Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000789
UniProt IDO95786
Primary gene name(s)DDX58
Synonym gene name(s)unknown
Protein nameProbable ATP-dependent RNA helicase DDX58
Protein functionInnate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA, <1 kb in length. In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Upon ligand binding it associates with mitochondria antiviral signaling protein, MAVS/IPS1 which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons, IFNs; IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus, MeV, Rhabdoviridae: vesicular stomatitis virus, VSV, Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus, JEV, hepatitis C virus, HCV, dengue virus, DENV and west Nile virus, WNV. It also detects rotavirus and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus, EBV. Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs, EBERs. May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. {ECO:0000269|PubMed:15208624, ECO:0000269|PubMed:15708988, ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19122199, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19576794, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:21742966}.
Subcellular locationCytoplasm. Cell projection, ruffle membrane. Cytoplasm, cytoskeleton. Cell junction, tight junction. Note=Colocalized with TRIM25 at cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton at membrane ruffles.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O95786
Gene Ontology
(Biological Process)
Complete annatation
cytoplasmic pattern recognition receptor signaling pathway in response to virus [GO:0039528];
detection of virus [GO:0009597];
innate immune response [GO:0045087];
negative regulation of type I interferon production [GO:0032480];
positive regulation of defense response to virus by host [GO:0002230];
positive regulation of gene expression [GO:0010628];
positive regulation of granulocyte macrophage colony-stimulating factor production [GO:0032725];
positive regulation of interferon-alpha production [GO:0032727];
positive regulation of interferon-beta production [GO:0032728];
positive regulation of interleukin-6 production [GO:0032755];
positive regulation of interleukin-8 production [GO:0032757];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of transcription factor import into nucleus [GO:0042993];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
regulation of cell migration [GO:0030334];
regulation of type III interferon production [GO:0034344];
response to exogenous dsRNA [GO:0043330];
response to virus [GO:0009615];
RIG-I signaling pathway [GO:0039529]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
double-stranded DNA binding [GO:0003690];
double-stranded RNA binding [GO:0003725];
helicase activity [GO:0004386];
identical protein binding [GO:0042802];
single-stranded RNA binding [GO:0003727];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
actin cytoskeleton [GO:0015629];
bicellular tight junction [GO:0005923];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
ruffle membrane [GO:0032587]
Protein-protein interaction117121
Phylogenetic treeO95786
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: 6.947384765; Folds changes 16h: 2.527713583; Tested: tested;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: numerous RNA and DNA viruses
      Viral life cycle: translation; replication
      Mechanism related to antiviral activity: viral sensing; activation of IRFs
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. CD3-1.446396497054261.90739255702121e-050.000110485090774111
AZA vs. DISU0.07194116111610320.7772250767371670.976444104025318
AZA vs. IL7-0.1124870973337530.5620259047058520.999311006273513
AZA vs. SAHA-0.2996052056497140.2241151916977810.592495867232281
DISU vs. CD31.506457389199676.56714683592297e-050.000392830045256757
DISU vs. IL7-0.1937842891525830.4445985785160550.792708011651386
DISU vs. SAHA-0.3707548051764610.209624973055360.583418284317624
DMSO vs. AZA-0.075547951744230.6559543145351591
DMSO vs. CD31.360116295655193.63318875822305e-050.000182385833530924
DMSO vs. DISU-0.1492087206392990.5431954419196510.922153352453434
DMSO vs. IL7-0.02991349220694730.8691194827802730.971237921925134
DMSO vs. SAHA-0.2310928904827270.3314033323842110.685429886016738
HIV vs. Mock in Activation0.2179565947384070.7290023962938430.999983755607037
HIV vs. Mock in Latency0.1028229166862270.5363204441388830.999834320637052
IL7 vs. CD31.341949445395944.87552620231924e-050.000310866355531125
SAHA vs. CD31.12235984120730.00179658784720460.00590374593488298
SAHA vs. IL7-0.1907480738811830.4372387260383790.677823943843338
(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
1.8 0.005986407 1.2 0.116253914 1.7 0.132055749
(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) TRUE
(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 0.385461 0.00381747
(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
0.97 1.184 1.291 1.475 1.423
(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
218943_s_at 1.59 No upregulated in CD4+ cells

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
2LWD NMR - A=95-190.
2LWE NMR - A=95-190.
2QFB X-ray 3.0Å A/B/C/D/E/F/G/H/I/J=802-925.
2QFD X-ray 2.7Å A/B/C/D/E/F/G/H/I/J=802-925.
2RMJ NMR - A=792-925.
2YKG X-ray 2.5Å A=230-925.
3LRN X-ray 2.6Å A/B=803-923.
3LRR X-ray 2.1Å A/B=803-923.
3NCU X-ray 2.5Å A/B=792-925.
3OG8 X-ray 2.4Å A/B=802-925.
3ZD6 X-ray 2.8Å A=230-925.
3ZD7 X-ray 2.5Å A=230-925.
4AY2 X-ray 2.8Å A=239-925.
4BPB X-ray 2.5Å A=230-925.
4NQK X-ray 3.7Å A/B/C/D=1-200.
4ON9 X-ray 2.7Å A/B=230-793.
4P4H X-ray 3.4Å A/B/C/D/E/F/G/H=1-201.
5E3H X-ray 2.7Å A=232-925.
5F98 X-ray 3.2Å A/C/E/G/I/K=232-925.
5F9F X-ray 2.6Å A/C/E/G/I/K=232-925.
5F9H X-ray 3.1Å A/C/E/G/I/K=232-925.

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

HIV Partner Interaction Type PubMed
Vpr upregulates 25170834
26116899
retropepsin relocalizes 21084468

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa04623 Cytosolic DNA-sensing pathway - 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)
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