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: Jie Wang, Shuai Yang, Lu Liu, Hui Wang, Bo Yang
• Journal: Virus research (Virus Res) Vol. 232 Pg. 13-21 (03 15 2017) ISSN: 1872-7492 [Electronic] Netherlands
• PMID: 28119118 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Gene Products, tax
• Membrane Proteins
• Nucleotides, Cyclic
• STING1 protein, human
• cyclic guanosine monophosphate-adenosine monophosphate
• tax protein, Human T-lymphotrophic virus 1
• Poly dA-dT
• Interferon-beta
• Protein Serine-Threonine Kinases
• TBK1 protein, human
• Lysine
• Tetradecanoylphorbol Acetate

Topics

• Gene Expression Regulation
• Gene Products, tax (genetics, immunology)
• Human T-lymphotropic virus 1 (genetics, immunology)
• Humans
• Immune Evasion
• Immunity, Innate
• Interferon-beta (genetics, immunology)
• Lysine (metabolism)
• Macrophage Activation (drug effects)
• Membrane Proteins (genetics, immunology)
• Nucleotides, Cyclic (pharmacology)
• Poly dA-dT (pharmacology)
• Protein Binding
• Protein Serine-Threonine Kinases (genetics, immunology)
• Reverse Transcription
• Signal Transduction
• THP-1 Cells
• Tetradecanoylphorbol Acetate (pharmacology)
• Ubiquitination