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Breakthrough in Understanding Ebola Virus Structure May Enhance Antiviral Development
Currently, there are limited resources available to tackle deadly filoviruses, including Ebola and Marburg viruses. The existing vaccine and antibody treatments are effective against only one type of filovirus, underscoring the urgent need for more comprehensive therapeutic solutions.
Researchers from the La Jolla Institute for Immunology (LJI) are spearheading efforts to develop new antiviral strategies. Through sophisticated imaging techniques, they are delving into the molecular architecture of viruses, identifying potential weak points that could be targeted with innovative therapies.
A recent study published in the journal Cell reveals the first comprehensive images of the Ebola virus nucleocapsid, a crucial structure that could inform the design of antivirals effective against multiple filoviruses. According to Dr. Reika Watanabe, the lead author and staff scientist at LJI, this research represents a significant advancement toward creating a universal antiviral treatment. “The goal is to find a way to halt any viral disease altogether,” she emphasizes.
Examining the Viral Nucleocapsid
The nucleocapsid of the Ebola virus is vital for safeguarding its genetic material and facilitating its replication within host cells, while simultaneously hindering the host’s immune response. This capability allows the virus to convert infected cells into prolific producers of viral particles.
In her pioneering research, Watanabe utilized cryo-electron tomography, allowing her to visualize the nucleocapsid’s structure within infected cells. The nucleocapsid resembles a coiled telephone cord, and through this imaging, Watanabe was able to identify the various stages of its coiling and compression. Notably, she discovered that this cylindrical structure comprises three distinct layers, each serving a unique function during the virus’s replication process. Prior to this investigation, the outer layer’s presence had gone undetected.
Further, Watanabe’s analysis sheds light on how this outer layer is formed, providing a flexible connection between the nucleocapsid and the viral membrane. Dr. Erica Ollmann Saphire, study senior author and LJI’s President and CEO, notes, “We found that the core protein exists in different structural forms across the nucleocapsid’s layers to fulfill varying roles.” Additionally, Watanabe studied how the proteins within these layers interact during assembly and are rearranged when forming new viral particles, further unraveling the complexities of viral infection.
Implications for Targeting Filoviruses
Targeting the nucleocapsid presents a vital opportunity to incapacitate the virus, as Dr. Watanabe indicates: “Without a nucleocapsid, the virus cannot operate. It is central to its function.” Given the evolutionary pressure on filoviruses, she believes the nucleocapsid’s structure has remained largely unchanged, a characteristic termed “conserved” in scientific terminology, signifying its importance across related viral species.
Furthermore, all known pathogenic filoviruses, including both Ebola and Marburg viruses, exhibit this conserved nucleocapsid structure. Watanabe is currently leading research initiatives aimed at understanding the assembly of the nucleocapsid specifically for the Marburg virus, which may open avenues for broader antiviral development.
In addition to Watanabe, contributing authors for the study include Dawid Zyla, Diptiben Parekh, Connor Hong, Ying Jones, Sharon L. Schendel, Willian Wan, and Guillaume Castillon.
More information: Reika Watanabe et al, “Intracellular Ebola Virus nucleocapsid assembly revealed by in situ cryo-electron tomography,” Cell (2024). DOI: 10.1016/j.cell.2024.08.044. www.cell.com/cell/fulltext/S0092-8674(24)00973-5
Provided by: La Jolla Institute for Immunology
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phys.org