Inhibition of host IKBKE by virus (kw:KW-1224)

Upon activation of viral RNA sensors, such as RIG-I-like receptors, IKK-epsilon associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli.

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Several viruses including arenaviruses or ebola virus interact directly with and inhibit IKBKE/IKK-epsilon to prevent IRFs activation. Engagement of arenavirus nucleocapsid protein seems to sequester IKKepsilon in an inactive complex while VP35 from ebola virus interferes with the interaction between Ikkepsilon and IRF3/IRF7 substrates.

Inhibition of MDA5/RIG-I pathway Inhibition of RIG-I
Inhibition of MDA5
Inhibition of MAVS
Inhibition of IKKepsilon
Inhibition of host IRF3
Inhibition of host IRF7
Links Uniprot Keyword: KW-1224
GO ontology: GO:0039724
Virus -Arenaviruses
(Arenaviridae, Arenavirus)

-Ebolavirus
(Filoviridae, Ebolavirus )

-Dengue virus
(Flaviviridae, Flavivirus )

Matching UniProtKB/Swiss-Prot entries

(all links/actions below point to uniprot.org website)

32 entries grouped by strain

1 entry

Alethinophid 1 reptarenavirus (isolate AlRrV1/Boa/USA/BC/2009) (Golden Gate virus) reference strain

NCAP_GOGV Nucleoprotein (Nucleocapsid protein) (Protein N)

1 entry

Bat coronavirus HKU4 (BtCoV) (BtCoV/HKU4/2004) reference strain

ORF4B_BCHK4 Non-structural protein ORF4b (ORF4b)

1 entry

Bat coronavirus HKU5 (BtCoV) (BtCoV/HKU5/2004) reference strain

ORF4B_BCHK5 Non-structural protein ORF4b (ORF4b)

1 entry

Cupixi mammarenavirus (isolate Rat/Brasil/BeAn 119303/1970) (CPXV) reference strain

NCAP_CPXVB Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Lassa virus (strain Mouse/Sierra Leone/Josiah/1976) (LASV) reference strain

NCAP_LASSJ Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Latino mammarenavirus (isolate Rat/Bolivia/MARU 1924/1965) (LATV) reference strain

NCAP_LATVB Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Lymphocytic choriomeningitis virus (strain Armstrong) (LCMV) reference strain

NCAP_LYCVA Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012) (MERS-CoV) (Betacoronavirus England 1) reference strain

ORF4B_MERS1 Non-structural protein ORF4b (ORF4b)

1 entry

Oliveros mammarenavirus (isolate Mouse/Argentina/RIID 3229/1990) (OLVV) reference strain

NCAP_OLVVA Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Pirital mammarenavirus (isolate Rat/Venezuela/VAV-488/1995) (PIRV) reference strain

NCAP_PIRVV Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Tacaribe virus (strain Franze-Fernandez) (TCRV) reference strain

NCAP_TACVF Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Whitewater Arroyo mammarenavirus (isolate Rat/United States/AV 9310135/1995) (WWAV) reference strain

NCAP_WWAVU Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus) reference strain

VP35_EBOZM Polymerase cofactor VP35 (Ebola VP35) (eVP35)

1 entry

Allpahuayo mammarenavirus (isolate Rat/Peru/CLHP-2472/1997) (ALLV)

NCAP_ALLVP Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Bear Canyon mammarenavirus (isolate Mouse/United States/AV A0070039/2000) (BCNV)

NCAP_BCNVU Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Chapare mammarenavirus (isolate Human/Bolivia/810419/2003)

NCAP_CHAVB Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Guanarito mammarenavirus (isolate Human/Venezuela/NH-95551/1990) (GTOV)

NCAP_GTOVV Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Ippy mammarenavirus (isolate Rat/Central African Republic/Dak An B 188 d/1970) (IPPYV)

NCAP_IPPYV Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Junin mammarenavirus (JUNV) (Junn mammarenavirus)

NCAP_JUNIN Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Lassa virus (strain GA391) (LASV)

NCAP_LASSG Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Lymphocytic choriomeningitis virus (strain WE) (LCMV)

NCAP_LYCVW Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Machupo virus (MACV)

NCAP_MACHU Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Mobala mammarenavirus (isolate Rat/Central African Republic/Acar 3080/1983) (MOBV)

NCAP_MOBVC Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Mopeia virus (MOPV)

NCAP_MOPEI Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Parana mammarenavirus (isolate Rat/Paraguay/12056/1965) (PARV) (Paran mammarenavirus)

NCAP_PARVP Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Pichinde mammarenavirus (PICV) (Pichind mammarenavirus)

NCAP_PIARV Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Reston ebolavirus (strain Philippines-96) (REBOV) (Reston Ebola virus)

VP35_EBORE Polymerase cofactor VP35

1 entry

Reston ebolavirus (strain Reston-89) (REBOV) (Reston Ebola virus)

VP35_EBORR Polymerase cofactor VP35

1 entry

Sabia mammarenavirus (isolate Human/Brasil/SPH114202/1990) (SABV) (Sabi mammarenavirus)

NCAP_SABVB Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Sudan ebolavirus (strain Human/Uganda/Gulu/2000) (SEBOV) (Sudan Ebola virus)

VP35_EBOSU Polymerase cofactor VP35

1 entry

Tamiami mammarenavirus (isolate Rat/United States/W 10777/1964) (TAMV)

NCAP_TAMVU Nucleoprotein (EC 3.1.13.-) (Nucleocapsid protein) (Protein N)

1 entry

Zaire ebolavirus (strain Kikwit-95) (ZEBOV) (Zaire Ebola virus)

VP35_EBOZ5 Polymerase cofactor VP35 (Ebola VP35) (eVP35)