动物实验,抗病毒 z-bo 2020-09-29 386

　　NatureCellBiology ("ature? Cell Biology") published a research paper entitled "Hipposignalinggovernscytosolicnucleicacidinging through YAP/TAZ-mediated TBK1 blockade" by Xu Pinglong's laboratory of the Institute of Biological Sciences, Zhejiang University in the form of an article, nutrition or contact of host cells The state is Hippo route. It shows that it is regulated by the function and mechanism of antiviral spontaneous immune response.

　　The study of antiviral host defense mechanism is one of the main frontiers in the development of international biomedicine and has important scientific cognitive value and potential applications. So far, how the microenvironment and nutrition, metabolism, and physical state of host cells affect the cytoplasmic nucleic acid recognition mechanism and antiviral host defense is a very basic and important issue. , There is no detailed research in the world. Xu Pinglong’s laboratory found that in environments with nutritional/energy stress or inhibited contact, host cells have significantly enhanced ability to recognize viral nucleic acids and anti-viral defenses. This regulation depends on the main kinase Lats 1/2 of the Hippo-YAP pathway in the cell. From the point of view of molecular mechanism, the Hippo pathway effector protein YAP/TAZ is a natural TBK1 inhibitory protein whose function is independent of transcription regulation ability. It forms a complex with TBK1, which is the activation complex of TBK1 and TBK. Can effectively prevent K63 ubiquitination modification. form. Therefore, the activation of the hippo pathway caused by nutritional stress or cell-cell contact conditions modifies YAP/TAZ through phosphorylation to inactivate and degrade it, thereby inhibiting the host's defense mechanism against viruses. Can be released. Similarly, CRISPR-mediated YAP/TAZ knockdown significantly enhanced the host cell's antiviral defense capabilities, but the expression of non-transcribed YAP variants significantly weakened the cell and zebrafish's virus resistance. I will. therefore,

　　'S research first proposed the key regulatory functions of physical contact state on cellular nutritional stress and viral host defense, and analyzed its molecular basis under the control of the Hippo-YAP pathway. The study also defined the physiological function of the masking pathway in antiviral defense, as well as the new function and mechanism of YAP/TAZ, and its function has nothing to do with its transcription ability. This work has further improved the zebrafish host defense research model established in the laboratory. These discoveries and new technologies provide a new theoretical and experimental basis for understanding the host anti-virus defense mechanism and developing anti-virus prevention methods.