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Last update:
January 31, 2019
If you know
of other interactions, (or corrections) please
with Pubmed ID, host gene symbol/accession number and viral
interacting protein. Thank you and thanks to all who have sent reprints.
Please cite:- Susceptibility genes are enriched in those of the herpes
simplex (HSV-1) / host interactome in psychiatric and neurological
disorders. Pathogens
and disease 2013
NCBI
Books (free online edition)Human Herpesviruses Edited
by Ann Arvin, Gabriella Campadelli-Fiume, Edward Mocarski, Patrick
S. Moore, Bernard Roizman, Richard Whitley, and Koichi Yamanishi.
MANY OF THE PROTEINS
IN THIS NETWORK CAN BE FOUND IN ALZHEIMER'S DISEASE PLAQUES AND TANGLES
suggesting that these structures, which also contain immune and complement
related proteins, are cemeteries reflecting an immune battle between
host and virus Neurochem
Int 2010
Many risk factors implicated in Alzheimer's disease are able to reactivate
herpes simplex
ISRN Neurology, 2011 The Key genes
resulting from genome-wide association studies in Alzheimer's disease
can be related to herpes simplex and other pathogens' life cycles
and to the immune system Int.J.Alz.Dis
2011
Susceptibility genes are enriched in those of the herpes simplex
(HSV-1) / host interactome in psychiatric and neurological disorders.
Pathogens
and disease 2013
3-O-sulphated Heparan sulphate: Binds to glycoprotein D Shukla
et al,1999
Glycoprotein B binds to Heparan sulphate Oh
et al, 2010 heparan sulfate 2-O-sulfotransferase 1 HS2ST1
knockdown reduces viral entry O'Donnell
et al, 2010 HS3ST2 heparan sulfate (glucosamine) 3-O-sulfotransferase
2 HS3ST3A1 heparan sulfate (glucosamine) 3-O-sulfotransferase 3A1
HS3ST3B1 heparan sulfate (glucosamine) 3-O-sulfotransferase 3B1 and
HS3ST4 heparan sulfate (glucosamine) 3-O-sulfotransferase 4 and HS36ST5
heparan sulfate (glucosamine) 3-O-sulfotransferase 5 are the principal
isoforms modifying heparan sulphate for viral entry Xia
et al, 2002Tiwari
et al, 2006 Lawrence
et al, 2007
EXT1 (exostosin 1 or Glucuronosyl-N-acetylglucosaminyl-proteoglycan
4-alpha-N- acetylglucosaminyltransferase) mutation inhibits viral
entry by decreasing heparan sulphate synthesis Uyama
et al, 2006
OGT O-linked N-acetylglucosamine (GlcNAc) transferase:Inhibition
reduces replication of HSV-1 and Human Cytomegalovirus Angelova
et al, 2015.
Chondroitin 4,6-sulphate Binds to glycoprotein C Bergefall
et al, 2005 Soluble Chondroitin Sulphate types A, B, and
C strongly interfere with the adsorption of HSV-1 to the surface of
gro2C soluble chondroitin sulphate types A, B (dermatan sulphate)
, and C strongly interfere with the adsorption of HSV-1 to the surface
of gro2 Cells Banfield
et al, 1995 Chondroitin sulfate E provides the virus binding
sites on gro2C cells Bergefall
et al, 2005
CHST11carbohydrate (chondroitin 4) sulfotransferase 11: Enables
synthesis of the above: Overexpression incresases HSV-1 binding
to cells: Uyama
et al, 2006
The HSV-1 virion contains alpha 2,3 and alpha 2,6-linked sialic
acids which play a role in viral entry Teuton
and Brandt, 2007 (SIGLECS bind to sialic acid reidues:
SIGLEC1 and SIGLEC3 (CD33) bind to alpha 2,3- and alpha2,6-linked
sialic acids CD22 and SIGLEC6 to alpha 2,6 and MAG to alpha-2,3 linked
sialic acids Brinkman-Van
der Linden and Varki, 2000)
Phosphatidylcholine plays an important role in the binding of glycoproteins
B and H to lipid membranes in the fusion process Galdiero
et al, 2010
APOE
apolipoprotein E: APOE4 allele favours cerebral infection by HSV-1
Burgos
et al, 2003
Virus binds to all serum lipoprotein fractions VLDL
(Contains APOC2,
APOE) , LDL(contains
APOB. LPA),
HDL
(contains APOA1,
APOA2) the
virus binds to artificial proteoliposomes containing only one type
of apolipoprotein (A1 / E), possibly via glycoprotein B Huemer
et al, 1988
CADM3 cell adhesion molecule 3 (NECL1) brain-specific protein related
to the calcium-independent cell-cell adhesion molecules known as nectins
Akhtar
et al, 2008
ITGAX integrin, alpha X (complement component 3 receptor 4 subunit)
(CD11c): expression reduces the ability to reduce primary virus replication
in the eye Allen
et al, 2011
ITGB6 integrin, beta 6 : a5ß6- and a5ß8-Integrins are
Receptors for HSV gH/gL Gianni
et al, 2013
ITGB8 integrin, beta 8: a5ß6- and a5ß8-Integrins are
Receptors for HSV gH/gL Gianni
et al, 2013
MARCO macrophage receptor with collagenous structure; functions
together with heparan sulphate proteoglycans to mediate viral adsorption
to epithelial cells Macleod
et al, 2013
Gamma-secretase
(a complex of anterior pharynx defective 1 homolog APH1A, nicastrin
NCSTN, the presenilin enhancer PSENEN and presenilins PSEN1 or PSEN2)
cleaves a number of viral receptors including PVRL1, SDC1 and SDC2 ,
as well as APP (substrates
reviewed in Lleó and Saura, 2011).
F2R
coagulation factor II (thrombin) receptor: host-cell derived tissue
factor (TF) and virus-encoded glycoprotein C stimulate F2R enhanced
infection by triggering thrombin production Sutherland
et al, 2012
F2RL1
coagulation factor II (thrombin) receptor-like 1: Also involved in
the viral tissue factor related effects Sutherland
et al, 2012
F3
coagulation factor III (thromboplastin, tissue factor): Binds to the
virus Sutherland
et al, 1997
F7
coagulation factor VII (serum prothrombin conversion accelerator):
activated coagulation factors X (FXa) or VII (FVIIa) directly affect
HSV1 infection of human umbilical vein endothelial cells dependent
on viral TF and gC Sutherland
et al, 2012
F8
coagulation factor VIII, procoagulant component: Binds to viral
envelope Gershom
et al, 2010
CAV1 Caveolin : Cav1 co-localized with iNOS and HSV-1 in caveolae
in HSV-1 infected lung dendritic cells, suggesting their interaction.
Cav-1 deficiency led to an accelerated elimination of virus and less
lung pathological change following HSV-1 infection Wu
et al, 2015
MAP1LC3A microtubule-associated protein 1 light chain 3 alpha: HSV-1
induces a strong increase in GFP-LC3 and endogenous LC3 lipidation
Santana
et al, 2012
RHOT1 ras homolog family member T1 (miro-1) : Involved in the disruption
of mitochondrial transport by alpha herpes viruses via interaction
with kinesin-1 (KIF5B) Kramer
and Enquist, 2012
APP
Amyloid precursor protein: Involved in fast anterograde transport
of Herpes simplex ( squid axon); Major component of viral particles
Satpute-Krishnan
et al, 2003 also involved in transport in human epithelial
cells Cheng
et al, 2011 HSV-1 increases production of the APP intracellular
domain (AICD) and stimulates neprilysin (NEP) activity Civitelli
et al, 2015
Beta-amyloid (Aß 1-40 and Aß
1-42) inhibit HSV-1 replication Bourgade
et al, 2015
FLG filaggrin: IL-25 enhances herpes simplex virus (HSV-1) and vaccinia
virus replication by inhibiting filaggrin expression in skin biopsies
, but Filaggrin breakdown products inhibited HSV-1 replication in
vitro Kim
et al, 2013
RANBP10 RAN binding protein 10: ICP0 and RanBP10 promote viral gene
expression by regulating chromatin remodeling of the HSV-1 genome
for efficient viral replication Sato
et al, 2016.
Sphingomyelin and phosphatidylserine are incorporated into HSV-1
virions van
Genderen et al, 1994
Proteolytical digestion of albumin (ALB) , alpha-lactalbumin (LALBA)
, beta-lactoglobulin and lysozyme (LYZ) by trypsin, chymotrypsin and
pepsin produces peptide fragments with antiherpetic activity Oevermann
et al, 2003.
AMD1 adenosylmethionine decarboxylase 1: Inhibition prevents viral
infection Greco
et al, 2005 (Spermidine and spermine, are components of
the HSV-1 virion Gibson
and Roizman, 1971 : )
ASS1 argininosuccinate synthase 1: siRNA knockdown enhances viral
genome replication and the production of infectious virus Grady
et al, 2013
Arginine deprivation suppresses viral replication in tissue culture:
Lysine antagonized the viral growth-promoting action of arginine Griffith
et al, 1981
PFK1 phosphofructokinase, muscle : PFK1 knockdown impairs HSV-1
replication. and HSV-1 engagement of PFK1 increases glycolysis activation
and ATP production Abrantes
et al, 2012
CAT Catalase: The virus itself expresses
a catalase that may protect it from oxidative inactivation. (detoxifies
hydrogen peroxide by converting it to water and oxygen) Newcomb
and Brown, 2012
GSTP1 glutathione S-transferase pi 1: Protein regulated by infection
in hepatoma cells Santamaria
et al, 2009
NOX1 NADPH oxidase 1 Activated by infection in microglial cells
Hu
et al, 2011
SOD2 superoxide dismutase 2, mitochondrial: (MnSoD) Expression increased
in HSV-1 latent mouse trigeminal ganglion following heat stress Hill
et al,2001
CUL1 cullin 1: the large tegument protein dissociates NEDD8 from
CUL1 (also a property of the Epstein Barr protein BPLF1and the mouse
cytomegalovirus tegument protein) Gastaldello
et al, 2010
DCAF8 DDB1 and CUL4 associated factor 8 (wdr42a): binds to VP22
Li
et al, 2011
MORC3 MORC family CW-type zinc finger 3: an antiviral factor which
plays an important role during HSV-1 and HCMV infection.Sloan
et al, 2016
NEDD4 neural precursor cell expressed, developmentally down-regulated
4, E3 ubiquitin protein ligase : interacts with viral UL56 protein
Ushijima
et al, 2008
NEDD8 neural precursor cell expressed, developmentally down-regulated
8: the large tegument protein dissociates NEDD8 from CUL1 (also a
property of the Epstein Barr protein BPLF1and the mouse cytomegalovirus
tegument protein) Gastaldello
et al, 2010
PIAS2 protein inhibitor of activated STAT, 2: Components of promyelocytic
leukaemia (PML) nuclear bodies (ND10) (DAXX, SP100, SUMO1, SUMO2 SUMO3,
PIAS2) are recruited to sites associated with HSV-1 genomes soon after
nuclear entry Cuchet-Lourenço
et al, 2011 They act to repress infection Glass
and Everett, 2012
PIAS4 protein inhibitor of activated STAT 4: upregulated during
HSV-1 infection and localizes to nuclear domains that contain viral
DNA Conn
et al, 2016.
SMURF2 SMAD specific E3 ubiquitin protein
ligase 2: binds to VP22 Li
et al, 2011
SUMO1: SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae) recruited
to sites associated with HSV-1 genomes soon after nuclear entry Cuchet-Lourenço
et al, 2011
SUMO2: SMT3 suppressor of mif two 3 homolog 2 (S. cerevisiae) recruited
to sites associated with HSV-1 genomes soon after nuclear entry Cuchet-Lourenço
et al, 2011
SUMO3: SMT3 suppressor of mif two 3 homolog 3 (S. cerevisiae) recruited
to sites associated with HSV-1 genomes soon after nuclear entry Cuchet-Lourenço
et al, 2011
UBB ubiquitin B ICP4 specifically induces increased transcription
of the human ubiquitin B gene without affecting the ubiquitin A or
C genes.Kemp
and Latchman, 1983
CCND1
cyclin D1: Regulated by ICP0[78]
cyclin D1, D2, or D3 colocalize with ND10 bodies and ICP0 early in
infection and later become incorporated into viral replication compartments
Kalamvoki
and , Roizman ,2009
CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) HSV-1 Cgal(+)
increases quaking levels and with an increase of p27(Kip1) protein
levels in hepatoma cells Sánchez-Quiles
et al, 2011.
CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits
CDK4) inhibition of cdk4 by inhibitor I sequesters nuclear ICP0 Kalamvoki
and Roizman, 2009 (CDKN2B and CDKN2C also inhibit CDK4)
ATG7 autophagy related 7 homolog (S. cerevisiae): The antiviral
activity of Pentagalloylglucose is impaired in ATG7 knockout cells
Pei
et al, 2011
AXL receptor tyrosine kinase :An AXL/LRP1/RANBP9 complex mediates
dendritic cell efferocytosis and knockout of this complex enhanced
viral load, and decreased survival in HSV-1 infected mice Subramanian
et al, 2014.
BANF1 barrier to autointegration factor 1: associates with the HSV-1
genome during infection, Unphosphorylated BAF inhibits viral DNA replication
and gene expression Jamin
et al, 2014
BBC3 BCL2 binding component 3 (FLJ42994, JFY-1, JFY1, PUMA): contributes
to the death of antigen-specific T cells during shutdown of the immune
response to infection Fischer
et al, 2008.
BST2 – bone marrow stromal cell antigen 2 (tetherin): over-expression
inhibits HSV-1 release and HSV-1 depletes tetherin from infected cells
Zenner
et al, 2013.
C3
Glycoprotein C binds to complement C3b, iC3b and C3c but not to C3d
[85]Complement
system
C11orf30 (Emsy): The Akt1/EMSY/IFN-stimulated genes pathway is activated
by both viral infection and interferon , and inhibits the replication
of HSV-1 Ezell
et al, 2012
C19orf66 (RYDEN): Interferon stimulated gene that ihibits the replication
of the Dengue virus hepatitis C virus, Kunjin virus, Chikungunya virus,
HSV-1, and human adenovirus Suzuki
et al, 2016
CAMP cathelicidin antimicrobial peptide Antiviral (vs HSV-1) and
antibacterial peptide Gordon
et al, 2005
CCL2 chemokine (C-C motif) ligand 2 (MCP-1) : MCP-1 from HSV-1-infected
keratocytes attracts CD4(+) T cells into the cornea Lee
et al, 2008
CCL3 chemokine (C-C motif) ligand 3: (MIP-1-alpha, MIP1A, SCYA3
)protects mice from corneal infection Stuart
et al, 2008
CCL4 chemokine (C-C motif) ligand 4 ( ACT2, AT744.1, G-26, HC21,
LAG-1, LAG1, MGC104418, MGC126025, MGC126026, MIP-1-beta, MIP1B, MIP1B1,
SCYA2, SCYA4 )CCL3 CCl4 and CCL5 possess antiviral activity via binding
to glycoprotein B Nakayama
et al, 2006
CCL5 chemokine (C-C motif) ligand 5 (RANTES) : mediates leukocyte
adhesion and migration in HSV-1 encephalitis Teixeira
et al, 2010
CCL7 TNF-alpha, IL1B, IL6, IL12, CCL7, CCL8, CCL9, CXCL1, CXCL2,
CXCL4, and CXCL5. CXCL9 and CXCL10 are induced by herpes simplex infection
in microglial cells Aravalli
et al, 2009
CCL8 induced by herpes simplex infection in microglial cells Aravalli
et al, 2009
CCL9 induced by herpes simplex infection in microglial cells Aravalli
et al, 2009
CCL19 chemokine (C-C motif) ligand 19 (RP11-195F19.11-003, CKb11,
ELC, MGC34433, MIP-3b, MIP3B, SCYA19) CCL19 and CCL21 (CCR7 ligands)
enhance the protective immune response against the virus Toka
et al, 2003.
CCL20 chemokine (C-C motif) ligand 20 ( CKb4, LARC, MIP-3a, MIP3A,
SCYA20, ST38 ) upregulated by infection in corneal epithelial cells
and stromal keratocytes Shirane
et al, 2004
CCL21 chemokine (C-C motif) ligand 21 : CCL19 and CCL21enhance the
protective immune response against the virus (CCR7 ligands) Toka
et al, 2003.
CCR1, CCR2, CCR5, and CXCR3, (highly expressed on activated T cells,
macrophages and most immature dendritic cells), and the more broadly
expressed CCR7, were highly expressed and strongly induced in infected
cornea and trigeminal ganglia at 3 and 10 days postinfection Cook
et al, 2004
CCR3 Antibodies to CCR3 block interferon alpha induction by the
virus Ankel
et al, 1998 CCR3 and CCR6 are induced at sites of infection
during acute and latent phases Cook
et al, 2004
CCR5 chemokine (C-C motif) receptor 5 : attracts cell types that
reduce CNS damage but allow viral replication in the brain Teixeira
et al, 2010 See
Cook et al, 2004
CCR6 CCR6 and CCR3 are induced at sites of infection during acute
and latent phases Cook
et al, 2004
CCR7 chemokine (C-C motif) receptor 7 : Downregulated by infection
as a mechanism to escape immune attack Prechtel
et al, 2005
CD1D HMC class I antigen-like glycoprotein CD1D ;Downregulated by
infection via interaction with glycoprotein B, preventing recognition
by CD1d-restricted natural killer T cells apex
Rao
et al, 2011
CD8A : CD8a molecule (Leu2 T-lymphocyte antigen) Latency is reduced
in CD8 knockout mice Mott
et al, 2008
CD40LG CD40 ligand: CD40 activation exerts a direct inhibitory effect
on HSV-1, initiating from the very early stages of the infection by
exploiting PI3 kinase-dependent but autophagy-independent mechanisms
Vlahava
et al, 2014.
CD74 CD74 molecule, major histocompatibility complex, class II invariant
chain: General chaperone regulating antigen presentation for the immune
response Dixon
et al, 2005
CH25H cholesterol 25-hydroxylase: 25-hydroxycholesterol has antiviral
effects against various viruses (influenza, HSV-1, MCMV) Blanc
et al, 2013
CLU clusterin (sulphated glycoprotein 2): Induced by HSV-1 in BHK
cells Hope
et al, 1982
CRP
C-reactive protein, pentraxin-related: Generally involved in pathogen
defence and inflammatory responses:
CXCL1 induced by herpes simplex infection in microglial cells Aravalli
et al, 2009
CXCL2 chemokine (C-X-C motif) ligand 2: Recruits neutrophils to
sites of infection Wojtasiak
et al, 2010 induced by herpes simplex infection in microglial
cells Aravalli
et al, 2009
CXCL3 levels reduced by IL12 induced regression in herpes stromal
keratitis Frank
et al, 2010.
CXCL4 induced by herpes simplex infection in microglial cells Aravalli
et al, 2009
CXCL5 induced by herpes simplex infection in microglial cells Aravalli
et al, 2009
CXCL9 chemokine (C-X-C motif) ligand 9:Corneal T cell infiltration
in response to infection is reduced in knockout mice Wuest
et al, 2006 induced by herpes simplex infection in microglial
cells Aravalli
et al, 2009
CXCL12 Migration towards CXCL12 reduced in infected dendritic cells
Prechtel
et al, 2005
CXCL13 Gene expressions of chemokines acting on T cells and B cells,
(CCL19, CCL21, CXCL9, CXCL13, CXCL10, XCL1, and CXCL16) were up-regulated
and peaked at 3 days after infection in the cornea and trigeminal
ganglion Araki-Sasaki
et al, 2006
CXCR2 chemokine (C-X-C motif) receptor 2 (IL8 receptor) : Increases
viral virulence in relation to stromal keratitis
Banerjee et al, 2004
CXCR3 chemokine (C-X-C motif) receptor 3 (IP10 or MIG receptor)
: Modulates the effects of CXCL10 on infection Wuest
and Carr, 2008
CXCR4 chemokine (C-X-C motif) receptor 4: Downregulated by infection
as a mechanism to escape immune attack Prechtel
et al, 2005 Antibodies to CCXR4 block interferon alpha
induction by the virus Ankel
et al, 1998
Secreted glycoprotein G binds to human chemokines, including CCL18,
CCL22 CCL25, CCL26, CCL28, CXCL9, CXCL10, CXCL11, CXCL12a, CXCL12ß,
CXCL13 and CXCL14 Viejo-Borbolla
et al, 2012
FCGR1A FCGR1B Fc fragment of IgG, high affinity Ia and 1b receptor
(CD64) A herpes viral mimic of these receptors binds to immunoglobulin
G Lin
et al, 2004
FKBP4 FK506 binding protein 4, 59kDa: Protein regulated by infection
in hepatoma cells Santamaria
et al, 2009
FLT3LG fms-related tyrosine kinase 3 ligand: Latency is reduced
in CD8 knockout mice Mott
et al, 2008
HAVCR2 hepatitis A virus cellular receptor 2 (Tim-3) : regulates
viral immunopathology Sehrawat
et al, 2009
HLA-G The vurus blocks the intracellular transport of HLA-G in placentally
derived human cells Schust
et al, 1996.
IFI16 interferon, gamma-inducible protein 16: Immune sensor for
viral DNA Unterholzner
et al, 2010
IFIH1 interferon induced with helicase C domain 1: (MDA-5): Involved
in viral recognition in human macrophages Melchjorsen
et al, 2010 Interacts with US11 Xing
et al, 2012
IFNA1 interferon, alpha 1: establishes latency in sensory neorones
in vitro De
Regge et al, 2010
IFNAR1 interferon (alpha, beta and omega) receptor 1 (IFNA1 receptor)
IFNAR2 interferon (alpha, beta and omega) receptor 2
IL4 interleukin 4: Regulates the recruitment of leukocytes into
central nervous system following infection Vilela
et al, 2011. IL25 acts synergistically with IL4 and IL13
to enhance HSV-1 replication in vitro Kim
et al, 2013
IL6 interleukin
6 (interferon, beta 2): Binds to IL6
response elements in the LAT promoter and ICP0
genes [91]
induced by herpes simplex infection in microglial cells Aravalli
et al, 2009
IL7R interleukin 7 receptor: Knockour regulates infection and viral
encephalitis Lundberg
et al, 2008
IL8 interleukin 8: Expression of U(L)37 in transfected cells leads
to IkappaB degradation and activation of the IL8 gene Liu
et al, 2008
IL10 interleukin 10: Inhibits the production of imflammatory mediators
induced by infection Marques
et al, 2004
IL12A interleukin 12A (natural killer cell stimulatory factor 1,
cytotoxic lymphocyte maturation factor 1, p35) Regulates infection
in stromal keratitis Frank
et al, 2010 induced by herpes simplex infection in microglial
cells Aravalli
et al, 2009
IL12B interleukin 12B (natural killer cell stimulatory factor 2,
cytotoxic lymphocyte maturation factor 2, p40) Regulates infection
in stromal keratitis Frank
et al, 2010
IL13 interleukin 13: IL-4 and IL-13, modulate TLR9 and herpes simplex
virus-induced plasmacytoid dendritic cells Tel
et al, 2011 IL25 acts synergistically with IL4 and IL13
to enhance HSV-1 replication in vitro Kim
et al, 2013
IL17F interleukin 17F : Involved in the effects of IL6 on viral
inflammation Shim
et al, 2009
IL17RA interleukin 17 receptor A: knockout reduces stromal keratitis
in HSV-1 infection Suryawanshi
et al, 2011
IL18 interleukin
18: protects mice against viral infection [229]
IL21 interleukin 21: helps promote an immune response to vaccination
agsinst the virus Hu
et al, 2011
IL23A interleukin 23, alpha subunit p19 : knockout increases the
severity of infection Kim
et al, 2008
IL25 – interleukin 25: IL-25 acts synergistically with IL-4
and IL-13 to enhance HSV-1 replication in vitro Kim
et al, 2013
IL28A interleukin 28A (interferon, lambda 2): Suppresses infection
in human neuronal NT-2 cell line Zhou
et al, 2011
IL29 interleukin 29 (interferon, lambda 1): Mediates antiviral effects
in keratinocytes Zhang
et al, 2011
INSIG1 insulin induced gene 1: Mice more susceptible to infection
in INSIG1 knockout mice Wang
et al, 2014.
IRAK1 HSV-1-induced up-regulation of IL15 gene expression in monocytic
THP1 cells requires the presence of the adaptors MyD88, IRAK1, and
TRAF6 Ahmad
et al, 2008
IRF1 interferon regulatory factor 1: modulates the antiviral effects
of interferon alpha Kawamoto
et al, 2003
IFIT1 interferon-induced protein with tetratricopeptide repeats
1 (ISG56) IRF3 activation stimulates ISG56 expression in HSV-infected
cells Collins
et al, 2004
IFIT3 interferon induced protein with tetratricopeptide repeats
3 : viral UL41 diminishes the accumulation of IFIT3 mRNA to abrogate
its antiviral activity Jiang
et al, 2016.
KIAA0226 (Rubicon , SCAR15): Involved in the autophagy dependent
removal of microbial DNA Liang
et al, 2014
KLRK1 killer cell lectin-like receptor subfamily K, member 1: (NKG2D)
Involved in immune responses to HSV-1 reactivation Schepis
et al, 2009
LAT linker for activation of T cells: HSV-1 encoded Us3 protein
interrupts TCR signaling and interleukine2 production by LAT inactivation
Yang
et al, 2015
LCK
lymphocyte-specific protein tyrosine kinase Phosphorylated
by tegument VP11/12 Wagner
& Smiley, 2009
LGALS1 lectin, galactoside-binding, soluble, 1 : Expression and
secretion increased by infection leading to apoptosis of activated
T cells Gonzalez
et al, 2005
LGALS3 lectin, galactoside-binding, soluble, 3: HSV1 increases the
release and carbohydrate binding activity of galectin 3 King
et al, 2009 HSV1 binds to Galectin 3 Woodward
et al, 2013
LGALS9 lectin, galactoside-binding, soluble, 9: (Gelectin 9 : Ligand
for HAVCR2) regulates viral immunopathology Sehrawat
et al, 2009
LRP1 low density lipoprotein receptor-related protein 1: An AXL/LRP1/RANBP9
complex mediates dendritic cell efferocytosis and knockout of this
complex enhanced viral load, and decreased survival in HSV-1 infected
mice Subramanian
et al, 2014.
MAL2 T-cell differentiation protein 2 (gene/pseudogene) (MAL proteolipid
protein 2): Expression increased after infection, colocalising with
HSV-1 proteinsin a a human oligodendroglial cell line Bello-Morales
et al, 2005
MAVS mitochondrial antiviral signaling protein: Involved in viral
recognition in human macrophages Melchjorsen
et al, 2010
MB21D1 Mab-21 domain containing 1: (Cytosolic DNA sensor cyclic
GMP-AMP (cGAMP) synthase (cGAS)); Knockout mice more susceptible to
lethal infection with HSV-1 Li
et al, 2013
MICA MHC class I polypeptide-related sequence A: Involved in immune
responses to HSV-1 reactivation Schepis
et al, 2009
MIF
macrophage migration inhibitory factor (glycosylation-inhibiting factor)
(also dopachrome tautomerase) Virion component Loret
et al, 2008 and Stegen
et al, 2013
MON1B MON1 homolog B (yeast) (HSRG1) : HSV-1 stimulation-related
gene 1 protein): Inhibits viral replication by binding to cyclin T2
Wu
et al, 2011
MX1 myxovirus (influenza virus) resistance 1, interferon-inducible
protein p78 (mouse): Associates with HSV-1 virions and enhances infection
Ku
et al, 2011
MYD88 myeloid differentiation primary response gene (88): (signal
transducer in the interleukin-1 and Toll-like receptor signaling pathways)
ICP0 reduces myd88 and TIRAP levels Van
Lint et al, 2010
NLRC3 NLR family, CARD domain containing 3 : HSV-1-infected Nlrc3
knockout mice show enhanced innate immunity, reduced morbidity and
lower viral load Zhang
et al, 2014.
NLRP3 NLR family, pyrin domain containing 3: herpes virus infection
activates and causes redistribution of NLRP3 to nuclei (corneal epithelia)
Wang et al, 2015
PSMB5 proteasome (prosome, macropain) subunit, beta type, 5: binds
to tegument protein UL37 Kelly
et al, 2011
PSMB8 proteasome (prosome, macropain) subunit, beta type, 8 (large
multifunctional peptidase 7): Part of the immunoproteasome dowregulated
by infection suggesting a posible role in immune escape Eisemann
et al, 2009
PTGER2 prostaglandin E receptor 2 (subtype EP2), 53kDa: Downregulated
by infection via a mechanism involving the virion host shutoff protein
Theodoridis
et al, 2009
PTGER4 prostaglandin E receptor 4 (subtype EP4): Downregulated by
infection via a mechanism involving the virion host shutoff protein
Theodoridis
et al, 2009
PPIA
peptidylprolyl isomerase A (cyclophilin A) : Virion component
Loret
et al, 2008
PRH1 proline-rich protein HaeIII subfamily 1: Salivary proline rich
proteins and cystatins inhibit viral replication Gu
et al, 1995
PRH2 proline-rich protein HaeIII subfamily 2: Salivary proline rich
proteins and cystatins inhibit viral replication Gu
et al, 1995
RANBP9 RAN binding protein 9: An AXL/LRP1/RANBP9 complex mediates
dendritic cell efferocytosis and knockout of this complex enhanced
viral load, and decreased survival in HSV-1 infected mice Subramanian
et al, 2014.
RSAD2 radical S-adenosyl methionine domain containing 2 (viperin)
: UL41 counteracts viperin's antiviral activity by reducing its mRNA
accumulation Shen
et al, 2014
RXRA retinoid X receptor, alpha: attenuates the host antiviral response
for this and other viruses by suppressing type I interferon Ma
et al, 2015.
SAMHD1 SAM domain and HD domain 1: suppresses the replication of
a wide range of DNA viruses, including HSV-1, as well as retroviruses
Hollenbaugh
et al, 2013
SCAP SREBF chaperone: SCAP knockout mice are more susceptible to
HSV-1 infection Chen
et al, 2016
SLPI secretory leukocyte peptidase inhibitor: Downregulated by infection
Fakioglu
et al, 2008
TICAM1 toll-like receptor adaptor molecule 1: involved in innate
immunity against invading pathogens. via TLR3: mediates dsRNA induction
of interferon-beta (IFNB) via NFKB1 activation during an antiviral
immune response (RefSeq) ribonucleotide reductase R1 subunits of herpes
simplex virus 1 and 2 protect cells against poly(I · C)-induced
apoptosis by preventing TICAM1/RIPK1 interaction .Dufour
et al, 2011
TIRAP toll-interleukin 1 receptor (TIR) domain containing adaptor
protein: ICP0 reduces myd88 and TIRAP levels Van
Lint et al, 2010
TLR3
toll-like receptor 3 deficiency is an important determinant of
herpes simplex virus 1 encephalitis Guo
et al, 2011
TLR4 toll-like receptor 4: Expression induced by infection in astrocytes
Villalba
et al, 2012
TLR7 toll-like receptor 7: Virus-cell fusion stimulates a type I
interferon response with expression of interferon-stimulated genes,
in vivo recruitment of leukocytes and potentiation of signaling via
TLR7 and TLR9 Holm et al, 2012
TLR8 toll-like receptor 8: activation of TLR3 or TLR8 by poly-I:C
or single stranded RNA prior to HSV-1 infection reduces the susceptibility
of the neuronal cells to infection. Zhou
et al, 2009
TLR9 toll-like receptor 9 : Knockout increases susceptibility to
the virus Lima
et al, 2010
TMEM140 transmembrane protein 140: binds to and co-localize with
UL31 during viral infection Guan
et al, 2014
TMEM173 transmembrane protein 173: (ERIS; MITA; MPYS; NET23; STING;
FLJ38577): Knockout mice are more susceptible to infection Ishikawa
et al, 2009
TNF tumor necrosis factor : induced by herpes simplex infection
in microglial cells Aravalli
et al, 2009
TNFSF4 tumor necrosis factor (ligand) superfamily, member 4 (OX40L)
: Rapid infiltration of activated (OX40(+)) CD4(+) T cells into HSV-1-infected
corneas and expression of OX40L on MHC Class II-negative cells Lepisto
et al, 2007
TNFSF9 tumor necrosis factor (ligand) superfamily, member 9 (4-1BB
ligand) Deletion prevents herpetic stromal keratitis Seo
et al, 2003
TNFRSF1A tumor necrosis factor receptor superfamily, member 1A:
Regulates the severity of HSV-1 encephalitis Viela
et al, 2010
TNFRSF9 : tumor necrosis factor receptor superfamily, member 9 (4-1BB)
: Blockade prevents herpetic stromal keratitis Seo
et al, 2003
TRAF3 deficiency leads to impaired TLR3 resposes and increased susceptivility
to viral encephalitis Pérez
de Diego et al, 2010 Viral protein UL36 deubiquitinates
TRAF3 preventing recruitment of the downstream adaptor - tank binding
kinase TBK1 Wang
et al, 2013
TRAF6
TNF receptor-associated factor 6: Binds to tegument protein UL37[100]
TRD@ T cell receptor delta locus: TCR-gamma/delta cells limit HSV-1-induced
epithelial lesions and reduce mortality Sciammas
et al, 1997
TRG@ T cell receptor gamma locus: TCR-gamma/delta cells limit HSV-1-induced
epithelial lesions and reduce mortality Sciammas
et al, 1997
TRIM11 tripartite motif containing 11: negatively regulates interferon
beta and overexpression enhances viral infectivity and knockdown produces
the opposite effect Lee
et al, 2013
TRIM14 Trim14-/- mice are highly susceptible to lethal HSV-1 infection
Chen
et al, 2016
TYROBP TYRO protein tyrosine kinase binding protein: greater mortality
in female compared to male mice during systemic viral infections with
double-stranded DNA viruses (herpes simplex virus type I , murine
cytomegalovirus, and vaccinia virus ): This effect is reduced by inhibiting
TYROBP signalling Guers
et al, 2012
ULBP2 UL16 binding protein 2: Downregulated by infection Schepis
et al, 2009
CSNK2A2 casein kinase 2, alpha prime polypeptide:Knockdown results
in elevated interferon response in response to infection by DNA and
RNA viruses Du
et al, 2015.
GSK3B glycogen synthase kinase 3 beta : Phosphorylation stimulated
by US3 Chuluungaatar et al, 2010
HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog: Ras signalling
is involved in HSV-1 replication Farassati
et al, 2001 (HRASKRAS
and NRAS
bind to RAF1 and numerous other viral relevant proteins (links are
to NCBI interactions) NGF activates the latency transcript via ras
and raf signalling Frazier
et al, 2001
IKBKAP inhibitor of kappa light polypeptide gene enhancer in B-cells,
kinase complex-associated protein: binds to tegument protein UL37
Kelly
et al, 2011
IKBKE inhibitor of kappa light polypeptide gene enhancer in B-cells,
kinase epsilon: Part of the antiviral signalling network Liang
et al, 2011
IKBKG
inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase
gamma : ICP0 recruits USP7
which binds to and deubiquitinates IKKgamma Daubeuf
et al, 2009
IKBKE inhibitor of kappa light polypeptide gene enhancer in B-cells,
kinase epsilon: essential for regulating antiviral signaling pathways:
Jin
et al, 2011
JAK1 Janus kinase 1: JAK1 and STA2 rapidly disappear from infected
cells blocking the interferon pathway Chee
and Roizman, 2004
JUN jun proto-oncogene activated by infection leading to NFKB1 activation
Hargett
et al, 2006
KDR Kinase insert domain receptor (a type III receptor tyrosine
kinase) (VEGFR2): Inhibition reduces HSV-induced corneal angiogenesis
Sharma
et al, 2011
KRAS Ras signalling is involved in HSV-1 replication Farassati
et al, 2001 (HRASKRAS
and NRAS
bind to RAF1 and numerous other viral relevant proteins (links are
to NCBI interactions)
NGF nerve growth factor activates the latency transcript via ras
and raf signalling Frazier
et al, 2001
MAP2K1 mitogen-activated protein kinase kinase 1 (MEK1) : MEK, MAPK
and ERK signalling pathways are attenuated by HSV-1 in hepatoma cells
via activation of serine-threonine protein phosphatase 2A (PP2A) Santamaría
et al, 2009
MAP3K7 mitogen-activated protein kinase kinase kinase 7: (TAK1)
JNK activation by ICP0 blocked by TAK1 which binds to ICP0 Diao
et al, 2005
MAP3K12 mitogen-activated protein kinase kinase kinase 12: a neuronal
pathway involving MAPK8 activation is essential for initial HSV gene
expression during reactivation. MAPK8 activation is mediated by dual
leucine zipper kinase (DLK, MAP3K12) and MAPK8IP3 Cliffe
et al, 2015.
MAPK8IP3 mitogen-activated protein kinase 8 interacting protein
3 : a neuronal pathway involving MAPK8 activation is essential for
initial HSV gene expression during reactivation. MAPK8 activation
is mediated by dual leucine zipper kinase (DLK, MAP3K12) and MAPK8IP3
Cliffe
et al, 2015.
MAPK14 mitogen-activated protein kinase 14 (p38 MAP kinase): Activated
by ICP27 [101]
MTOR mechanistic target of rapamycin (serine/threonine kinase) :
activated by the us3 kinase Chuluunbaatar
et al, 2010
RPTOR regulatory associated protein of MTOR, complex 1: Silencing
triggers viral reactivation Kobayashi
et al, 2012
MYC v-myc myelocytomatosis viral oncogene homolog (avian): Expresssion
modified in infected monocytes Bruun
et al, 1998
NFKB1 nuclear factor of kappa polypeptide gene enhancer in B-cells
1 : activation is inhibited by the virion host shut off protein Cotter
et al, 2011
NFKBIB nuclear factor of kappa light polypeptide gene enhancer in
B-cells inhibitor, beta: Involved in viral replication Gregory
et al, 2004
NGF nerve
growth factor maintains latency in peripheral neurones [232]NGF
deprivation reactivates the virus in vitro[212]
NRAS neuroblastoma RAS viral (v-ras) oncogene homolog: Ras signalling
is involved in HSV-1 replication Farassati
et al, 2001 (HRASKRAS
and NRAS
bind to RAF1 and numerous other viral relevant proteins (links are
to NCBI interactions) NGF activates the latency transcript via ras
and raf signalling Frazier
et al, 2001
Phospholipase A2 (calcium-dependent unspecified form) copurifies
with the Herpes simplex Fc receptor Lehtinen
et al, 1988:
PLA2G4A phospholipase A2, group IVA (cytosolic, calcium-dependent):
is upregulated by infection in human brain cells Hill
et al, 2009
PIK3CA
phosphoinositide-3-kinase, catalytic, alpha polypeptide activated
directly by VP11/12 Wagner and Smiley, 2011
PIK3CG phosphoinositide-3-kinase, catalytic, gamma polypeptide:
Dominant negative mutant negatively affects viral entry and fusion
Tiwari
and Shukla, 2010
PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (p85):
recruited by HSV-1 tegument protein VP11/12 Strunk
et al, 2013
PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A
(Gadd34) : The gamma(1)34.5 protein, posseses a GADD34-related domain,
enabling it to bind to the cellular phosphatase PPP1CA (PP1alpha),Mulvey
et al, 2003 Expression upragulated by infection Cheng
et al, 2005
PPP2CA protein phosphatase 2, catalytic subunit, alpha isozyme:
Upregulated by infection in hepatoma cells Santamaria
et al, 2009
PPP2R1B protein phosphatase 2, regulatory subunit A, beta Upregulated
by infection in hepatoma cells Santamaria
et al, 2009
PRKAA1 protein kinase, AMP-activated, alpha 1 catalytic subunit
(part of AMPK) : HSV-1 modulates the AMPK/Sirt1 axis differentially
during the course of infection interfering with pro-apoptotic signaling
and regulating mitochondrial biogenesis Martin
et al, 2014.
PRKACA
protein kinase, cAMP-dependent, catalytic, alpha: Phosphorylated by
tegument kinase US3
( a PRKACA
mimic) [104]
PTK2 PTK2 protein tyrosine kinase 2: (Fak) Rapidly phosphorylated
after infection Cheshenko
et al, 2003
PTK2B PTK2B protein tyrosine kinase 2 beta (Fak2) Binds to VP22
Li et al, 2011
PTPN11 protein tyrosine phosphatase, non-receptor type 11: autophagy
negatively regulates reactive oxygen species -activated SHP2 (PTPN11)
, which, in turn, facilitates IFNG-induced STAT1 activation and cellular
inflammation in infected cells Chang
et al, 2010
RAC1 ras-related C3 botulinum toxin substrate 1 (rho family, small
GTP binding protein Rac1): Regulates infection: Petermann
et al, 2009
RAF1 v-raf-1 murine leukemia viral oncogene homolog 1 RAF and RAS
signalling are involved in the NGF mediated promotion of latency Frazier
et al, 1996 and A Ras/Raf kinase inhibitor reduced the
synthesis of HSV-1 in peripheral nerve sheath tumour cells Farassati
et al, 2008
RALGAPA1 Ral GTPase activating protein, alpha subunit 1 (catalytic):
binds to tegument protein UL37 Kelly
et al, 2011
RASA1 RAS p21 protein activator (GTPase activating protein) 1: RAF
and RAS signalling are involved in the NGF mediated promotion of latency
Frazier
et al, 1996 RASA1 and RASGRF1 are the Ras proteins involved
in NTRK1 signalling (NTRK1
interactions)
RAFGRF1 Ras protein-specific guanine nucleotide-releasing factor
1: RAF and RAS signalling are involved in the NGF mediated promotion
of latency Frazier
et al, 1996
RELA v-rel reticuloendotheliosis viral oncogene homolog A (avian):
(NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA,
or RELB ): Involved in viral replication Gregory
et al, 2004 RELA and NFKB1 bind to viral UL42 Zhang
et al, 2013
RIPK1 receptor (TNFRSF)-interacting serine-threonine kinase 1: binds
to ICP6 Huang
et al, 2015
RIPK3 receptor-interacting serine-threonine kinase 3: binds to ICP6
Wang
et al, 2014
SOCS1
suppressor of cytokine signaling 1: Virus binds to SOCS1
promoter [106]
SOCS3 suppressor of cytokine signaling 3: induced by infection ,suppressing
interferon signalling, required for efficient replication and lytic
infection of HSV-1Yokota
et al, 2005
SRC v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)
binds to ICP0 Liang
and Roizman, 2006
STAT1 signal transducer and activator of transcription 1: Modulates
host responses to the virus Pasieka
et al, 2009
STAT2 signal transducer and activator of transcription 2, 113kDa:
JAK1 and STA2 rapidly disappear from infected cells blocking the interferon
pathway Chee
and Roizman, 2004
VEGFA vascular endothelial growth factor A ICP4 binds to the VEGF
promoter Wuest
et al, 2011
YES1 v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1: binds to
ICP0 Liang
and Roizman, 2006
Cell
signalling
Mitochondrial
Mitochondria, and tegument proteins UL41
and UL46,
migrate to perinuclear regions, via microtubules, in infected cells
[107].
Large clusters of mitochondria group around the virus [108]
NUP358
Nucleoporin 358: (RanBP2) VP12 (tegument product of UL36)
enters nuclei via NUP214
and NUP35 [118]
NUPL2
nucleoporin like 2: Binds to capsid protein UL25[117]
SLC3A2 solute carrier family 3 (amino acid transporter heavy chain),
member 2: recruited with integrin ITGB1 to the nuclear membrane for
viral de-envelopment Hirohata
et al, 2015.
POLR2A polymerase (RNA) II (DNA directed) polypeptide A, 220kDa
Viral genes are transcribed by RNA polymarase II Lester
and DeLuca, 2011 HSV-1 causes Near-Complete Loss of RNA
Polymerase II Occupancy on the Host Cell Genome Abrisch
et al, 2015
POLR3A Polymerase (RNA) III (DNA directed) polypeptide A, 155kDa:
Detects viral DNA Chiu
et al, 2009
POLR3D Polymerase (RNA) III (DNA directed) polypeptide D, 44kDa
Chiu
et al, 2009
POLR3F Polymerase (RNA) III (DNA directed) polypeptide F, 39 kDa
Chiu
et al, 2009
RNASEL ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent)
: involved in the interferon beta-mediated suppression of viral replication
Carr
et al, 2003 ICP0 prevents RNase L-independent rRNA cleavage
in herpes simplex virus type 1-infected cells. Sobol
and Mossman, 2006
TAF1
TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated
factor, 250kDa Binds to tegument protein VP22[140]
TAF3 TAF3 RNA polymerase II, TATA box binding protein (TBP)-associated
factor, 140kDa: host epigenetic factor negatively regulating viral
gene expression in U2OS osteosarcoma cells Oh
et al, 2014
TAF9
TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated
factor, 32kDa Binds to tegument protein VP16[141]
TBP TATA box binding protein: ICP4 interacts with TBP, TFIIB, and
the TBP-associated factor 1 (TAF1) in vitro Lester
and DeLuca, 2011.
TIA1
TIA1 cytotoxic granule-associated RNA binding protein Binds to the
virion host shutoff (Vhs) tegument protein ( UL41)
Esclatine
et al, 2004
TIAL1 cytotoxic granule-associated RNA binding protein-like 1 :
HSV-1 induces cytoplasmic accumulation of TIA1/TIAL1 and the synthesis
and cytoplasmic accumulation of tristetraprolin (ZFP36) Esclatine
et al, 2004
THOC4
THO complex 4 (Aly/ref) Binds to ICP27 [133]
TOPBP1topoisomerase (DNA) II binding protein 1: RPA1 ATRIP, RPA1,
TopBP1, Claspin, and CINP (ATR pathway proteins) required for infection
Mohni
et al, 2013
TPT1 tumor protein, translationally-controlled 1: Protein regulated
by infection in hepatoma cells Santamaria
et al, 2009
TP53BP1 tumor protein p53 binding protein 1: recruited to viral
replication centres, together with BRCA1, POL2RA, and SP100 Lang
et al, 2015
TP63 tumor protein p63: Dysregulated by viral infection Orosz
et al, 2010
TP73 levels of the 44.5kDa p73 isoform increased in HSV-1-infected
HaCaT cells and primary keratinocytes.Megyeri
et al, 2009
TRIM27 tripartite motif containing 27: degraded by viral protease
ICP0 Conwell
et al, 2015
TSG101 tumor susceptibility gene 101: the HSV-1 large tegument protein,
VP1/2, interacts with and regulates the ubiquitination of Tsg101Caduco
et al, 2013
ZDHHC1 zinc finger, DHHC-type containing 1: positive regulator of
virus-triggered, MITA/STING-dependent immune signaling Zhou
et al, 2014
ZNF350 zinc finger protein 350: binds to tegument protein UL37 Kelly
et al, 2011
ZFP36
zinc finger protein 36, C3H type, homolog (mouse) (Tristetraprolin)
Binds to tegument protein UL41Esclatine
et al, 2004
ZMAT3 zinc finger, matrin-type 3 phosphorylated by US3 Erazo
et al, 2011
Human endogenous retrovirus W long terminal repeat (HERV-W LTR)
is activated by HSV-1 immediate early protein 1 Lee
et al, 2003
ARID3A AT rich interactive domain 3A
(BRIGHT-like) degraded by ICP0 Fukoyo
et al, 2011
ATRX alpha thalassemia/mental retardation syndrome X-linked: with
DAXX ,contributes to antiviral resistance to HSV-1 infection, an effect
counteracted by ICP0 Lukashchuk
and Everett, 2010
DAXX death-domain associated protein: with ATRX ,contributes to
antiviral resistance to HSV-1 infection, an effect counteracted by
ICP0 Lukashchuk
and Everett, 2010
ENDOG endonuclease G cleaves a sequence of the viral genome Huang
et al, 2002
EXOG – endo/exonuclease (5'-3'), endonuclease G-like : ENDOG
and EXOG involved in mitochondrial DNA depletion initiated by viral
UL12.5 Duguay
and Smiley, 2013
FANCI Fanconi anemia, complementation group I : the Fanconi anemia
genomic stability pathway is exploited by HSV-1 to promote viral DNA
synthesis and its productive growth Karttunen
et al, 2014
FANCD2 Fanconi anemia, complementation group D2: FANCI /FANCD2 interact
with a multisubunit complex containing the virus-encoded single-stranded
DNA-binding protein ICP8 Karttunen
et al, 2014
LIG3
ligase III, DNA, ATP-dependent Complexes with XRCC1
(see above)
NR3C1
glucocorticoid receptor binds to origin of replication site involved
in the enhancement of replication by dexamethasone
Hardwicke and Schaffer, 1997
KHSRP KH-type splicing regulatory protein: KSRP is required for
the decay of Ifna4 and Ifnb mRNAs by interaction with AU-rich elements:
increased IFN expression renders Ksrp knockout cells refractory to
HSV-1 and vesicular stomatitis virus infection Lin
et al, 2011
GABPA
GA binding protein transcription factor, alpha subunit 60kDa: Controls
the expression of viral intermediate genes via interaction with the
viral ICP4
promoter [156]
GABPB2
GA binding protein transcription factor, beta subunit 2" " [156]
HOXA5 homeobox A5: Increased severity of occular legions in HOXA5
transgenic mice Gaille
et al, 2005
METTL17 methyltransferase like 17: host epigenetic factor positively
regulating viral gene expression in U2OS osteosarcoma cells Oh
et al, 2014
NUMA1 nuclear mitotic apparatus protein 1: required for efficient
infection Yamauchi
et al, 2008
PDS5B PDS5, regulator of cohesion maintenance, homolog B: host epigenetic
factor negatively regulating viral gene expression in U2OS osteosarcoma
cells Oh
et al, 2014
PHF10 PHD finger protein 10: host epigenetic factor positively regulating
viral gene expression in U2OS osteosarcoma cells Oh
et al, 2014
PHF13 PHD finger protein 13 (SPOC1) downregulated by infection with
several viruses including HSV-1 (PHF13 mediates antiviral responses)
Schreiner
et al, 2013
PRMT1
protein arginine methyltransferase 1 : Methylates ICP27 Yu
et al, 2010
RCC1 regulator of chromosome condensation 1 Knockdown inhibits viral
replication Umene
and Nishimoto, 1996
ARL6IP4 ADP-ribosylation factor-like 6 interacting protein 4 : induced
by HSV-1 binding to cells and functions as a splicing inhibitor of
viral pre-mRNA Li
et al, 2002.
HSV-1 triggers the disruption of transcription termination of cellular,
but not viral, genes, resulting in extensive transcription for tens
of thousands of nucleotides beyond poly(A) sites and into downstream
genes, leading to novel intergenic splicing between exons of neighbouring
cellular genes. As a consequence, hundreds of cellular genes seem
to be transcriptionally induced but are not translated Rutkowski
et al, 2015.
DICER1 dicer 1, ribonuclease type III: HSV-1 expresses ~ 8 microrna's
with dicer elements and replicates more slowly in the absence of DICER1
Bogerd
et al, 2014
MIR23A microRNA 23a: Facilitates viral replication via suppression
of Interferon Regulatory Factor 1 Ru
et al, 2014.
MIR101-1 regulates HSV-1 replication by targeting ATP5B Zheng
et al, 2011
MIR132
microRNA 132: upregulated after infection negative affecting expression
of interferon-stimulated genes, facilitating viral replication (Kaposi's
sarcoma virus, cytomegalovirus and HSV-1) Lagos
et al, 2010.
MIR138 (MIR138-1 or MIR138-2 ?): a neuron-specific microRNA, miR-138,
represses expression of ICP0, a viral transactivator of lytic gene
expression Pan
et al, 2014.
MIR146A microRNA 146a: Upregulated by infection, resulting in complement
factor H ( CFH ) downregulation Hill
et al, 2009
MIR155 microRNA 155: knockout mice are susceptible to HSV-1 encephalitis
Bhela
et al, 2014
MIR320D1 microRNA 320d-1 : HSV-1 infection of BCBL-1 cells downregulates
miR-498 and miR-320d Yan
et al, 2013
MIR498 microRNA 498: HSV-1 infection of BCBL-1 cells downregulates
miR-498 and miR-320d Yan
et al, 2013
RARRES3 retinoic acid receptor responder (tazarotene induced) 3:
(aka RIG1) a small non-coding RNAs within the viral latency transcript
cooperates with the RNA sensor, retinoic acid inducible gene I (RIG-I),
to stimulate IFN-ß promoter activity and NFKB dependent transcription
in human or mouse cells da
Silva and Jones, 2013
BAX
BCL2-associated X protein: HSV-1 infection blocks BAX
translocation to mitochondria [193]
BCL2 B-cell CLL/lymphoma 2: ICP27 induces apoptotic cell death via
reactive oxygen species and BCL2 downregulation Kim
et al, 2008
BID
BH3 interacting domain death agonist Phosphorylated by tegument kinase
US3[194]
CAPN1 calpain 1, (mu/I) large subunit: ICP0 protein levels in cultured
primary neurones are increased by inhibition of calcium-activated
protease (calpain) activity or by calcineurin inhibition (PPP3CA,
PPP3CB PPP3CC) Chen
et al, 2000.
RIPK1
receptor (TNFRSF)-interacting serine-threonine kinase 1 binds to herpes
simplex ribonucleotide reductase R1 Dufour
et al, 2011
SH3GLB1 SH3-domain GRB2-like endophilin B1: Protein regulated by
infection in hepatoma cells Santamaria
et al, 2009
TGFB1
transforming growth factor, beta 1 Downregulated by a microRNA encoded
by the LAT transcript [201]
TGFBR2 transforming growth factor, beta receptor II (70/80kDa):Latency
is modified in TGFBR2 knockout mice Allen
et al, 2011
SIRT1 sirtuin 1: HSV-1 modulates the AMPK/Sirt1 axis differentially
during the course of infection interfering with pro-apoptotic signaling
and regulating mitochondrial biogenesis Martin
et al, 2014.
SIRT1 SIRT2 SIRT4 SIRT5 SIRT 6 exert broad antiviral activity HSV-1
included Koyuncu
et al, 2014
SMAD3
SMAD family member 3 Downregulated by a microRNA encoded by the LAT
transcript [201]
Adrenaline can reactivate the virus : Viral reactivation can be
blocked by propanolol (beta adrenergic receptor antagonist) Hill
et al, 1996Gebhardt
and Kaufman 1995 ADRB1or ADRB2
ADORA1 – adenosine A1 receptor: imiquimod (ADORA1 antagonist)
induces the host antiviral protein, cystatin A Kan
et al, 2012
DNA viruses stimulate the synthesis of cyclic guanosine monophosphate-adenosine
monophosphate ( cGAMP) which binds to STING, leading to the activation
of IRF3 and the induction of interferon-ß Wu
et al, 2013.
CALCA calcitonin-related polypeptide alpha: CGRP and substance P
increase pro-inflammatory cytokine production in HSV-1 infected macrophages
Yaraee
et al, 2003
Chloride channel inhibitors (tamoxifen and 5-nitro-2-(3-phenyl-propylamino)
benzoic acid ) suppress viral RNA synthesis, protein expression and
virus production Zheng
et al, 2014.
GRIN1 glutamate receptor, ionotropic, N-methyl D-aspartate 1: NMDA
receptor blockade reduces HSV-1-induced increases in class I expression
by brain-derived antigen presenting cells (CD45(hi), suggesting that
blockade of the NMDA receptor may limit CNS inflammation. Nair
et al, 2007
Expression increased in the trigeminal ganglia of infected mice
treated with immunosuppressants (cyclophosphamide and dexamethasone)
cyclin CCND2, ERBB2, GNAS, plasma glutathione peroxidase GPX3, glutathione
transferase GSTM2, methyl CpG-binding protein 2 MECP2, pancreatic
and duodenal homeobox 1 PDX1, peripherin (PRPH) prostaglandin E2 receptor
PTGER4,retinal S-antigen SAG, Higaki
et al, 2002
Expression decreased in the trigeminal ganglia of infected mice
treated with immunosuppressants (cyclophosphamide and dexamethasone)
peripheral myelin protein 22 (PMP22), decorin DCN , transcription
factor AP-1 (JUN) , dystroglycan DAG1 , myelin protein zero MPZ ,
mitogen-activated protein kinase 3 (MAP3K3), prothymosin beta 4 TMSB4X,
and brain lipid-binding protein (FABP7 )
Higaki et al, 2002
MTMR4 myotubularin related protein 4: (human homolog of the rhesus
gene (LOC714621) used in the study) ownregulation of phosphatase genes
(PNKP, SNAP23, PTPRU, LOC714621 and PPM1M) inhibits HSV-1 infection
in rhesus astrocytes Yue
et al, 2013
PNKP – polynucleotide kinase 3'-phosphatase: downregulation
of phosphatase genes (PNKP, SNAP23, PTPRU, LOC714621 and PPM1M) inhibits
HSV-1 infection in rhesus astrocytes Yue
et al, 2013
PPM1M – protein phosphatase, Mg2+/Mn2+ dependent, 1M: downregulation
inhibits HSV-1 infection in rhesus astrocytes Yue
et al, 2013
PTPRU – protein tyrosine phosphatase, receptor type, U: downregulation
inhibits HSV-1 infection in rhesus astrocytes Yue
et al, 2013
QKI QKI, KH domain containing, RNA binding (Quaking) : QKI deletion
of viral reduces immediate-early protein levels and viral yield Sánchez-Quiles
et al, 2011
ROBO4 roundabout homolog 4, magic roundabout (Drosophila): activation
reduces the sverity of viral keratitis Mulik
et al, 2011
SCG2 secretogranin II: Herpesviruses may target this protein to
facilitate enhanced virus release from the host.: Berard
et al, 2015
SNAP23 synaptosomal-associated protein, 23kDa: downregulation of
phosphatase genes (PNKP, SNAP23, PTPRU, LOC714621 and PPM1M) inhibits
HSV-1 infection in rhesus astrocytes Yue
et al, 2013
Sodium channels in the dorsal root ganglia are internalised by HSV-1
infection (subtype not characterised) Storey
et al, 2002
TAC1 tachykinin, precursor 1: encodes four products of the tachykinin
peptide hormone family, substance P and neurokinin A, neuropeptide
K and neuropeptide gamma: substance P enhances the cytopathic effect
of HSV in macrophages Yaraee
et al, 2007
TH tyrosine hydroxylase activity depressed immediately after infection
in PC12 cells Rubenstein
et al, 1985
Viral replication in neurones is regulated by neuronal activity,
increased by GABA and Tetrodotoxin
(voltage dependent sodium channel blocker ) and reduced by potassium
chloride and GABA A receptor blockade (Subtype unknown : most GABA
receptors contain GABRA1) Zhang
et al, 2005
Nicotine patches reactivate the virus in latently infected rabbits
Myles
et al, 2003 an effect blocked by bupropion
( a dopamine/noradrenaline uptake blocker) Myles
et al, 2004
A vacuolar H(+)-ATPase plays a role in the interferon mediated inhibition
of viral glycoprotein transport Sidhu
et al, 1999 Precise gene not identified but could be any
of these
candidates Concanamycins A (Conmy A) and B (Conmy B), which
inhibit these atpases, block viral replication Hayashi
et al, 2001
Host Gene Methylation
DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha: nuclear association
between viral capsid proteins and DNMT3A Rowles
et al, 2015
KDM1A
lysine (K)-specific demethylase 1A (histone demethylase) Recruited
to viral intermediate early promoters, an effect inhibited by monoamine
oxidase inhibitors [183]
KDM4E lysine (K)-specific demethylase 4E : Inhibition has anti-viral
activity against both HSV-1 and human cytomegalovirus infection via
inhibition of viral intermediate early gene expression Rai
et al, 2013
ICAM5 intercellular adhesion molecule 5, telencephalin: Regulates
cerebral chemokine and cytokine production in the brains of infected
mice Tse
et al, 2009
IL6
interleukin 6 (interferon, beta 2) : can reactivate the virus [91]
Dehydroepiandrosterone, epiandrosterone and synthetic analogues,
possess antiviral activity Torres
et al, 2012
PTGS2:
Cyclo-oxygenase 2 inhibition (bromfenac) can inhibit viral reactivation
as can aspirin (and ibuprofen in vitro) [222][223][224]
Indomethacin suppresses viral replication [225]
LALBA lactalbumin, alpha-: Esterified lactalbumin has antiviral
activity Sitohy
et al, 2007
Lysine has been reported to be of benefit in human infections [231]
(no clinical trial yet to support this)
IDO1 (indoleamine 2,3-dioxygenase 1) (activated by IFNG) and TDO2
(tryptophan 2,3-dioxygenase activation have general antiviral and
antibacterial effects which are blocked by tryptophan Adams
et al, 2004Schmidt
et al, 2009 Spinal quinolinic acid levels and kynurenine
hydroxylase activity ( KMO) are raised by infection Reinhard,
1998
SLC1A2 solute carrier family 1 (glial high affinity glutamate transporter),
member 2: Microglial SLC1A2 is upregulated by infection to provide
glutathione and glutathione synthase (GSS) inhibition increases infection
Persson et al, 2007
Vitamin E defficiency but not supplementation affects viral pathogenicity
[241]
Adequete Vitamin E levels are important for trafficking antigen-specific
T cells to the brain, and dietary Vitamin E levels modulate T regulatory
and dendritic cells in the periphery Sheridan
and Beck, 2009.
TNFR1
(TNFRSF1A tumor necrosis factor receptor superfamily, member 1A )
knockout increases viral replication and lethality [242]
Mannose-6-phosphate is part of a pathway responding to viral stress
by depleting host lipid-linked oligosaccharides required for N-glycosylation
of viral-associated polypeptides Gao
et al, 2011.
Neem
extracts have antiviral activity in vitro
[247]
AQP1 aquaporin 1 (Colton blood group): and AQP4 aquaporin 4: In
murine herpes simplex encephalitis AQP4 is downregulated in the acute
phase of disease and AQP4 and AQP1 upregulated in the long term. These
transporters regulate cerebral oedema Martinez
Torres et al, 2007
BACE1 beta-site APP-cleaving enzyme 1: Expression increased in infected
cells, along with that of nicastrin Wozniak
et al, 2007 BACE1 is activated by HSV-1 via the viral activated
kinase pkt (EIF2AK2) resulting in beta-amyloid accumulation Ill-Raga
et al, 2011
c12orf10 chromosome 12 open reading frame 10 (MYG1) Protein regulated
by infection in hepatoma cells Santamaria
et al, 2009
CAPN3 calpain 3, (p94): Calpain and calcineurin inhibitors increase
the amount of the ICP0 viral protein in infected primary neurones
and PC12 cells in culture Chen
et al, 2000 CAPN3 is present in PC12 cells Marcilhac
et al, 2006 (and probably others): Numerous calcineurin
regulatory subunits exist including PPP3CA PPP3CB PPP3CC PPP3R1 and
PPP3R2
CCT3 chaperonin containing TCP1, subunit 3 (gamma): binds to tegument
protein UL37. Kelly
et al, 2011
NARS2 asparaginyl-tRNA synthetase 2, mitochondrial (putative) :binds
to tegument protein UL37. Kelly
et al, 2011
Viral Glycoprotein I posesses a mucin domain that is a universal
substrate for O-Glycosylation by several transferases including GALNT1
UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase
1 (GalNAc-T1):; GALNT2 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide
N-acetylgalactosaminyltransferase 2 (GalNAc-T2)): GALNT4 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide
N-acetylgalactosaminyltransferase 4 (GalNAc-T4)) and GALNT11 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide
N-acetylgalactosaminyltransferase 11 (GalNAc-T11) ) Norberg
et al, 2007
HSV-1 viral immediate early RNA interacts with host factors, resulting
in transcription of three dormant host fucosyltransferase genes (FUT3,
FUT5, and FUT6), whose gene products are rate-limiting for the synthesis
of a selectin receptor, the carbohydrate epitope sialyl Lewis X (sLe(x))
Nordén
et al, 2009 FUT7 also upregulated by infection in T cells
Nordén
et al, 2013
Iron : ICP8 possesses a divalent cation binding site necessary for
function : Bryant
et al, 2012
KLHL24 kelch-like family member 24: hsv1-mir-H27, encoded within
the viral genome, targets the mRNA of the cellular transcriptional
repressor KLHL24 which inhibits transcriptional efficiency of viral
immediate-early and early genes Wu
et al, 2013.
MSR1 macrophage scavenger receptor 1: knockout mice show increased
susceptibility to infection with Listeria monocytogenes or herpes
simplex virus type-1 Suzuki
et al, 1997
OLR1 oxidized low density lipoprotein (lectin-like) receptor 1:
Promoter activity and expression increased by HSV-1 in endothelial
cells Chirathaworn
et al, 2004
SEMG1 SEMG2: Semenogelins, semen-derived enhancer of viral infection
(ACPP) and seminal plasma enhance both HSV-1 and -2 infections in
cell culture Torres
et al 2015.
EBNA-1
(Epstein-Barr Viral protein ) can transactivate immediate-early HSV-1
expression.Machuca
et al, 1990
UNC93B1 unc-93 homolog B1 (C. elegans) : Absence
of UNC93B1 leads to a survival disadvantage but does not impact viral
replication or type I interferon levels in the brain in HSV-1-infected
mice Wang
et al, 2011
Bulk experiments
Time-resolved Global and Chromatin Proteomics during Herpes Simplex
Virus Type 1 (HSV-1) Infection.Mol Cell Proteomics Kulej
et al, 2017 See supplementary table S1 in this paper for
a list of s> 4000 proteins modified by infection
Proteomic analysis of cells in the early stages of herpes simplex
virus type-1 infection reveals widespread changes in the host cell proteome.Antrobus
et al, 2009
HSV-1 Cgal+ infection promotes quaking RNA binding protein
production and induces nuclear-cytoplasmic shuttling of quaking I-5
isoform in human hepatoma cells.SantaMaria
et al, 2009
Binding of Herpes Simplex Virus Type-1 Virions Leads to the
Induction of Intracellular Signalling in the Absence of Virus Entry
: MacLeod
and Minson, 2010
A Systematic Analysis of Host Factors Reveals a Med23-Interferon-gamma
Regulatory Axis against Herpes Simplex Virus Type 1 ReplicationGriffiths
et al, 2013 (in progress).
Proteomic analysis of the herpes simplex Virus 1 virion protein
16 transactivator protein in infected cells Oh
and Knipe 2015