Lymphocryptovirus (taxid:10375)

Lymphocryptovirus is a genus of dsDNA viruses in the Herpesviridae family that infect many mammals, including humans. Human herpesvirus 4 (formerly called Epstein-Barr virus (EBV) is responsible for mononucleosis in humans.

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.
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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.

ENZYMES

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

(all links/actions below point to uniprot.org website)

194 entries grouped by strain

78 entries

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

Select_allDeselect_all
LTP_EBVB9 Large tegument protein deneddylase (EC 3.4.19.12) (EC 3.4.22.-)
GB_EBVB9 Envelope glycoprotein B (gB)
EAD_EBVB9 DNA polymerase processivity factor BMRF1 (Early Antigen Diffused) (EA-D) (Polymerase accessory ...
GP350_EBVB9 Envelope glycoprotein GP350 (Membrane antigen) (MA)
GP42_EBVB9 Glycoprotein 42 (gp42) [Cleaved into: Soluble gp42]
BZLF1_EBVB9 Lytic switch protein BZLF1 (EB1) (Protein Z) (Trans-activator protein BZLF1) (Zta) (bZIP ...
BILF1_EBVB9 G-protein coupled receptor BILF1 (GPCR BILF1)
EBNA1_EBVB9 Epstein-Barr nuclear antigen 1 (EBNA-1) (EBV nuclear antigen 1) (EC 3.1.21.-)
LMP1_EBVB9 Latent membrane protein 1 (LMP-1) (Protein p63) [Cleaved into: Protein p25]
GH_EBVB9 Envelope glycoprotein H (gH)
SCAF_EBVB9 Capsid scaffolding protein (Capsid protein P40) (Protease precursor) (pPR) (Protein EC-RF3/EC-RF3A) ...
EBNA2_EBVB9 Epstein-Barr nuclear antigen 2 (EBNA-2) (EBV nuclear antigen 2)
LMP2_EBVB9 Latent membrane protein 2 (Terminal protein)
KR2_EBVB9 Serine/threonine-protein kinase BGLF4 (EC 2.7.11.1)
ICP27_EBVB9 mRNA export factor ICP27 homolog (Mta) (ORF57 protein homolog) (Protein EB2) (Protein SM)
EBNA5_EBVB9 Epstein-Barr nuclear antigen leader protein (EBNA-LP) (EBV nuclear antigen leader protein) ...
IL10H_EBVB9 Viral interleukin-10 homolog (vIL-10) (20 kDa protein) (Protein BCRF1)
EAR_EBVB9 Apoptosis regulator BHRF1 (Early antigen protein R) (EA-R) (Nuclear antigen)
NEC2_EBVB9 Nuclear egress protein 2
BMRF2_EBVB9 Protein BMRF2
DUT_EBVB9 Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase)
DPOL_EBVB9 DNA polymerase catalytic subunit (EC 2.7.7.7)
EBNA6_EBVB9 Epstein-Barr nuclear antigen 6 (EBNA-6) (EBV nuclear antigen 6) (Epstein-Barr nuclear antigen 3C) ...
BRLF1_EBVB9 Replication and transcription activator (Rta) (Immediate-early protein Rta) (Protein R)
GL_EBVB9 Envelope glycoprotein L (gL)
GM_EBVB9 Envelope glycoprotein M (gM)
AN_EBVB9 Shutoff alkaline exonuclease (SOX) (EC 3.1.-.-)
BARF1_EBVB9 Secreted protein BARF1 (33 kDa early protein) (p33)
BNL2A_EBVB9 Protein BNLF2a
CEP3_EBVB9 Cytoplasmic envelopment protein 3
CEP2_EBVB9 Cytoplasmic envelopment protein 2 (Tegument protein BGLF2)
EBNA3_EBVB9 Epstein-Barr nuclear antigen 3 (EBNA-3) (EBV nuclear antigen 3) (Epstein-Barr nuclear antigen 3A) ...
KITH_EBVB9 Thymidine kinase (EC 2.7.1.21)
MTP_EBVB9 Major tegument protein (MTP) (Protein p140)
RIR1_EBVB9 Ribonucleoside-diphosphate reductase large subunit (R1) (EC 1.17.4.1) (Ribonucleotide reductase ...
GN_EBVB9 Envelope glycoprotein N
EBNA4_EBVB9 Epstein-Barr nuclear antigen 4 (EBNA-4) (EBV nuclear antigen 4) (Epstein-Barr nuclear antigen 3B) ...
PORTL_EBVB9 Portal protein
HELI_EBVB9 DNA replication helicase (EC 3.6.4.-)
TRM3_EBVB9 Tripartite terminase subunit 3 (EC 3.1.-.-) (Terminase large subunit)
UL95_EBVB9 Late gene expression regulator BGLF3
BDLF2_EBVB9 Protein BDLF2
DNBI_EBVB9 Major DNA-binding protein
LF2_EBVB9 Protein LF2
RIR2_EBVB9 Ribonucleoside-diphosphate reductase small subunit (EC 1.17.4.1) (Ribonucleotide reductase small ...
NEC1_EBVB9 Nuclear egress protein 1
TEG7_EBVB9 Tegument protein UL51 homolog
BALF1_EBVB9 Apoptosis regulator BALF1
TRM1_EBVB9 Tripartite terminase subunit 1
BKRF4_EBVB9 Tegument protein BKRF4
UL32_EBVB9 Packaging protein UL32 homolog
TRX1_EBVB9 Triplex capsid protein 1
ITP_EBVB9 Inner tegument protein
PRIM_EBVB9 DNA primase (EC 2.7.7.-)
BLRF2_EBVB9 Tegument protein BLRF2
BRRF1_EBVB9 Transcriptional activator BRRF1
BILF2_EBVB9 Glycoprotein BILF2
CVC1_EBVB9 Capsid vertex component 1
BDLF3_EBVB9 Glycoprotein BDLF3
MCP_EBVB9 Major capsid protein (MCP)
UL24_EBVB9 Protein UL24 homolog
CVC2_EBVB9 Capsid vertex component 2
UL92_EBVB9 Late gene expression regulator BDLF4
UNG_EBVB9 Uracil-DNA glycosylase (UDG) (EC 3.2.2.27) (UNG)
BFRF2_EBVB9 Late gene expression regulator BFRF2
SCP_EBVB9 Small capsomere-interacting protein
TRX2_EBVB9 Triplex capsid protein 2
UL87_EBVB9 Late gene expression regulator BcRF1 (TBP-like protein BcRF1)
CEP1_EBVB9 Cytoplasmic envelopment protein 1
HEPA_EBVB9 DNA helicase/primase complex-associated protein (HEPA) (Primase-associated factor)
BHLF1_EBVB9 Uncharacterized protein BHLF1
BLLF2_EBVB9 Uncharacterized protein BLLF2
BRRF2_EBVB9 Tegument protein BRRF2
LF3_EBVB9 Uncharacterized protein LF3
BTRF1_EBVB9 Uncharacterized protein BTRF1
BNL2B_EBVB9 Uncharacterized protein BNLF2b
LF1_EBVB9 Uncharacterized LF1 protein
RPMS1_EBVB9 Uncharacterized protein RPMS1

56 entries

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

Select_allDeselect_all
SCAF_EBVA8 Capsid scaffolding protein (Capsid protein P40) (Protease precursor) (pPR) (Protein EC-RF3/EC-RF3A) ...
GB_EBVA8 Envelope glycoprotein B (gB)
EBNA1_EBVA8 Epstein-Barr nuclear antigen 1 (EBNA-1) (EBV nuclear antigen 1) (EC 3.1.21.-)
LTP_EBVA8 Large tegument protein deneddylase (EC 3.4.19.12) (EC 3.4.22.-)
LMP2_EBVA8 Latent membrane protein 2 (Terminal protein)
BARF1_EBVA8 Secreted protein BARF1 (33 kDa early protein) (p33)
EAD_EBVA8 DNA polymerase processivity factor BMRF1 (Early Antigen Diffused) (EA-D) (Polymerase accessory ...
EAR_EBVA8 Apoptosis regulator BHRF1 (Early antigen protein R) (EA-R) (Nuclear antigen)
GN_EBVA8 Envelope glycoprotein N
IL10H_EBVA8 Viral interleukin-10 homolog (vIL-10) (20 kDa protein) (Protein BCRF1)
KR2_EBVA8 Serine/threonine-protein kinase BGLF4 (EC 2.7.11.1)
RIR1_EBVA8 Ribonucleoside-diphosphate reductase large subunit (R1) (EC 1.17.4.1) (Ribonucleotide reductase ...
BLRF2_EBVA8 Tegument protein BLRF2
TRM3_EBVA8 Tripartite terminase subunit 3 (EC 3.1.-.-) (Terminase large subunit)
RIR2_EBVA8 Ribonucleoside-diphosphate reductase small subunit (EC 1.17.4.1) (Ribonucleotide reductase small ...
CEP3_EBVA8 Cytoplasmic envelopment protein 3
CEP2_EBVA8 Cytoplasmic envelopment protein 2 (Tegument protein BGLF2)
GP350_EBVA8 Envelope glycoprotein GP350 (Membrane antigen) (MA)
LMP1_EBVA8 Latent membrane protein 1 (LMP-1) (Protein p63)
KITH_EBVA8 Thymidine kinase (EC 2.7.1.21)
GH_EBVA8 Envelope glycoprotein H (gH)
AN_EBVA8 Shutoff alkaline exonuclease (SOX) (EC 3.1.-.-)
GM_EBVA8 Envelope glycoprotein M (gM)
GL_EBVA8 Envelope glycoprotein L (gL)
BZLF1_EBVA8 Lytic switch protein BZLF1 (EB1) (Protein Z) (Trans-activator protein BZLF1) (Zebra) (Zta) (bZIP ...
ICP27_EBVA8 mRNA export factor ICP27 homolog (Mta) (ORF57 protein homolog) (Protein EB2) (Protein SM)
BMRF2_EBVA8 Protein BMRF2
MTP_EBVA8 Major tegument protein (MTP) (Protein p140)
CEP1_EBVA8 Cytoplasmic envelopment protein 1
MCP_EBVA8 Major capsid protein (MCP)
CVC2_EBVA8 Capsid vertex component 2
BKRF4_EBVA8 Tegument protein BKRF4
LF2_EBVA8 Protein LF2
BNL2A_EBVA8 Protein BNLF2a
BDLF2_EBVA8 Protein BDLF2
NEC1_EBVA8 Nuclear egress protein 1
TEG7_EBVA8 Tegument protein UL51 homolog
DUT_EBVA8 Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase)
DNBI_EBVA8 Major DNA-binding protein
DPOL_EBVA8 DNA polymerase catalytic subunit (EC 2.7.7.7)
PORTL_EBVA8 Portal protein
BRFL1_EBVA8 Replication and transcription activator (Rta) (Immediate-early protein Rta) (Protein R)
GP42_EBVA8 Glycoprotein 42 (gp42)
EBNA4_EBVA8 Epstein-Barr nuclear antigen 4 (EBNA-4) (EBV nuclear antigen 4) (Epstein-Barr nuclear antigen 3B) ...
ITP_EBVA8 Inner tegument protein
EBNA5_EBVA8 Epstein-Barr nuclear antigen leader protein (EBNA-LP) (EBV nuclear antigen leader protein) ...
EBNA2_EBVA8 Epstein-Barr nuclear antigen 2 (EBNA-2) (EBV nuclear antigen 2)
EBNA3_EBVA8 Epstein-Barr nuclear antigen 3 (EBNA-3) (EBV nuclear antigen 3) (Epstein-Barr nuclear antigen 3A) ...
EBNA6_EBVA8 Epstein-Barr nuclear antigen 6 (EBNA-6) (EBV nuclear antigen 6) (Epstein-Barr nuclear antigen 3C) ...
BRRF1_EBVA8 Transcriptional activator BRRF1
UL92_EBVA8 Late gene expression regulator BDLF4
BLLF2_EBVA8 Uncharacterized protein BLLF2
BNL2B_EBVA8 Uncharacterized protein BNLF2b
LF1_EBVA8 Uncharacterized LF1 protein
BTRF1_EBVA8 Uncharacterized protein BTRF1
BRRF2_EBVA8 Tegument protein BRRF2

1 entry

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

YEC4_EBVB9 Uncharacterized protein EC-RF4

56 entries

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

Select_allDeselect_all
LMP2_EBVG Latent membrane protein 2 (Terminal protein)
KR2_EBVG Serine/threonine-protein kinase BGLF4 (EC 2.7.11.1)
GB_EBVG Envelope glycoprotein B (gB)
SCAF_EBVG Capsid scaffolding protein (Capsid protein P40) (Protease precursor) (pPR) (Protein EC-RF3/EC-RF3A) ...
EBNA1_EBVG Epstein-Barr nuclear antigen 1 (EBNA-1) (EBV nuclear antigen 1) (EC 3.1.21.-)
BZLF1_EBVG Lytic switch protein BZLF1 (EB1) (Protein Z) (Trans-activator protein BZLF1) (Zebra) (Zta) (bZIP ...
ICP27_EBVG mRNA export factor ICP27 homolog (Mta) (ORF57 protein homolog) (Protein EB2) (Protein SM)
LTP_EBVG Large tegument protein deneddylase (EC 3.4.19.12) (EC 3.4.22.-)
GN_EBVG Envelope glycoprotein N
GP42_EBVG Glycoprotein 42 (gp42) [Cleaved into: Soluble gp42]
RIR2_EBVG Ribonucleoside-diphosphate reductase small subunit (EC 1.17.4.1) (Ribonucleotide reductase small ...
EAR_EBVG Apoptosis regulator BHRF1 (Early antigen protein R) (EA-R) (Nuclear antigen)
LMP1_EBVG Latent membrane protein 1 (LMP-1) (Protein p63)
IL10H_EBVG Viral interleukin-10 homolog (vIL-10) (20 kDa protein) (Protein BCRF1)
CEP2_EBVG Cytoplasmic envelopment protein 2 (Tegument protein BGLF2)
BARF1_EBVG Secreted protein BARF1 (33 kDa early protein) (p33)
KITH_EBVG Thymidine kinase (EC 2.7.1.21)
GH_EBVG Envelope glycoprotein H (gH)
TRM3_EBVG Tripartite terminase subunit 3 (EC 3.1.-.-) (Terminase large subunit)
AN_EBVG Shutoff alkaline exonuclease (SOX) (EC 3.1.-.-)
GM_EBVG Envelope glycoprotein M (gM)
GL_EBVG Envelope glycoprotein L (gL)
GP350_EBVG Envelope glycoprotein GP350 (Membrane antigen) (MA)
BMRF2_EBVG Protein BMRF2
EAD_EBVG DNA polymerase processivity factor BMRF1 (Early Antigen Diffused) (EA-D) (Polymerase accessory ...
RIR1_EBVG Ribonucleoside-diphosphate reductase large subunit (R1) (EC 1.17.4.1) (Ribonucleotide reductase ...
EBNA2_EBVG Epstein-Barr nuclear antigen 2 (EBNA-2) (EBV nuclear antigen 2)
MCP_EBVG Major capsid protein (MCP)
CVC2_EBVG Capsid vertex component 2
EBNA5_EBVG Epstein-Barr nuclear antigen leader protein (EBNA-LP) (EBV nuclear antigen leader protein) ...
BNL2A_EBVG Protein BNLF2a
TEG7_EBVG Tegument protein UL51 homolog
DNBI_EBVG Major DNA-binding protein
DPOL_EBVG DNA polymerase catalytic subunit (EC 2.7.7.7)
LF2_EBVG Protein LF2
BDLF2_EBVG Protein BDLF2
CEP1_EBVG Cytoplasmic envelopment protein 1
PORTL_EBVG Portal protein
BKRF4_EBVG Tegument protein BKRF4
BRLF1_EBVG Replication and transcription activator (Rta) (Immediate-early protein Rta) (Protein R)
EBNA6_EBVG Epstein-Barr nuclear antigen 6 (EBNA-6) (EBV nuclear antigen 6) (Epstein-Barr nuclear antigen 3C) ...
EBNA4_EBVG Epstein-Barr nuclear antigen 4 (EBNA-4) (EBV nuclear antigen 4) (Epstein-Barr nuclear antigen 3B) ...
EBNA3_EBVG Epstein-Barr nuclear antigen 3 (EBNA-3) (EBV nuclear antigen 3) (Epstein-Barr nuclear antigen 3A) ...
BLRF2_EBVG Tegument protein BLRF2
DUT_EBVG Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase)
ITP_EBVG Inner tegument protein
MTP_EBVG Major tegument protein (MTP) (Protein p140)
BRRF1_EBVG Transcriptional activator BRRF1
LF3_EBVG Uncharacterized protein LF3
BNL2B_EBVG Uncharacterized protein BNLF2b
BTRF1_EBVG Uncharacterized protein BTRF1
BALF1_EBVG Apoptosis regulator BALF1
RPMS1_EBVG Uncharacterized protein RPMS1
LF1_EBVG Uncharacterized LF1 protein
BRRF2_EBVG Tegument protein BRRF2
BLLF2_EBVG Uncharacterized protein BLLF2

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)