Scientists find the "on-off" of antiviral immune cells

How does "Once having identified viruses, natural immune cells would response" happen? Academician Cao Xuetao research team from Chinese Academy of Engineering found that DNA methylation enzyme Dnmt3a can make natural immune cells in highly sensitive state against virus infection. Once identifying viruses, they can produce significant interferon and start antiviral innate immune response. The study was published in the UK journal Nature Immunology. Many other recombinant proteins against viruses are also studied.

In order to figure out why the natural immune cells have the function of rapid resistance "virus invasion", the research team first made the natural immune cells infected with virus and analyzes molecular changes of infected cells expression. They chose "epigenetic regulation elements" which can determine gene expression by regulation of DNA methylation as the breakthrough point. By screening, they discovered that DNA methyltransferase Dnmt3a can promote innate immune cells to efficiently release type I interferons.

"Later they got genome-wide DNA of natural immune cells and ascertained the methylation status of the DNA chain at single nucleotide level and drew 'spectrum'. Take this spectrum as a benchmark, we conducted a study of the mechanism." Said Cao Xuetao. He and immunization doctoral student Li Xia at Zhejiang University, Zhang Qian from Key Laboratory of Medical Immunology at second Military Medical University immunization State discovered the specific effect path: Dnmt3a is bound to HDAC9 distal promoter region and maintains the DNA hypermethylation in the region, thereby antagonizing H3K27me3 in the region and promoting the active histone modification levels of proximal promoter to maintain high HDAC9 expression. Highly-expressed HDAC9 then efficiently induce type I interferon through a certain mechanism, starting antiviral innate immune response. The researchers used various recombinant proteins including recombinant mouse proteins to ensure the research results.

Studies have shown that DNA methylation can maintain high expression of key molecules in antiviral signaling pathway, preparing to efficiently and timely start antiviral immune response native cell during virus invasion. The findings reveal a novel epigenetic mechanism of antiviral immune response and also propose new potential molecular targets for prevention and treatment of viral infectious diseases.

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