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One-Third of Human Food Depends on Bees! The National Synchrotron Radiation Research Center Cracks the Structure of Honeybee-Infecting Viruses to Protect Bee Colonies
2023/02/16


With the long-term support of the National Science and Technology Council, the research team led by Dr. Chun-Jung Chen and Dr. Nai-Chi Chen of the National Synchrotron Radiation Research Center (NSRRC) has after nearly five years achieved a world first in identifying the capsid protein structure and function of the Lake Sinai Honeybee-Affecting Virus, as well as the dynamic assembly process for virion formation. This research is of great significance for developing natural antiviral medicines for bees, and the results were published in the prestigious journal Nature Communications on February 1.

According to the Food and Agriculture Organization (FAO) of the United Nations, nearly one-third of the world's agricultural crops rely on bee pollination. In the past few decades, bee populations around the world have plummeted because their habitats have been greatly reduced, which affects not only crop pollination but also food supply for human beings. In 2006, the United States named the mysterious disappearance of bee populations "Colony Collapse Disorder." Previous studies have revealed that in addition to human factors and environmental changes, one of the major causes of Colony Collapse Disorders is viral infection, which could cause severe damage to a bee's brain, central nervous system, and wings, affecting its ability to harvest and return to the nest, or even resulting in death.

The Lake Sinai virus is a recently discovered and highly contagious honeybee-infecting virus that could cause a large number of bee deaths in a short period of time, and for which there is currently no cure. The current method to control transmission involves large-scale incineration of infected hives, which hugely impacts beekeeping. Another method is the use of pesticide; however, this approach is likely to cause environmental pollution; the chemical residues in honey may exacerbate the food safety problem. In order to improve the survival rate of honeybees, scientists are eager to gain a full understanding of the virus and the mechanism of infection so that antiviral drugs can be developed to block the spread of the virus and minimize damage.

The research team used the protein crystallography and small-angle scattering techniques of the high-intensity X-ray endstations at NSRRC in Taiwan and SPring-8 in Japan, in partnership with the SLAC National Accelerator Laboratory of Stanford University in the United States, as well as Drs. Meng-Chiao Ho and Chun-Hsiung Wang of Academia Sinica who assisted with cryo-electron microscopy. A detailed analysis of the capsid protein structure of the virus was conducted with a resolution of up to 0.25 nanometers, affording the first glimpse of the virus.

The research team found that the Lake Sinai virus has a hollow spherical shell consisting of 240 identical capsid proteins. The inside of the sphere with a diameter of approximately 50 nanometers is for the accommodation of genome RNA. The spheroid is composed of surface spikes, the outer capsid region, and the inner capsid structure. Each surface spike is like a key used to connect and open the door of the honeybee host cell, allowing the viral RNA to invade the host. The outer capsid region is responsible for the assembly and consolidation of the spherical shell, while the inner capsid structure completes the replication and reproduction of the virus by binding to RNA.

The research team also for the first time observed the transition of the virus particle assembly process. In the initial stage of the virus capsid formation, three outer capsid proteins combine to form a stable trimer as the main unit (point), which is then connected to others to form domino-like scaffold structures (lines) of various lengths. The structures are then assembled into a complete shell (surface) like a spherical puzzle. In addition, the research team found that in response to physiological environments of different acidity, the size and structure of the spherical shell changes dynamically, which plays an essential role in the invasion, infection, and replication of the virus in host cells.

The results of this study allow scientists to better understand the transmission route and pathogenic mechanism of the Lake Sinai virus and facilitate the development of new antiviral drugs, such as seeking appropriate natural extracts expected to have antiviral properties based on the virus structures. Antiviral drugs can be mixed with bee feed to prevent infection and improve colony immunity against the virus, thereby effectively preventing pests and diseases. The findings of this study could help to reduce the use of pesticide and to maintain the natural ecological balance, as well as bringing possible solutions to beekeeping’s existing challenges and developing new opportunities to agriculture.