Lymphocryptovirus

VIRION

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Enveloped, spherical to pleomorphic, 150-200 nm in diameter, T=16 icosahedral symmetry. Capsid consists of 162 capsomers and is surrounded by an amorphous tegument. Glycoproteins complexes are embedded in the lipid envelope.

GENOME

Monopartite, linear, dsDNA genome of about 180 kb. The genome contains terminal and internal reiterated sequences.

GENE EXPRESSION

Each viral transcript usually encodes a single protein and has a promoter/regulatory sequence, a TATA box, a transcription initiation site, a 5' leader sequence of 30-300 bp (not translated), a 3' untranslated sequence of 10-30 bp, and a poly A signal. There are many gene overlaps. There are only few spliced genes. Some of the expressed ORFs are antisense to each other. Some ORFs can be accessed from more than one promoter. There are some non-coding genes.

REPLICATION

NUCLEAR

Lytic replication:

  1. Attachment of the viral glycoproteins 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 the 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

Epstein-Barr virus protein BNLF2a inhibits host adaptive immune response by interacting with TAP1 and TAP2 and thus preventing TAP-mediated peptide transport and subsequent loading. The glycine-alanine repeat domain (GAr) of Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1) prevents major histocompatibility complex (MHC) class I-restricted presentation of EBNA1 epitopes to cytotoxic T cells.

Apoptosis modulation

Epstein-Barr viral protein BHRF1 is a viral homologue of the Bcl-2 oncogene that is able to protect cells from induced apoptosis. EBNA3C directly interacts with host Gemin3 and thereby blocks p53-mediated apoptosis .

Autophagy modulation

The viral Bcl-2 homolog BHRF1 in addition to prevent host cel death, may also control host autophagy .

Cell-cycle modulation

EBNA3C forms a complex with Cyclin D1 thereby facilitating the G1-S phase transition . Additionally, EBNA2 can affect activities of cell cycle regulators and retards cell cycle progression at G2/M phase. The conserved UL24 family of human alpha, beta and gamma herpesviruses induces a cell cycle arrest at G2/M transition through inactivation of the host cyclinB/cdc2 complex. EBV encodes an UL24 homolog termed BXRF1 that should perform this role .

Innate immune response inhibition

EBV inhibits the cascade leading to production of interferon-beta by targeting host IRF3 protein with the BGLF4 protein kinase that directly interacts with and inhibits host IRF3. BRLF1 expression also decreases induction of IFN-beta, and reduces expression of IRF3 and IRF7.

Host splicing inhibition

EBV EB2 modulates the host mRNA expression by exporting unspliced mRNA, thereby inducing alternative splicing .

Matching UniProtKB/Swiss-Prot entries

194 entries grouped by strain (browse by keywords)

76 entries

Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4) reference strain

Select_allDeselect_all
PRIM_EBVB9 DNA primase (EC 2.7.7.-)
RPMS1_EBVB9 Uncharacterized protein RPMS1
BRRF1_EBVB9 Transcriptional activator BRRF1
SCAF_EBVB9 Capsid scaffolding protein (Capsid protein P40) (Protease precursor) (pPR) (Protein EC-RF3/EC-RF3A) ...
RIR2_EBVB9 Ribonucleoside-diphosphate reductase small subunit (EC 1.17.4.1) (Ribonucleotide reductase small ...
UL32_EBVB9 Packaging protein UL32 homolog
TRX1_EBVB9 Triplex capsid protein 1
UL95_EBVB9 Protein BGLF3
RIR1_EBVB9 Ribonucleoside-diphosphate reductase large subunit (R1) (EC 1.17.4.1) (Ribonucleotide reductase ...
TEG7_EBVB9 Tegument protein UL51 homolog
LMP1_EBVB9 Latent membrane protein 1 (LMP-1) (Protein p63) [Cleaved into: Protein p25]
TRX2_EBVB9 Triplex capsid protein 2
SCP_EBVB9 Small capsomere-interacting protein
UL92_EBVB9 Uncharacterized protein BDLF4
UL87_EBVB9 TBP-like protein BcRF1
RTA_EBVB9 Replication and transcription activator (Rta) (Immediate-early protein Rta)
ICP27_EBVB9 mRNA export factor ICP27 homolog (Mta) (ORF57 protein homolog) (Protein SM)
MCP_EBVB9 Major capsid protein (MCP)
LMP2_EBVB9 Latent membrane protein 2 (Terminal protein)
NEC1_EBVB9 Nuclear egress protein 1
ITP_EBVB9 Inner tegument protein
GP42_EBVB9 Glycoprotein 42 (gp42) [Cleaved into: Soluble gp42]
EBNA1_EBVB9 Epstein-Barr nuclear antigen 1 (EBNA-1) (EBV nuclear antigen 1)
GB_EBVB9 Envelope glycoprotein B (gB)
GL_EBVB9 Envelope glycoprotein L (gL)
CVC2_EBVB9 Capsid vertex component 2
EBNA3_EBVB9 Epstein-Barr nuclear antigen 3 (EBNA-3) (EBV nuclear antigen 3) (Epstein-Barr nuclear antigen 3A) ...
BDLF2_EBVB9 Protein BDLF2
GP350_EBVB9 Envelope glycoprotein GP350 (Membrane antigen) (MA)
KR2_EBVB9 Serine/threonine-protein kinase BGLF4 (EC 2.7.11.1)
CEP1_EBVB9 Cytoplasmic envelopment protein 1
CEP3_EBVB9 Cytoplasmic envelopment protein 3
EAR_EBVB9 Apoptosis regulator BHRF1 (Early antigen protein R) (EA-R) (Nuclear antigen)
BILF2_EBVB9 Glycoprotein BILF2
BHLF1_EBVB9 Uncharacterized protein BHLF1
DNBI_EBVB9 Major DNA-binding protein
AN_EBVB9 Shutoff alkaline exonuclease (SOX) (EC 3.1.-.-)
BLLF2_EBVB9 Uncharacterized protein BLLF2
CEP2_EBVB9 Cytoplasmic envelopment protein 2
BFRF2_EBVB9 Uncharacterized protein BFRF2
BMRF2_EBVB9 Protein BMRF2
BDLF3_EBVB9 Glycoprotein BDLF3
BZLF1_EBVB9 Trans-activator protein BZLF1 (EB1) (Zebra)
BILF1_EBVB9 G-protein coupled receptor BILF1
BKRF4_EBVB9 Tegument protein BKRF4
BNL2B_EBVB9 Uncharacterized protein BNLF2b
LTP_EBVB9 Large tegument protein deneddylase (EC 3.4.19.12) (EC 3.4.22.-)
KITH_EBVB9 Thymidine kinase (EC 2.7.1.21)
EBNA2_EBVB9 Epstein-Barr nuclear antigen 2 (EBNA-2) (EBV nuclear antigen 2)
GH_EBVB9 Envelope glycoprotein H (gH)
LF1_EBVB9 Uncharacterized LF1 protein
DPOL_EBVB9 DNA polymerase catalytic subunit (EC 2.7.7.7)
DUT_EBVB9 Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase)
GM_EBVB9 Envelope glycoprotein M (gM)
GN_EBVB9 Envelope glycoprotein N
EBNA4_EBVB9 Epstein-Barr nuclear antigen 4 (EBNA-4) (EBV nuclear antigen 4) (Epstein-Barr nuclear antigen 3B) ...
EBNA5_EBVB9 Epstein-Barr nuclear antigen leader protein (EBNA-LP) (EBV nuclear antigen leader protein) ...
EBNA6_EBVB9 Epstein-Barr nuclear antigen 6 (EBNA-6) (EBV nuclear antigen 6) (Epstein-Barr nuclear antigen 3C) ...
EAD_EBVB9 DNA polymerase processivity factor BMRF1 (Early antigen protein D) (EA-D) (Polymerase accessory ...
BLRF2_EBVB9 Tegument protein BLRF2
BTRF1_EBVB9 Uncharacterized protein BTRF1
BALF1_EBVB9 Apoptosis regulator BALF1
BNL2A_EBVB9 Protein BNLF2a
BARF1_EBVB9 Secreted protein BARF1 (33 kDa early protein) (p33)
CVC1_EBVB9 Capsid vertex component 1
BRRF2_EBVB9 Tegument protein BRRF2
LF2_EBVB9 Protein LF2
PORTL_EBVB9 Portal protein
LF3_EBVB9 Uncharacterized protein LF3
MTP_EBVB9 Major tegument protein (MTP) (Protein p140)
NEC2_EBVB9 Nuclear egress protein 2
IL10H_EBVB9 Viral interleukin-10 homolog (vIL-10) (20 kDa protein) (Protein BCRF1)
UL24_EBVB9 Protein UL24 homolog
TRM1_EBVB9 Tripartite terminase subunit 1
UNG_EBVB9 Uracil-DNA glycosylase (UDG) (EC 3.2.2.27) (UNG)
TRM3_EBVB9 Tripartite terminase subunit 3 (EC 3.1.-.-) (Terminase large subunit)

56 entries

Epstein-Barr virus (strain AG876) (HHV-4) (Human herpesvirus 4) reference strain

Select_allDeselect_all
RIR2_EBVA8 Ribonucleoside-diphosphate reductase small subunit (EC 1.17.4.1) (Ribonucleotide reductase small ...
BRRF1_EBVA8 Transcriptional activator BRRF1
RTA_EBVA8 Replication and transcription activator (Rta) (Immediate-early protein Rta)
TEG7_EBVA8 Tegument protein UL51 homolog
RIR1_EBVA8 Ribonucleoside-diphosphate reductase large subunit (R1) (EC 1.17.4.1) (Ribonucleotide reductase ...
SCAF_EBVA8 Capsid scaffolding protein (Capsid protein P40) (Protease precursor) (pPR) (Protein EC-RF3/EC-RF3A) ...
KR2_EBVA8 Serine/threonine-protein kinase BGLF4 (EC 2.7.11.1)
PORTL_EBVA8 Portal protein
MCP_EBVA8 Major capsid protein (MCP)
KITH_EBVA8 Thymidine kinase (EC 2.7.1.21)
LMP1_EBVA8 Latent membrane protein 1 (LMP-1) (Protein p63)
NEC1_EBVA8 Nuclear egress protein 1
LF1_EBVA8 Uncharacterized LF1 protein
EAR_EBVA8 Apoptosis regulator BHRF1 (Early antigen protein R) (EA-R) (Nuclear antigen)
GP42_EBVA8 Glycoprotein 42 (gp42)
GM_EBVA8 Envelope glycoprotein M (gM)
ITP_EBVA8 Inner tegument protein
GB_EBVA8 Envelope glycoprotein B (gB)
IL10H_EBVA8 Viral interleukin-10 homolog (vIL-10) (20 kDa protein) (Protein BCRF1)
DNBI_EBVA8 Major DNA-binding protein
GL_EBVA8 Envelope glycoprotein L (gL)
BKRF4_EBVA8 Tegument protein BKRF4
EBNA2_EBVA8 Epstein-Barr nuclear antigen 2 (EBNA-2) (EBV nuclear antigen 2)
BRRF2_EBVA8 Tegument protein BRRF2
GP350_EBVA8 Envelope glycoprotein GP350 (Membrane antigen) (MA)
EBNA3_EBVA8 Epstein-Barr nuclear antigen 3 (EBNA-3) (EBV nuclear antigen 3) (Epstein-Barr nuclear antigen 3A) ...
EBNA4_EBVA8 Epstein-Barr nuclear antigen 4 (EBNA-4) (EBV nuclear antigen 4) (Epstein-Barr nuclear antigen 3B) ...
BLRF2_EBVA8 Tegument protein BLRF2
CEP3_EBVA8 Cytoplasmic envelopment protein 3
CVC2_EBVA8 Capsid vertex component 2
BMRF2_EBVA8 Protein BMRF2
BNL2A_EBVA8 Protein BNLF2a
BDLF2_EBVA8 Protein BDLF2
CEP1_EBVA8 Cytoplasmic envelopment protein 1
BZLF1_EBVA8 Trans-activator protein BZLF1 (EB1) (Zebra)
DPOL_EBVA8 DNA polymerase catalytic subunit (EC 2.7.7.7)
DUT_EBVA8 Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase)
BARF1_EBVA8 Secreted protein BARF1 (33 kDa early protein) (p33)
GN_EBVA8 Envelope glycoprotein N
GH_EBVA8 Envelope glycoprotein H (gH)
ICP27_EBVA8 mRNA export factor ICP27 homolog (Mta) (ORF57 protein homolog) (Protein SM)
LTP_EBVA8 Large tegument protein deneddylase (EC 3.4.19.12) (EC 3.4.22.-)
MTP_EBVA8 Major tegument protein (MTP) (Protein p140)
EBNA1_EBVA8 Epstein-Barr nuclear antigen 1 (EBNA-1) (EBV nuclear antigen 1)
EBNA5_EBVA8 Epstein-Barr nuclear antigen leader protein (EBNA-LP) (EBV nuclear antigen leader protein) ...
EBNA6_EBVA8 Epstein-Barr nuclear antigen 6 (EBNA-6) (EBV nuclear antigen 6) (Epstein-Barr nuclear antigen 3C) ...
EAD_EBVA8 DNA polymerase processivity factor BMRF1 (Early antigen protein D) (EA-D) (Polymerase accessory ...
BTRF1_EBVA8 Uncharacterized protein BTRF1
BNL2B_EBVA8 Uncharacterized protein BNLF2b
AN_EBVA8 Shutoff alkaline exonuclease (SOX) (EC 3.1.-.-)
CEP2_EBVA8 Cytoplasmic envelopment protein 2
BLLF2_EBVA8 Uncharacterized protein BLLF2
LMP2_EBVA8 Latent membrane protein 2 (Terminal protein)
LF2_EBVA8 Protein LF2
UL92_EBVA8 Uncharacterized protein BDLF4
TRM3_EBVA8 Tripartite terminase subunit 3 (EC 3.1.-.-) (Terminase large subunit)

3 entries

Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4)

Select_allDeselect_all
YBL2_EBVB9 Uncharacterized protein BBLF2
YEC4_EBVB9 Uncharacterized protein EC-RF4
HELI_EBVB9 DNA replication helicase (EC 3.6.4.-)

56 entries

Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4)

Select_allDeselect_all
BNL2A_EBVG Protein BNLF2a
RIR1_EBVG Ribonucleoside-diphosphate reductase large subunit (R1) (EC 1.17.4.1) (Ribonucleotide reductase ...
RTA_EBVG Replication and transcription activator (Rta) (Immediate-early protein Rta)
SCAF_EBVG Capsid scaffolding protein (Capsid protein P40) (Protease precursor) (pPR) (Protein EC-RF3/EC-RF3A) ...
RIR2_EBVG Ribonucleoside-diphosphate reductase small subunit (EC 1.17.4.1) (Ribonucleotide reductase small ...
TEG7_EBVG Tegument protein UL51 homolog
RPMS1_EBVG Uncharacterized protein RPMS1
MCP_EBVG Major capsid protein (MCP)
MTP_EBVG Major tegument protein (MTP) (Protein p140)
TRM3_EBVG Tripartite terminase subunit 3 (EC 3.1.-.-) (Terminase large subunit)
KR2_EBVG Serine/threonine-protein kinase BGLF4 (EC 2.7.11.1)
GP42_EBVG Glycoprotein 42 (gp42) [Cleaved into: Soluble gp42]
GB_EBVG Envelope glycoprotein B (gB)
GN_EBVG Envelope glycoprotein N
BKRF4_EBVG Tegument protein BKRF4
GM_EBVG Envelope glycoprotein M (gM)
BMRF2_EBVG Protein BMRF2
EBNA1_EBVG Epstein-Barr nuclear antigen 1 (EBNA-1) (EBV nuclear antigen 1)
DUT_EBVG Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase)
EBNA2_EBVG Epstein-Barr nuclear antigen 2 (EBNA-2) (EBV nuclear antigen 2)
GP350_EBVG Envelope glycoprotein GP350 (Membrane antigen) (MA)
EBNA3_EBVG Epstein-Barr nuclear antigen 3 (EBNA-3) (EBV nuclear antigen 3) (Epstein-Barr nuclear antigen 3A) ...
DPOL_EBVG DNA polymerase catalytic subunit (EC 2.7.7.7)
CEP1_EBVG Cytoplasmic envelopment protein 1
DNBI_EBVG Major DNA-binding protein
EAR_EBVG Apoptosis regulator BHRF1 (Early antigen protein R) (EA-R) (Nuclear antigen)
AN_EBVG Shutoff alkaline exonuclease (SOX) (EC 3.1.-.-)
BZLF1_EBVG Trans-activator protein BZLF1 (EB1) (Zebra)
BNL2B_EBVG Uncharacterized protein BNLF2b
CEP2_EBVG Cytoplasmic envelopment protein 2
BRRF2_EBVG Tegument protein BRRF2
BDLF2_EBVG Protein BDLF2
CVC2_EBVG Capsid vertex component 2
BLRF2_EBVG Tegument protein BLRF2
BARF1_EBVG Secreted protein BARF1 (33 kDa early protein) (p33)
LF1_EBVG Uncharacterized LF1 protein
ICP27_EBVG mRNA export factor ICP27 homolog (Mta) (ORF57 protein homolog) (Protein SM)
LF2_EBVG Protein LF2
GL_EBVG Envelope glycoprotein L (gL)
ITP_EBVG Inner tegument protein
GH_EBVG Envelope glycoprotein H (gH)
EBNA4_EBVG Epstein-Barr nuclear antigen 4 (EBNA-4) (EBV nuclear antigen 4) (Epstein-Barr nuclear antigen 3B) ...
EBNA5_EBVG Epstein-Barr nuclear antigen leader protein (EBNA-LP) (EBV nuclear antigen leader protein) ...
EBNA6_EBVG Epstein-Barr nuclear antigen 6 (EBNA-6) (EBV nuclear antigen 6) (Epstein-Barr nuclear antigen 3C) ...
EAD_EBVG DNA polymerase processivity factor BMRF1 (Early antigen protein D) (EA-D) (Polymerase accessory ...
BALF1_EBVG Apoptosis regulator BALF1
BRRF1_EBVG Transcriptional activator BRRF1
BLLF2_EBVG Uncharacterized protein BLLF2
BTRF1_EBVG Uncharacterized protein BTRF1
LMP1_EBVG Latent membrane protein 1 (LMP-1) (Protein p63)
LTP_EBVG Large tegument protein deneddylase (EC 3.4.19.12) (EC 3.4.22.-)
LMP2_EBVG Latent membrane protein 2 (Terminal protein)
IL10H_EBVG Viral interleukin-10 homolog (vIL-10) (20 kDa protein) (Protein BCRF1)
PORTL_EBVG Portal protein
LF3_EBVG Uncharacterized protein LF3
KITH_EBVG Thymidine kinase (EC 2.7.1.21)

1 entry

Epstein-Barr virus (strain Cao) (HHV-4) (Human herpesvirus 4)

LMP1_EBVC Latent membrane protein 1 (LMP-1) (Protein p63)

1 entry

Epstein-Barr virus (strain P3HR-1) (HHV-4) (Human herpesvirus 4)

VGP3_EBVP3 Envelope glycoprotein GP340 (Membrane antigen) (MA)

1 entry

Epstein-Barr virus (strain Raji) (HHV-4) (Human herpesvirus 4)

LMP1_EBVR Latent membrane protein 1 (LMP-1) (Protein p63)