HSV-2 shell particles: Progress in the study of the assembly mechanism of herpes virus nuclear case.

Recently, The Chinese Academy of Sciences academician Rao Zi and team researcher Wang Xiangxi, Hunan Normal University professor Liu Hongrong, researcher of the Institute of Biophysics of the Chinese Academy of Sciences Zhang Xinying, Professor Wang Junzhi of the China Institute of Food and Drug Inspection, etc., for the first time, analyzed the herpes virus alpha family type 2 herpes simplex virus (HSV-- 2) The 3.1A atomic resolution structure of the nuclear coat shell clarifies the complex interaction mode and fine structural information of the nuclear shell protein, and puts forward the assembly mechanism of the nuclear shell of herpes virus, which lays the foundation for further study of the assembly of the nuclear shell and envelope protein of the virus and the anti-viral treatment of herpes virus.
research on Cryo-EM structure of a Herpesvirus capsid at 3.1? was published April 6 in Science.
herpes virus is a widespread spread of the world's virus, including a variety of virus species, can infect humans and many mammals.
herpes virus can cause oral and genital herpes, chickenpox, shingles and other diseases after infection with the human body, and even cause a variety of immune system diseases, encephalitis and cancer.
herpes virus is widespread worldwide, for example: world Health Organization January 2017 data show that about 4.2 billion people under the age of 50 (about 80%) worldwide are infected with the herpes simplex virus (HSV-1 and HSV-2).
herpes virus has a unique latent-reactivation mechanism that shuts down genes in most of its active states, turns on a specific minority of genes at specific incubation stages, and resumes activity under appropriate conditions and re-enters the proliferation process.
this latent-reactivation mechanism makes it difficult to completely cure the disease caused by herpes virus infection, and patients usually carry the virus for life.
herpes virus is about 200nm in diameter and contains a surface cystic membrane, protein intermediate layer (tegument proteins), nucleoshell particles, and a dna core four-layer structure.
, the diameter of the nuclear shell is about 125nm, in the virus replication, assembly, maturation and infection process plays a very important role.
nuclear shell contains A, B, C three categories, three types of nuclear shell are non-standard positive twenty-dozen faces.
the interior of the Type A nuclear shell is empty and does not contain other proteins and viral genomes;
over the past 20 years, many scientists have tried to analyze the three-dimensional structure of the herpes virus's nuclear shell using cryoscope technology, but the ice is too thick, signal-to-noise ratio reduced and the Ewald ball effect is too large, creating a technical bottleneck for the reconstruction of high-resolution information.
the study took HSV-2 shell particles as the research object, used the newly developed calculation method of frozen electron mirror single particle reconstruction "zoning calculation method" and "underfocus value correction method", analyzed 3.1? nuclear shell B particles, and constructed a structural model, analyzed in detail the interaction relationship between the structural proteins in the nuclear shell, and explained the mechanism of the early assembly of the nuclear shell of the virus.
the application of the refactoring method for "large-scale particles", the application range of cryoscope structure analysis is further popularized, and the single-particle reconstruction of superprotein complex at the supercell level of giant viral particles or subcellular systems can achieve near-atomic resolution, which will further promote the progress and development of structural biology.
In view of the importance and conservatism of nuclear shell structure in herpes virus, the drug design and molecular screening of herpes virus nuclear shell structure, the institute's analysis of the nuclear shell structure can provide a structural basis for the development of broad-spectrum drugs.
Rao Zi and team doctoral students Yuan Shuai, Wang Jialing, Zhang New Deal group doctoral student Zhu Dongjie as the paper co-first author.
Wang Xiangxi, Zhang Xinying, Liu Hongrong, Wang Junzhi, Rao Zi and co-authors of the paper. Wang Nan, Ph.D. gao Qiang, graduate student of the
Institute of Biophysics, and Chen Wenxuan and Tang Hao, graduate students of Hunan Normal University, participated in the research.
the research has been supported by the National Natural Science Foundation of China, the National Key Basic Research and Development Program, and the Chinese Academy of Sciences' strategic leading science and technology projects.
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