
GK_HHV2HEnvelope glycoprotein K (Syncytial protein)
GL_HHV2HEnvelope glycoprotein L (gL)
GM_HHV2HEnvelope glycoprotein M (gM)
GN_HHV2HEnvelope glycoprotein N
HELI_HHV2HDNA replication helicase (EC 3.6.4.-)
HEPA_HHV2HDNA helicase/primase complex-associated protein (HEPA) (Primase-associated ...
ICP0_HHV2HE3 ubiquitin-protein ligase ICP0 (EC (RING-type E3 ubiquitin ...
ICP22_HHV2HTranscriptional regulator ICP22 (Immediate-early protein IE68) (Infected cell ...
ICP27_HHV2HmRNA export factor (Immediate-early protein IE63) (Infected cell protein 27) ...
ICP34_HHV2HNeurovirulence factor ICP34.5 (Infected cell protein 34.5) (protein ...
ICP47_HHV2HICP47 protein (Immediate-early protein IE12) (Immediate-early-5) (Infected cell ...
ICP4_HHV2HMajor viral transcription factor ICP4 homolog (Alpha-4 protein) (Infected cell ...
ITP_HHV2HInner tegument protein
KITH_HHV2HThymidine kinase (EC
LTP_HHV2HLarge tegument protein deneddylase (EC (EC 3.4.22.-)
MB43_HHV2HMembrane protein UL43
MCP_HHV2HMajor capsid protein (MCP)
NEC1_HHV2HNuclear egress protein 1
NEC2_HHV2HNuclear egress protein 2
NP03_HHV2HNuclear phosphoprotein UL3
NP04_HHV2HNuclear protein UL4
OBP_HHV2HReplication origin-binding protein (OBP) (OriBP)
PAP_HHV2HDNA polymerase processivity factor (DNA-binding protein UL42) (Polymerase ...
PORTL_HHV2HPortal protein
PRIM_HHV2HDNA primase (EC 2.7.7.-)
RIR1_HHV2HRibonucleoside-diphosphate reductase large subunit (R1) (EC ...
RIR2_HHV2HRibonucleoside-diphosphate reductase small subunit (EC ...
RNB_HHV2HProbable RNA-binding protein
SCAF_HHV2HCapsid scaffolding protein (Capsid protein P40) (Protease precursor) (pPR) ...
SCP_HHV2HSmall capsomere-interacting protein
SHUT_HHV2HVirion host shutoff protein (Vhs) (EC 3.1.27.-)
TEG1_HHV2HTegument protein UL46 (Tegument protein VP11/12)
TEG3_HHV2HTegument protein UL14
TEG4_HHV2HTegument protein UL21
TEG5_HHV2HTegument protein UL47 (82/81 kDa tegument protein) (VMW82/81) (VP13/14)
TEG6_HHV2HTegument protein UL55
TEG7_HHV2HTegument protein UL51
TRM1_HHV2HTripartite terminase subunit 1
TRM2_HHV2HTripartite terminase subunit 2
TRM3_HHV2HTripartite terminase subunit 3 (EC 3.1.-.-) (Terminase large subunit)
TRX1_HHV2HTriplex capsid protein 1
TRX2_HHV2HTriplex capsid protein 2
UL13_HHV2HSerine/threonine-protein kinase UL13 (EC
UL20_HHV2HProtein UL20
UL24_HHV2HProtein UL24
UL32_HHV2HPackaging protein UL32
UL56_HHV2HProtein UL56
UNG_HHV2HUracil-DNA glycosylase (UDG) (EC (UNG)
US02_HHV2HProtein US2
US03_HHV2HSerine/threonine-protein kinase US3 (EC
US10_HHV2HVirion protein US10
US8A_HHV2HProtein US8.5
US9_HHV2HEnvelope protein US9 (10 kDa protein)
VP16_HHV2HTegument protein VP16 (Alpha trans-inducing protein) (Alpha-TIF) (ICP25) (Vmw65)
VP22_HHV2HTegument protein VP22

15 entries

Human herpesvirus 1 (strain F) (HHV-1) (Human herpes simplex virus 1)

Select_all Deselect_all  
DNBI_HHV1FMajor DNA-binding protein
GB_HHV1FEnvelope glycoprotein B (gB)
GD_HHV1FEnvelope glycoprotein D (gD)
GE_HHV1FEnvelope glycoprotein E (gE) (gE-1)
GH_HHV1FEnvelope glycoprotein H (gH)
ICP34_HHV1FNeurovirulence factor ICP34.5 (Infected cell protein 34.5) (protein ...
LRP1_HHV1FLatency-related protein 1
LRP2_HHV1FLatency-related protein 2
NP03_HHV1FNuclear phosphoprotein UL3
TEG1_HHV1FTegument protein UL46 (Tegument protein VP11/12)
TEG5_HHV1FTegument protein UL47 (82/81 kDa tegument protein) (VMW82/81) (VP13/14)
TRM1_HHV1FTripartite terminase subunit 1
US10_HHV1FVirion protein US10
US8A_HHV1FUS8.5 protein
VP16_HHV1FTegument protein VP16 (Alpha trans-inducing protein) (Alpha-TIF) (ICP25) (Vmw65)

12 entries

Human herpesvirus 1 (strain KOS) (HHV-1) (Human herpes simplex virus 1)

Select_all Deselect_all  
CEP3_HHV1KCytoplasmic envelopment protein 3
DNBI_HHV1KMajor DNA-binding protein
DPOL_HHV1KDNA polymerase catalytic subunit (EC (EC
EV45_HHV1KEnvelope protein UL45 (18 kDa protein)
GB_HHV1KEnvelope glycoprotein B (gB)
GC_HHV1KEnvelope glycoprotein C
GD_HHV1KEnvelope glycoprotein D (gD)
GK_HHV1KEnvelope glycoprotein K (Syncytial protein)
GL_HHV1KEnvelope glycoprotein L (gL)
KITH_HHV1KThymidine kinase (EC
RIR2_HHV1KRibonucleoside-diphosphate reductase small subunit (EC ...
SHUT_HHV1KVirion host shutoff protein (Vhs) (EC 3.1.27.-)

12 entries

Human herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2)

Select_all Deselect_all  
EV45_HHV23Envelope protein UL45 (18 kDa protein)
GB_HHV23Envelope glycoprotein B (gB)
GC_HHV23Envelope glycoprotein C
GD_HHV23Envelope glycoprotein D (gD)
GI_HHV23Envelope glycoprotein I (gI)
KITH_HHV23Thymidine kinase (EC
NP03_HHV23Nuclear phosphoprotein UL3
RIR1_HHV23Ribonucleoside-diphosphate reductase large subunit (R1) (EC ...
RIR2_HHV23Ribonucleoside-diphosphate reductase small subunit (EC ...
SHUT_HHV23Virion host shutoff protein (Vhs) (EC 3.1.27.-)
UNG_HHV23Uracil-DNA glycosylase (UDG) (EC (UNG)
VP16_HHV23Tegument protein VP16 (Alpha trans-inducing protein) (Alpha-TIF) (ICP25) (Vmw65)

6 entries

Human herpesvirus 1 (strain HFEM) (HHV-1) (Human herpes simplex virus 1)

Select_all Deselect_all  
GH_HHV1EEnvelope glycoprotein H (gH)
ICP27_HHV1EmRNA export factor (Immediate-early protein IE63) (Infected cell protein 27) ...
KITH_HHV1EThymidine kinase (EC
TEG4_HHV1ETegument protein UL21
TEG6_HHV1ETegument protein UL55
UL56_HHV1EProtein UL56

4 entries

Cercopithecine herpesvirus 1 (CeHV-1) (Simian herpes B virus)

Select_all Deselect_all  
GD_CHV1Envelope glycoprotein D (gD)
GE_CHV1Envelope glycoprotein E (gE)
US9_CHV1Envelope protein US9 homolog (10 kDa protein)
VGLJ_CHV1Envelope glycoprotein J

3 entries

Bovine herpesvirus 2 (strain BMV) (BoHV-2) (Bovine mammillitis virus)

Select_all Deselect_all  
DNBI_BHV2BMajor DNA-binding protein
GB_BHV2BEnvelope glycoprotein B (gB)
TRM1_BHV2BTripartite terminase subunit 1

3 entries

Human herpesvirus 1 (strain Angelotti) (HHV-1) (Human herpes simplex virus 1)

Select_all Deselect_all  
DPOL_HHV1ADNA polymerase catalytic subunit (EC (EC
GD_HHV1AEnvelope glycoprotein D (gD)
TRM1_HHV1ATripartite terminase subunit 1

3 entries

Human herpesvirus 1 (strain MP) (HHV-1) (Human herpes simplex virus 1)

Select_all Deselect_all  
EV45_HHV1MEnvelope protein UL45 (18 kDa protein)
GK_HHV1MEnvelope glycoprotein K (Syncytial protein)
RNB_HHV1MRNA-binding protein (Vmw21)

3 entries

Human herpesvirus 2 (strain G) (HHV-2) (Human herpes simplex virus 2)

Select_all Deselect_all  
GC_HHV2GEnvelope glycoprotein C (Glycoprotein F)
SHUT_HHV2GVirion host shutoff protein (Vhs) (EC 3.1.27.-)
TRX1_HHV2GTriplex capsid protein 1

2 entries

Herpes simplex virus type 2 (strain SA8) (Simian agent 8)

Select_all Deselect_all  
GB_HSV2SEnvelope glycoprotein B (gB)
ICP47_HSV2SICP47 protein (Immediate-early protein IE12) (Immediate-early-5) (Infected cell ...

2 entries

Human herpesvirus 1 (strain Patton) (HHV-1) (Human herpes simplex virus 1)

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GB_HHV1PEnvelope glycoprotein B (gB)
GD_HHV1PEnvelope glycoprotein D (gD)

2 entries

Human herpesvirus 1 (strain SC16) (HHV-1) (Human herpes simplex virus 1)

Select_all Deselect_all  
DPOL_HHV1SDNA polymerase catalytic subunit (EC (EC
KITH_HHV1SThymidine kinase (EC

2 entries

Human herpesvirus 2 (HHV-2) (Human herpes simplex virus 2)

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AN_HHV2Alkaline nuclease (EC 3.1.-.-)
DNBI_HHV2Major DNA-binding protein

2 entries

Saimiriine herpesvirus 1 (strain MV-5-4-PSL) (SaHV-1) (Marmoset herpesvirus)

Select_all Deselect_all  
GB_SHV1Envelope glycoprotein B (gB)
KITH_SHV1Thymidine kinase (EC

1 entry

Bovine herpesvirus 2 (strain BHM-1) (BoHV-2) (Bovine mammillitis virus)

KITH_BHV2HThymidine kinase (EC

1 entry

Cercopithecine herpesvirus 1 (strain E2490) (CeHV-1) (Simian herpes B virus)

ICP47_CHV1EICP47 protein (Immediate-early protein IE12) (Immediate-early-5) (Infected cell ...

1 entry

Cercopithecine herpesvirus 16 (CeHV-16) (Herpesvirus papio 2)

ICP47_CHV16ICP47 protein (Immediate-early protein IE12) (Immediate-early-5) (Infected cell ...

1 entry

Herpesvirus ateles type 1 (strain Lennette)

GB_HSVA1Envelope glycoprotein B (gB)

1 entry

Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1)

KITH_HHV1Thymidine kinase (EC

1 entry

Human herpesvirus 1 (strain A44) (HHV-1) (Human herpes simplex virus 1)

TRX1_HHV14Triplex capsid protein 1

1 entry

Human herpesvirus 1 (strain CL101) (HHV-1) (Human herpes simplex virus 1)

KITH_HHV1CThymidine kinase (EC

1 entry

Human herpesvirus 1 (strain CVG-2) (HHV-1) (Human herpes simplex virus 1)

ICP34_HHV1DNeurovirulence factor ICP34.5 (Infected cell protein 34.5) (protein ...

1 entry

Human herpesvirus 1 (strain HZT) (HHV-1) (Human herpes simplex virus 1)

GD_HHV1HEnvelope glycoprotein D (gD)

1 entry

Human herpesvirus 1 (strain MGH-10) (HHV-1) (Human herpes simplex virus 1)

ICP34_HHV1NNeurovirulence factor ICP34.5 (Infected cell protein 34.5) (protein ...

1 entry

Human herpesvirus 1 (strain R15) (HHV-1) (Human herpes simplex virus 1)

GK_HHV1REnvelope glycoprotein K (Syncytial protein)

1 entry

Human herpesvirus 1 (strain R19) (HHV-1) (Human herpes simplex virus 1)

GK_HHV19Envelope glycoprotein K (Syncytial protein)

1 entry

Human herpesvirus 2 (strain 186) (HHV-2) (Human herpes simplex virus 2)

DPOL_HHV21DNA polymerase catalytic subunit (EC (EC

1 entry

Human herpesvirus 2 (strain B4327UR) (HHV-2) (Human herpes simplex virus 2)

GG_HHV2BEnvelope glycoprotein G (gG) (gG-2)