A molecular sensor that can specifically recognize and isolate only infected cells in the early stage of avian flu infection has been developed.
Professor Jun-seok Lee’s team from the Department of Pharmacology at Korea University College of Medicine developed a new ‘T-shaped’ luminescent molecular structure (Extended and Ligating Imidazolyl Fluorophore: EliF) that exhibits fluorescence sensitively to external stimuli through joint research with Professor Lee Dong-hwan of the Department of Chemistry at Seoul National University. Among these derivatives, we succeeded in developing a molecule that selectively responds to microscopic environmental changes in the endoplasmic reticulum. This molecule selectively emits light in infected cells in the early stage of avian influenza virus infection, making it possible to selectively distinguish only infected cells.
Existing avian influenza infection diagnosis research has been limited to a virus gene sequence-specific PCR technique and detection technique using an antibody once morest avian influenza virus protein. This is a method of directly observing the virus regardless of the subject it is infected with.
Viruses actively interact and multiply with host cells, and in this process, there is a difference in susceptibility to infection depending on the genetic and developmental characteristics of the host cell. The research team reported different patterns of avian influenza infection in cells derived from multiple organs and in cell line models with different genetic backgrounds. Proteomic analysis has been studied.
The research team designed an EliF phosphor with a ‘T-shape’ that responds sensitively to changes in the surrounding environment by controlling the structural flexibility of the fluorescent molecule, and built a library of similar structures. During the study, it was strangely observed that molecules gather in the shape of an ER in living cells. In general, when a drug is connected to a phosphor, it is possible to target various organelles in the cell, but an example of targeting the ER by the characteristic of the phosphor has been reported in academia. no bar
Furthermore, we performed chemoproteomics profiling and bioinformatics analysis to identify proteins that interact with EliF in cells, and revealed that EliF molecules selectively interact with proteins related to ER stress. The ER is an organ where protein synthesis occurs, and in diseases such as neurodegenerative diseases, diabetes, and viral infections, a physiological response called ER stress occurs. The aggregation and accumulation of abnormal folding proteins occur in the endoplasmic reticulum, and with this in mind, we demonstrated by flow cytometry that the EliF molecule can measure the initial change in avian influenza virus infection as a fluorescence change at the cellular level. A new analysis technology has been developed to study the characteristics of host cells susceptible to infection by detecting and isolating only cells infected with avian influenza virus in complex cells and tissues.
In addition, unlike the existing infection diagnosis method, which took several days or more, the method developed by the research team has great significance in that it can quantify the degree of infection within 24 hours through fluorescence intensity at the single cell level.
Professor Jun-seok Lee, the research director, said, “Using the EliF molecule developed this time, it is possible to fractionate cells that show a high infection rate in the early stage of avian influenza virus infection in live cells at the single-cell level and study their characteristics.” “The research will be an important key to understanding the mechanism of infection and developing therapeutics,” he said.
This research was led by co-first author Dr. Kang Tae-won from Seoul National University, Dr. Mamunulhak from Korea University, and corresponding author Jun-seok Lee from Korea University, and Professor Lee Dong-hwan from the Department of Chemistry at Seoul National University. ), the mid-level research support project, and the Samsung Future Technology Promotion Project. The research results are the sister journal Nature, a world-class international academic journal.
