Reporter : Zhang Qingdan
Publisher : Science & Technology Daily
Translation, editing : Gan Yung Chyan
/ KUCINTA SETIA
Image : Dynamic tracking of single Ebola virus invading cells. Courtesy of Wuhan Institute of Virology, Chinese Academy of Sciences
Ebola virus (EBOV) is one of the deadliest pathogens to humans. Viral infections cause severe hemorrhagic fever with a fatality rate of up to 90%. The entry of the virus into the host cell is the first step and the key step in the infection process but its invasion mechanism remains to be studied.
Recently, according to Cui Zongqiang, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences, who collaborated with Shan Yuping, a professor at Changchun University of Technology, and Shi Xinghua, a researcher at the National Nanoscience Center, based on single-particle force tracing, kinetic simulation, and single-particle fluorescence tracing technology, a single EBOV was revealed in real time dynamic process and mechanism of invasion.
The researchers first constructed a filamentous Ebola virus-like particle (EBO-VLP) and fluorescently labeled it. The filamentous structure EBO-VLP and wild-type EBOV have the same ability to invade cells, but there is no viral nucleic acid inside. Cannot be copied. The researchers used a dual-function PEG Linker to connect the EBO-VLP to the probe of the atomic force microscope, and monitored the dynamic process of endocytosis of a single EBO-VLP into the cell in real time through force tracking technology.
It was found that EBO-VLP can enter the cell through two modes, horizontal or vertical, with different forces and times corresponding to the two modes. The molecular dynamics simulation of the two modes also shows that EBO-VLP takes longer to enter the cell in the vertical direction than the horizontal mode, and requires more energy (that is, force). By analyzing the endocytosis signal detected by the computational force tracing, it is speculated that there are about nine receptor binding sites involved in viral endocytosis during the EBO-VLP invasion process. Real-time single-particle fluorescence tracing shows that EBO-VLP and cell giant cell markers can co-localize well, and have the same motion rate, trajectory, mean square displacement, etc. Giant cell inhibitors can significantly inhibit their invasion. Thus it is visually confirmed that EBO-VLP invades cells through the macrophage pathway.
The study dynamically analyzed the process of a single EBO-VLP invading the host cell in real time, revealing that the filamentous EBO-VLP entered the cell in two modes, horizontal and vertical, and the corresponding mechanics, space-time, energy, interaction with the receptor, fine invasion mechanisms such as pathways are of great significance for a deep understanding of the infection mechanism of EBOV, and also provide a basis for the development of antiviral pathways.
This research result has recently been published online in the journal "American Chemical Society-Nano". The research was funded by the National Key R&D Program, the National Natural Science Foundation of China, and the Pilot Project of the Chinese Academy of Sciences.
Related paper information: https://pubs.acs.org/doi/10.1021/acsnano.0c01739
No comments:
Post a Comment