title: HTLV-1 Tax impairs K63-linked ubiquitination of STING to evade host innate immunity.
abstract: The cellular antiviral innate immune system is essential for host defense and viruses have evolved a variety of strategies to evade the innate immunity. Human T lymphotropic virus type 1 (HTLV-1) belongs to the deltaretrovirus family and it can establish persistent infection in human beings for many years. However, how this virus evades the host innate immune responses remains unclear. Here we report a new strategy used by HTLV-1 to block innate immune responses. We observed that stimulator of interferon genes (STING) limited HTLV-1 protein expression and was critical to HTLV-1 reverse transcription intermediate (RTI) ssDNA90 triggered interferon (IFN)-β production in phorbol12-myristate13-acetate (PMA)-differentiated THP1 (PMA-THP1) cells. The HTLV-1 protein Tax inhibited STING overexpression induced transcriptional activation of IFN-β. Tax also impaired poly(dA:dT), interferon stimulatory DNA (ISD) or cyclic GMP-AMP (cGAMP) -stimulated IFN-β production, which was dependent on STING activation. Coimmunoprecipitation assays and confocal microscopy indicated that Tax was associated with STING in the same complex. Mechanistic studies suggested that Tax decreased the K63-linked ubiquitination of STING and disrupted the interactions between STING and TANK-binding kinase 1 (TBK1). These findings may shed more light on the molecular mechanisms underlying HTLV-1 infection.
authors.affiliation: Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Yang
authors.affiliation: Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, China. Electronic address: huiwang65@yeah.net.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, China. Electronic address: ybb@mail.ustc.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
mesh_terms: D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000235:genetics* / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D008239:Lysine / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D011067:Poly dA-dT / Q000494:pharmacology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000276:immunology; D048348:Reverse Transcription; D015398:Signal Transduction; D000074084:THP-1 Cells; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D054875:Ubiquitination; D000099197:STING Protein
chemical_list: D016356:Gene Products, tax; D016899:Interferon-beta; D008239:Lysine; D008565:Membrane Proteins; D009712:Nucleotides, Cyclic; D011067:Poly dA-dT; D017346:Protein Serine-Threonine Kinases; D013755:Tetradecanoylphorbol Acetate; C532857:STING1 protein, human; D000099197:STING Protein; C584311:cyclic guanosine monophosphate-adenosine monophosphate; C514970:tax protein, Human T-lymphotrophic virus 1; C403191:TBK1 protein, human
keywords: HTLV-1; Innate immune responses; STING; Signal transduction; Tax; Ubiquitination