ON August 8, Science Advances of the notable academic journal, Science, published the latest research findings of researcher Du Bing and his team composed of members from Shanghai Key Laboratory of Regulatory Biology and the Institute of Biomedical Sciences and School of Life Sciences at ECNU.
A kisspeptin/GPR54/calcineurin-mediated pathway for immune evasion
The collaborative work of the ECNU scientists found that antiviral innate immune response revealed a kisspeptin/GPR54/calcineurin-mediated pathway for immune evasion that is exploited by viruses through the negative feedback loop of TBK1 signaling. Bin Du and Professor Min Qian are the co-correspondent authors, Ph.D candidate Hongqing Huang and graduate students Qingqing Xiong and Ning Wang as co-first authors.
From left to right: Researcher Bing Du, Ph.D candidate Bing Huang and Professor Min Qian
Researcher Bing Du in his lab
They found a marked increase of kisspeptin in mouse serum during viral infection, which, in turn, impaired IFN-I production and antiviral immunity through the GPR54/calcineurin axis. Mechanistically, kisspeptin/GPR54 signaling recruited calcineurin and increased its phosphatase activity to dephosphorylate and deactivate TANK [tumor necrosis factor receptor-associated factor (TRAF) family member-associated NF-κB activator]–binding kinase 1 (TBK1) in a Ca2+-dependent manner.
Researcher Bin Du and his teamdemonstrated a new avenue to develop drugs targeting GPCRs to treat viral diseases, by inhibiting the kisspeptin/GPR54/calcineurin axis to enhance such antiviral responses. According to the journal, ECNU has become the leading institute in this field of scientific research,.
It is clear from the latest research findings that G protein–coupled receptor 54 (GPR54), the key receptor for the neuropeptide hormone kisspeptin, regulates puberty development and cancer metastasis; however, its role in the antiviral innate immune response is still unknown to scientists.
In addition, it provides new results into the functions and interactions of kisspeptin - a known neuropeptide hormone - in antiviral innate immune responses and its control mechanisms. They identified kisspeptin as a novel form of virus-induced neuropeptide hormones, which activates GPR54 to regulate IFN-I production and controls the intensity of antiviral innate immune responses.
Regulation mechanism of kisspeptin/GPR54
The research was funded by key actors of China's science and technology development programs, including the Ministry of Science and Technology of the People’s Republic of China, National Natural Science Foundation of China, the Shanghai Science and Technology Committee and JORISS.
Group photo of Researcher Bing Du's team
In conclusion, the newfound results of the ECNU team found that targeting GPCRs not only plays a vital role when it comes to the treatment of viral diseases since about 50% of the current therapeutic drugs on the market, whether directly or indirectly, target GPCRs as the main source of antiviral responses.
To go along with Bin Du and his team, Professor Mingyao Liu’s team at ECNU has already published significant research in renowned journals like Science, Nature, Nature Medicine, Nature Biotechnology; they both focus on methods that target GPCRs by inhibiting the kisspeptin/GPR54/calcineurin axis to enhance antiviral response and have both published their work in world-famous journals like Science Advances, Cancer Research, Journal of Immunology, Cellular& Molecular Immunology, Journal of Biological Chemistry.
The Shanghai Key Laboratory of Regulatory Biology of ECNU is also strengthening cooperation nationwide with top medical institutes in the field of treating virus diseases, combining their cutting-edge scientific discoveries with clinical treatment and working together to provide new concepts for applied and theoretical scientific research.
Edited by Linlan Zhang Proofread by Mayfield Joshua Reviewed by Wenjun Guo