Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000815
UniProt IDQ96C10
Primary gene name(s)DHX58
Synonym gene name(s)D11LGP2E, LGP2
Protein nameProbable ATP-dependent RNA helicase DHX58
Protein functionActs as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on DDX58/RIG-I signaling may involve the following mechanisms: competition with DDX58/RIG-I for binding to the viral RNA, binding to DDX58/RIG-I and inhibiting its dimerization and interaction with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1 thereby inhibiting activation of interferon regulatory factor 3, IRF3. Its positive regulatory role may involve unwinding or stripping nucleoproteins of viral RNA thereby facilitating their recognition by DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses, and also to the bacterial pathogen Listeria monocytogenes. Can bind both ssRNA and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5'-triphosphorylated RNA, although it can recognize RNA lacking a 5'-triphosphate. {ECO:0000269|PubMed:16116171, ECO:0000269|PubMed:17020950, ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18411269, ECO:0000269|PubMed:19208642, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19278996, ECO:0000269|PubMed:19380577, ECO:0000269|PubMed:21187438, ECO:0000269|PubMed:21525357}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:19380577}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q96C10
Gene Ontology
(Biological Process)
Complete annatation
defense response to virus [GO:0051607];
innate immune response [GO:0045087];
negative regulation of innate immune response [GO:0045824];
negative regulation of MDA-5 signaling pathway [GO:0039534];
negative regulation of RIG-I signaling pathway [GO:0039536];
negative regulation of type I interferon production [GO:0032480];
positive regulation of MDA-5 signaling pathway [GO:1900245];
positive regulation of RIG-I signaling pathway [GO:1900246];
positive regulation of type I interferon production [GO:0032481];
regulation of innate immune response [GO:0045088];
response to virus [GO:0009615]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
DNA binding [GO:0003677];
double-stranded RNA binding [GO:0003725];
helicase activity [GO:0004386];
single-stranded RNA binding [GO:0003727];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737]
Protein-protein interaction122553
Phylogenetic treeQ96C10
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. CD3-1.308652323897860.0001031366094834670.000495529161024807
AZA vs. DISU-0.3631843356571630.1823904622380430.76836786777268
AZA vs. IL7-0.1937016125736870.4398897781299610.999311006273513
AZA vs. SAHA-0.4354525983486750.2134917880626730.581996326760701
DISU vs. CD30.9327753754332960.01245538681928850.0348593577634524
DISU vs. IL70.1591308555896190.5593299168031420.857109172095007
DISU vs. SAHA-0.06867560766161430.8520791370243050.960232245593492
DMSO vs. AZA-0.003099272013161460.9879990008327651
DMSO vs. CD31.29540705506557.76197917072841e-050.000359134570660391
DMSO vs. DISU0.3585615603411530.1474376005233280.643278702920251
DMSO vs. IL7-0.1832951985323020.3766160654247510.832079017986843
DMSO vs. SAHA-0.4367704165817340.1712787307280520.500403128401333
HIV vs. Mock in Activation0.7600806061173980.2281337611611540.999983755607037
HIV vs. Mock in Latency0.1934908681919990.2466054798970710.999834320637052
IL7 vs. CD31.118647680333070.0008233138899518270.00359184088661183
SAHA vs. CD30.851682412548650.03713099343517330.0776269188528497
SAHA vs. IL7-0.2429527910084780.4861301231568920.717988246880228
(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) 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 1.27325 0.000305467
(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
0.05 0.005

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
unknown unknown unknown unknown unknown
(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
2RQA NMR - A=546-678.
2W4R X-ray 2.6Å A/B/C/D=537-678.
3EQT X-ray 2.0Å A/B=541-678.

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

HIV Partner Interaction Type PubMed
HIV-1 virus replication enhanced by expression of human gene 18976975

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)