On May 14, the team of Professor Cheng Xiaofei of the College of Plant Protection of Northeast Agricultural University and the team of Professor Xiang Wensheng published a research paper entitled "The 6-kilodalton peptide 1 in plant viruses of the familyPotyviridaeis a viroporin" in the PNAS, Proceedings of the National Academy of Sciences. In this study, viral viroporins were discovered in plant viruses for the first time, and the role of viroporins in viral infection was analyzed.
Virophorins are a class of viruses encoding small proteins (typically less than 100 amino acids) that function as ion channels through homologous oligomerization. Virophorins are essential for viruses to complete their life cycles, so they have been key molecular targets for the development of antiviral drugs and live attenuated vaccines. Previously, virophorin was only found in some animal viruses, such as hepatitis C virus p7 protein, influenza A virus M2 protein, Ebola virus δ peptide, human astrovirus XP protein, and novel coronavirus E protein. Whether other types of viruses, including plant viruses, encode viroporin, has been an open question. Potyviridae is the largest plant RNA viridae family, and many viruses in this family cause serious diseases in crops worldwide, causing significant economic losses. Viruses in this family encode a highly conserved small protein (6K1) of only 6~7 kDa between P3 and CI, but its exact function has been unknown for more than three decades since its discovery. In this study, turnip mosaic virus (TuMV) was used as the research object, and TuMV 6K1 was found to form multimers in the endoplasmic reticulum, and combined with AI-assisted structure modeling and protein biochemical analysis, TuMV 6K1 was found to form a pentamer with a central hydrophobic channel. Further studies have found that TuMV 6K1 can increase the cell membrane permeability of Escherichia coli and Nicola benthami, and can partially compensate for the yeast mutants with missing potassium ion channels, and mutant amino acids related to polymerization in TuMV 6K1 can inhibit viral proliferation, indicating that TuMV 6K1 is a functional viroporecin. In addition, this study also demonstrated that 6K1 or its homologous 7K protein encoded by other viruses of the same family can increase cell membrane permeability and partially compensate for yeast mutants with missing potassium channels. In conclusion, this study not only revealed the function of 6K1 protein and its homologous 7K protein in Y viridae virus, but also deepened the understanding of the pathogenic mechanism of the virus in this family, and laid a solid theoretical foundation for the subsequent screening and design of antiviral drugs targeting 6K1 ion channels.
Prediction structure of TuMV 6K1 pentamerThis study was supported by the National Natural Science Foundation of China for Outstanding Young Scholars, the National Key Research and Development Program of China, the Natural Science Foundation of Heilongjiang Province, and the "Young Leading Talents" Support Program of Northeast Agricultural University. Professor Cheng Xiaofei, Associate Professor Wu Xiaoyun and Professor Xiang Wensheng are the corresponding authors of this paper, Chai Mengzhu and Li Lei, doctoral students graduated from the College of Plant Protection, Professor Li Yong of the College of Life Sciences are the co-first authors, and Northeast Agricultural University is the corresponding unit. Yingshuai Yang, Yuting Wang, Xue Jiang and Yameng Luan, graduate students from the molecular plant virology team at Northeast Agricultural University, participated in the study, and the study was supported by the team of Professor Aiming Wang from the London Research & Development Centre of Agriculture and Agri-Food Canada (AAFC), Professor Fangfang Li of the Chinese Academy of Agricultural Sciences, and researcher Hongguang Cui from Hainan University. Cheng Xiaofei's profile: Ph.D., doctoral supervisor, third-level professor of Northeast Agricultural University, vice president of the College of Plant Protection, high-level talent (class B) in Heilongjiang Province, "Outstanding Scholar JC1" of high-level talent of Dongnong Scholars Program. He has published more than 60 papers in journals such as Nature Communications, Plant Cell, Trends in Microbiology, Journal of Virology, etc. as the first or corresponding author. As the first person to complete the award, he won the Youth Science and Technology Award of the Chinese Agricultural Society and the first prize of the Heilongjiang Provincial Plant Protection Science and Technology Scientific Research Category. Welcome outstanding PhDs who love plant antiviral immunity to join our team (please send your cover letter, resume, list of papers and other relevant materials to E-mail:[email protected]). Wu Xiaoyun's profile: Ph.D., master's supervisor, selected for the Heilongjiang Provincial Outstanding Young Teacher Basic Research Support Program, academic backbone of the Dongnong Scholars Program, mainly engaged in plant virology research, and published more than 30 papers in Nature Communications, Journal of Virology, Traffic and other journals as the first or corresponding author. Xiang Wensheng profile: Ph.D., doctoral supervisor, second-level professor of Northeast Agricultural University, young and middle-aged experts with outstanding contributions to the national "Millions of Talents Project", "Young and Middle-aged Scientific and Technological Innovation Leading Talents" of the Ministry of Science and Technology, and outstanding talents and innovation teams of agricultural scientific research of the Ministry of Agriculture. Realized the fermentation and semi-synthesis of 4 new microorganisms and the industrialization of 7 products, and obtained 8 new drug certificates. As the first author or corresponding author, he has published more than 300 SCI papers in journals such as Nature Biotechnology and Nature Communications. As the first completer, he won 1 second prize of National Science and Technology Invention Award and 4 first prizes of Heilongjiang Province Science and Technology Invention Award. Original link: https://www.pnas.org/doi/10.1073/pnas.2401748121 Source: Northeast Agricultural University report
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