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Herpes simplex (HSV-1) interacts with a number of host transcription factors, certain of which are depicted in this table.  When binding to the virus, their interaction with human genes is obviously impaired. These transcription factors control the expressionof many of the genes implicated in Alzheimer’s disease, as shown.  Genes reportedly associated with Alzheimer’s disease are in bold type.

This supplementary table relates to the publication:- "Interactions between the products of the Herpes simplex genome and Alzheimer's disease susceptibility genes: Relevance to pathological signalling cascades" Neurochem.Int 52, 920-934, 2008

Host Transcription Factor

Viral interactions

Alzheimer’s disease susceptibility candidates controlled by transcription factor



GABPA (one of several genes known as nuclear respiratory factor 2) and GABPB2 control the expression of Herpes viral intermediate genes via an interaction with the viral ICP4 promoter 25.

PSEN193 and mitochondrial respiratory genes via the control of the mitochondrial transcription factor TFAM 120.


The ICP0 protein of HSV1 interacts with certain histone deacetylases (HDAC4, 5 and 9) via an amino terminal domain responsible for suppressing the activity of myocyte enhance factor MEF2A by nuclear sequestration.  ICP0 overcomes the HDAC mediated suppression of MEF2A 76

BACE1 69.


VP16 associates with host cell factor-1 (HCF1) and the transcription factor oct-1 (POU2F1) forming a complex responsible for the transcription of viral immediate early genes 77,125.

BACE2 79, BCHE 53, CCR2 126, (CRP) 121, LPL 97OLR1 9, TNF 47.


HSV-1 infection results in an early activation of the transcription factor nuclear factor kappa beta (NFKB1) an effect mediated via the viral proteins ICP4 and ICP2743. 

A2M2, ABCA1 11,APOE 26, APP 37, AR 108, BACE1100, CCL2 116,CRP 121,133, CYP19AS1 28, FAS 5, GSK3B 22, ICAM1 8, IL1B 46, IL1RN 33. IL6 80, MMP1, MMP3 3NOS3 18, OLR110, PLAU 42, PTGS2 105, TGFB1 73, TNF 56.  NFKB also downregulates the transcriptional activity of the AICD/APBB1 activator.  AICD is a gamma-secretase cleaved product of APP133.


Herpes simplex infection increases SP1 phosphorylation, an effect involving ICP4 and ICP27SP1 phosphorylation reduces its transcriptional efficacy63.

ABCA1 106, ABCA2 19, ACE 27, ADRB1 89, ALDH2 110, APOA141, APOC3 61, APOE 6, APP 95, APBB1 49, AR 112, ARSA 65, BACE1 15, BACE2 79, C4A 118, CCL2 67,CDC2 115, CETP 111CHAT 52,CHRNA3 31, COL11A1 131, CYP19A1 134, CST3 86, CTSD 98, DLD 29, DLST 85,ESR1 20, FGF194, HFE 83, HSPG2 16, ICAM1 130, IL1A 81, IL1B 50, IL6 102,LDLR1, LPL 128, MAOA 90, MAPT 44, MME 107, MPO 59, MTHFR 48,MTRR 72,NOS1 104, NOS3 60, OPRS1 96, TF 74, PARP1 132, PLAT 32, PLAU 51, PON1 4, POU2F1 39, PNMT 109, PPARA 13, PRNP 78, PSEN1 92PSEN2 99, PTGS2 117, RUNX1 36, SERPINE1 12, SLC6A4 45, SOAT1 127, TFAM 114,TGFB1 64, TNF 103, TP73 24, VEGFA 113


Binds to the LAT promoter 66

APOE 68, BACE1 14, CCL2 119, FAS 57,  FCERG1 30,  ICAM1 7, SOAT1 127.


The herpes simplex genome contains three origins of replication sites, one of which contains concensus binding sites for the transcription factors NF-1 and CP2 (TFCP2)17

ESR1 70GSK3B 71.



The LAT promoter binds to the host USF transcription factor family 62

ABCA1129, APOC3 91APOE 101APP 122, CDC2 87CTSD  123, CYP19A1 54, ESR1 21, PAI1 23 and TGFB1 124.


A number of viral genes (ICP0, US5, UL19, UL27, UL37, UL48) bind to the host transcription factor yin-yang-1 (YY1) which controls their expression 38,75,82

BACE169, FAS34,  IL440, NOS3 60PARP1 88,  PTGS2 55 SREBF1 1,84 and TFCP258. YY1 also controls the expression of many cholesterol and lipoprotein-related genes via an interaction with sterol regulatory binding protein sites (SREBF1).  YY1 binds to Srebp1a and disrupts its binding to the sterol-response element.  Via this interaction it represses the SRE-mediated expression of the lipoprotein receptor LDLR as well as that of the steroidogenic acute regulatory protein (StAR) 1,84.  Conversely YY1 positively controls the expression of the cholesteryl ester transfer protein (CETP) 35.

REST A Repressor Element-1/Neuronal Restrictive Silencer Element (RE-1/NRSE) is located between HSV-1 genes ICP22 and ICP4.Pinnoji et al, 2007 In progress





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