Human protein: interferon regulatory factor 3 isoform 1
Human protein sequence: MGTPKPRILPWLVSQLDLGQLEGVAWVNKSRTRFRIPWKHGLRQDAQQEDFGIFQAWAEATGAYVPGRDKPDLPTWKRNFRSALNRKEGLRLAEDRSKDPHDPHKIYEFVNSGVGDFSQPDTSPDTNGGGSTSDTQEDILDELLGNMVLAPLPDPGPPSLAVAPEPCPQPLRSPSLDNPTPFPNLGPSENPLKRLLVPGEEWEFEVTAFYRGRQVFQQTISCPEGLRLVGSEVGDRTLPGWPVTLPDPGMSLTDRGVMSYVRHVLSCLGGGLALWRAGQWLWAQRLGHCHTYWAVSEELLPNSGHGPDGEVPKDKEGGVFDLGPFIVDLITFTEGSGRSPRYALWFCVGESWPQDQPWTKRLVMVKVVPTCLRALVEMARVGGASSLENTVDLHISNSHPLSLTSDQYKAYLQDLVEGMDFQGPGES

HIV protein: capsid
Interaction type: interacts with
Description: HIV-1 CA mutants N74D and P90A fail to bind to CPSF6 and cyclophilins (Nup358 and CypA), respectively, and trigger innate sensors, leading to nuclear translocation of NFkappaB and IRF3, production of type 1 IFN and induction of an antiviral state
HIV protein sequence: PIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL

HIV protein: reverse transcriptase
Interaction type: activates
Description: The reverse-transcribed viral DNA by HIV-1 RT is the trigger of IRF3 activation and IFN-beta production in HIV-1 infected human monocytic cell line THP1
HIV protein sequence: PISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFRKQNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPPLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTNRGRQKVVTLTDTTNQKTELQAIYLALQDSGLEVNIVTDSQYALGIIQAQPDQSESELVNQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLVSAGIRKVL

HIV protein: Vif
Interaction type: degrades
Description: Virion-associated accessory proteins Vif and Vpr can independently degrade IRF-3. Eleven lysine residues in the N-terminal domain of IRF-3 are important for the Vif and Vpr mediated degradation
HIV protein sequence: MENRWQVMIVWQVDRMRIRTWKSLVKHHMYVSGKARGWFYRHHYESPHPRISSEVHIPLGDARLVITTYWGLHTGERDWHLGQGVSIEWRKKRYSTQVDPELADQLIHLYYFDCFSDSAIRKALLGHIVSPRCEYQAGHNKVGSLQYLALAALITPKKIKPPLPSVTKLTEDRWNKPQKTKGHRGSHTMNGH

HIV protein: Vif
Interaction type: induces cleavage of
Description: HIV-1 Vpr and Vif proteins cooperate with HIV-1 Vpu to induce IRF3 cleavage, although their individual effects are weaker than those of Vpu
HIV protein sequence: MENRWQVMIVWQVDRMRIRTWKSLVKHHMYVSGKARGWFYRHHYESPHPRISSEVHIPLGDARLVITTYWGLHTGERDWHLGQGVSIEWRKKRYSTQVDPELADQLIHLYYFDCFSDSAIRKALLGHIVSPRCEYQAGHNKVGSLQYLALAALITPKKIKPPLPSVTKLTEDRWNKPQKTKGHRGSHTMNGH

HIV protein: Vpr
Interaction type: degrades
Description: Virion-associated accessory proteins Vif and Vpr can independently degrade IRF-3. Eleven lysine residues in the N-terminal domain of IRF-3 are important for the Vif and Vpr mediated degradation
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: inhibits
Description: HIV-1 Vpr-mediated suppression of IFN induction is caused by failure of IRF-3 nucleus translocation
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Vpr
Interaction type: induces cleavage of
Description: HIV-1 Vpr and Vif proteins cooperate with HIV-1 Vpu to induce IRF3 cleavage, although their individual effects are weaker than those of Vpu
HIV protein sequence: MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQHIYETYGDTWAGVEAIIRILQQLLFIHFRIGCRHSRIGVTRQRRARNGASRS

HIV protein: Tat
Interaction type: induces phosphorylation of
Description: HIV-1 Tat-mediated downregulation of TRAF3 increases levels of phosphorylation of IRF3 and IRF7 in human microglial cells
HIV protein sequence: MEPVDPRLEPWKHPGSQPKTACTNCYCKKCCFHCQVCFITKALGISYGRKKRRQRRRAHQNSQTHQASLSKQPTSQPRGDPTGPKE

HIV protein: Vpu
Interaction type: co-localizes with
Description: HIV-1 Vpu co-localizes with IRF3 during HIV protein expression
HIV protein sequence: MQPIPIVAIVALVVAIIIAIVVWSIVIIEYRKILRQRKIDRLIDRLIERAEDSGNESEGEISALVEMGVEMGHHAPWDVDDL

HIV protein: Vpu
Interaction type: complexes with
Description: HIV-1 Vpu forms a stable and specific complex with IRF3 in HIV-1-infected cells, resulting in its specific sequestration within the endo-lysosomal compartment
HIV protein sequence: MQPIPIVAIVALVVAIIIAIVVWSIVIIEYRKILRQRKIDRLIDRLIERAEDSGNESEGEISALVEMGVEMGHHAPWDVDDL

HIV protein: Vpu
Interaction type: interacts with
Description: Interaction of HIV-1 Vpu with IRF3 governs the innate immune response of the host cell to HIV-1 infection
HIV protein sequence: MQPIPIVAIVALVVAIIIAIVVWSIVIIEYRKILRQRKIDRLIDRLIERAEDSGNESEGEISALVEMGVEMGHHAPWDVDDL

HIV protein: Vpu
Interaction type: induces cleavage of
Description: Caspase-8 and caspase-3 activity are required for HIV-1 Vpu-induced cleavage of IRF3 and HIV-1 infection also induces caspase-mediated IRF3 cleavage
HIV protein sequence: MQPIPIVAIVALVVAIIIAIVVWSIVIIEYRKILRQRKIDRLIDRLIERAEDSGNESEGEISALVEMGVEMGHHAPWDVDDL

HIV protein: Vpu
Interaction type: induces cleavage of
Description: HIV-1 Vpr and Vif proteins cooperate with HIV-1 Vpu to induce IRF3 cleavage, although their individual effects are weaker than those of Vpu
HIV protein sequence: MQPIPIVAIVALVVAIIIAIVVWSIVIIEYRKILRQRKIDRLIDRLIERAEDSGNESEGEISALVEMGVEMGHHAPWDVDDL

HIV protein: Vpu
Interaction type: induces cleavage of
Description: HIV-1 Vpu-induced cleavage of IRF3 is largely dependent on the ability of Vpu to interact with beta-TrCP, and mutation of the Vpu phosphorylation sites Ser52 and Ser56 greatly decreases the function of Vpu-induced IRF3 cleavage
HIV protein sequence: MQPIPIVAIVALVVAIIIAIVVWSIVIIEYRKILRQRKIDRLIDRLIERAEDSGNESEGEISALVEMGVEMGHHAPWDVDDL

HIV protein: Vpu
Interaction type: induces cleavage of
Description: Residue Asp121 is the primary site for Vpu-induced, caspase-mediated IRF3 cleavage, and the alternative site is residues Asp125 when Asp121 is mutated
HIV protein sequence: MQPIPIVAIVALVVAIIIAIVVWSIVIIEYRKILRQRKIDRLIDRLIERAEDSGNESEGEISALVEMGVEMGHHAPWDVDDL

HIV protein: Nef
Interaction type: activates
Description: HIV-1 Nef myristoylation is required for the activation of IRF-3, leading to the synthesis of IFNbeta in monocytes-derived-macrophages
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

HIV protein: Nef
Interaction type: activates
Description: The acidic cluster (residues 64-69) of HIV-1 Nef is required for IRF-3 activation and IFNbeta production
HIV protein sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC