Kaposi Sarcoma-associated Herpesvirus Degrades Cellular Toll-Interleukin-1 Receptor Domain-containing Adaptor-inducing β-Interferon (TRIF)
| Autor: | Florencia Meyer, Erica Ehlers, Rachel Gubbels, Humera Ahmad, Thomas Waterbury, Rongtuan Lin, Luwen Zhang |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Proteasome Endopeptidase Complex
Interferon Regulatory Factor-7 viruses Down-Regulation Biology Virus Replication Biochemistry Immediate early protein Cell Line Immediate-Early Proteins Viral Proteins Ubiquitin Interferon medicine Humans Gene Regulation Molecular Biology Immune Evasion RNA Double-Stranded Signal transducing adaptor protein Cell Biology biochemical phenomena metabolism and nutrition Virology Immunity Innate Protein Structure Tertiary Toll-Like Receptor 3 Virus Latency Cell biology Ubiquitin ligase Toll-Like Receptor 4 Adaptor Proteins Vesicular Transport TRIF Herpesvirus 8 Human Interferon Type I Trans-Activators biology.protein Signal transduction Interferon type I medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 286:7865-7872 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m110.191452 |
| Popis: | Kaposi sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Toll-interleukin-1 receptor (TIR) domain-containing adaptor-inducing β-interferon (TRIF, also called TIR-domain-containing adaptor molecule-1 (TICAM-1)) is a signaling adaptor molecule that is critically involved in the Toll-like receptor 3 (TLR-3) and TLR-4 signaling pathways for type I interferon (IFN) production, a key component of innate immunity against microbial infection. In this report, we find a new mechanism by which RTA blocks innate immunity by targeting cellular TRIF. RTA specifically degrades TRIF by shortening the half-life of TRIF protein. This RTA-mediated degradation is at least partially mediated through the ubiquitin-proteasome pathway because proteasome inhibitors as well as knockdown of cellular ubiquitin expression alleviate the degradation. RTA may not directly interact with TRIF and may activate TRIF degradation indirectly through an unknown mediator(s). RTA targets multiple regions of TRIF and may use its ubiquitin ligase domain for the degradation. In addition, physiological levels of TRIF protein are down-regulated during KSHV lytic replication when RTA is expressed. Finally, RTA down-regulates double-stranded RNA-initiated activation of TLR-3 pathway, in the absence of degradation of IFN regulatory factor 7 (IRF-7). Taken together, these data suggest that KSHV employs a novel mechanism to block the innate immunity by degrading TRIF protein. This work may contribute to our understandings on how KSHV evades host immunity for its survival in vivo. |
| Databáze: | OpenAIRE |
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