Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0005373
UniProt IDQ14653
Primary gene name(s)IRF3
Synonym gene name(s)unknown
Protein nameInterferon regulatory factor 3
Protein functionKey transcriptional regulator of type I interferon, IFN-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes, IFN-alpha and IFN-beta and IFN-stimulated genes, ISG by binding to an interferon-stimulated response element, ISRE in their promoters. Acts as a more potent activator of the IFN-beta, IFNB gene than the IFN-alpha, IFNA gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA, dsRNA, or toll-like receptor, TLR signaling, is phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein, CREBBP to form dsRNA-activated factor 1, DRAF1, a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages.
Subcellular locationCytoplasm {ECO:0000269|PubMed:10805757}. Nucleus {ECO:0000269|PubMed:10805757}. Note=Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect. When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q14653
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to dsRNA [GO:0071359];
defense response to virus [GO:0051607];
interferon-gamma-mediated signaling pathway [GO:0060333];
lipopolysaccharide-mediated signaling pathway [GO:0031663];
macrophage apoptotic process [GO:0071888];
MDA-5 signaling pathway [GO:0039530];
negative regulation of type I interferon production [GO:0032480];
positive regulation of cytokine secretion [GO:0050715];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of interferon-alpha production [GO:0032727];
positive regulation of interferon-beta production [GO:0032728];
positive regulation of type I interferon-mediated signaling pathway [GO:0060340];
positive regulation of type I interferon production [GO:0032481];
programmed necrotic cell death [GO:0097300];
response to exogenous dsRNA [GO:0043330];
transcription from RNA polymerase II promoter [GO:0006366];
TRIF-dependent toll-like receptor signaling pathway [GO:0035666];
type I interferon biosynthetic process [GO:0045351];
type I interferon signaling pathway [GO:0060337]
Gene Ontology
(Molecular Function)
Complete annatation
DNA binding [GO:0003677];
identical protein binding [GO:0042802];
protein homodimerization activity [GO:0042803];
RNA polymerase II core promoter proximal region sequence-specific DNA binding [GO:0000978];
transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001078];
transcription cofactor activity [GO:0003712]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction109869
Phylogenetic treeQ14653
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-0.7283726287932110.02736046406366180.0602758958803862
AZA vs. DISU0.2525856451866360.3182636328199870.870080690516335
AZA vs. IL7-0.2205187123897840.3160610188501290.999311006273513
AZA vs. SAHA0.3456596629313830.1578728859413310.505904736964206
DISU vs. CD30.967714399085440.008222976352835860.0246427724736874
DISU vs. IL7-0.4827934107583850.05583163761163450.310576360514904
DISU vs. SAHA0.09635636053958090.7414969912869870.92537457843182
DMSO vs. AZA0.06321663682434380.7064959784261931
DMSO vs. CD30.778804379779030.01576210040262540.0366049086735858
DMSO vs. DISU-0.1913571888453340.4329262334613850.881718877024027
DMSO vs. IL7-0.2762385068840010.1253995023368620.620616381394679
DMSO vs. SAHA0.2780318694953740.2395488557932410.587508674639533
HIV vs. Mock in Activation0.1189889842952530.8492464577347990.999983755607037
HIV vs. Mock in Latency0.09057542775762610.5837646503793860.999834320637052
IL7 vs. CD30.5126443866187780.1122217746730980.207245663904078
SAHA vs. CD31.051095398263350.003550054568749570.0106086302500607
SAHA vs. IL70.563968431761470.0213620089858930.104748543065871
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.0531608 0.81326
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.146 1.024 1.118 1.172 1.186
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1J2F X-ray 2.3Å A/B=175-427.
1QWT X-ray 2.1Å A/B=173-427.
1T2K X-ray 3.0Å A/B=1-112.
1ZOQ X-ray 2.3Å A/B=196-386.
2O61 X-ray 2.8Å A=9-111.
2O6G X-ray 3.1Å E/F/G/H=1-123.
2PI0 X-ray 2.3Å A/B/C/D=1-113.
3A77 X-ray 1.8Å A/B/C/D=189-427.
3QU6 X-ray 2.3Å A/B/C=1-113.
5JEJ X-ray 2.0Å A/B=189-427.
5JEK X-ray 2.4Å A/B=189-427.
5JEL X-ray 1.6Å A=189-427.
5JEM X-ray 2.5Å A/B/E/G=189-398.
5JEO X-ray 1.7Å A=189-427.
5JER X-ray 2.9Å A/C/E/G=189-427.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Vpu co-localizes with 22593165
Vpu interacts with 22647704
Vpr degrades 18082865
Vpu complexes with 22593165
Vpu induces cleavage of 25352594
Vif induces cleavage of 25352594
capsid interacts with 24196705
Tat induces phosphorylation of 22709905
Vpr inhibits 21411754
reverse transcriptase activates 23929945
Vpr induces cleavage of 25352594
Nef activates 17182689
Vif degrades 18082865

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa04623 Cytosolic DNA-sensing pathway - Homo sapiens (human)
hsa05133 Pertussis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)