Structural Research of Tymoviridae

Tymoviridae is a family of single-stranded positive-sense RNA viruses that infect mainly plants and can cause significant damage to crops worldwide. These viruses induce a wide range of diseases in plants, leading to reduced crop yields, growth retardation, and overall economic losses in the agricultural sector. In recent years, rapid advances in microscopy, especially cryo-electron microscopy (cryo-EM), have provided a platform for structural elucidation of Tymoviridae family members for targeted disease management strategies, such as the development of antiviral drugs or the engineering of resistant crop varieties. Research supports the mitigation of the devastating impact of Tymoviridae on global agriculture.

Progress in Structural Research of Tymoviridae

Significant progress has been made in research on the structure of Tymoviridae, facilitated by cutting-edge techniques such as cryo-EM, X-ray crystallography, and computational modeling. These studies have provided valuable insights into the three-dimensional structure of viruses, elucidating their capsid morphology, protein-protein interactions, and viral genome RNA. Research on the dynamic properties of Tymoviridae capsids, structural determinants of viral replication, and structure-function relationships of viral proteins has deepened the understanding of virus infection mechanisms, paving the way for the development of targeted antiviral strategies, vaccine design, and resistant crop engineering. In addition, researchers have utilized the Citrus Sudden Death Associated Virus (CSDaV) as an expression vector for the rapid production of heterologous proteins, chimeric virus particles, and virus-like particles in plants.

Figure 1. Cryo-EM structure of CSDaV (genus Marafivirus; family Tymoviridae). (Matsumura EE, et al, 2022)

Structural Features of Tymoviridae

Members of this family exhibit the following structural characteristics:

• Viral particles are isometric, unenveloped T=3 icosahedral structures with rounded outlines and prominent surface structures. The capsid protein subunits aggregate in pentamers and hexamers.
• Purified virus particles contain a small amount of RNA (mainly sub-genomic capsid protein mRNA) in a non-infectious protein shell (T) and an infectious nucleoprotein carrying the viral genome (B).
• These viruses possess a positive-sense, single-stranded RNA genome with an unusually high cytidine content (32% to approximately 50%). The genome is capped at its 5' terminus and contains a large open reading frame (ORF) encoding replication-related proteins similar to those found in other members of the "alpha-like" supergroup of single-stranded RNA viruses.

The Significance of Structural Research on Tymoviridae

• Provide insights into the viral assembly process and maturation, understanding the molecular mechanisms involved in viral capsid formation and release of mature viral particles.
• Design immunogens capable of triggering strong and specific immune responses and aid in developing virus-like particle (VLP)-based vaccines.
• Identify potential targets for antiviral interventions and design and develop antiviral drugs that target and destroy critical viral components.
• Identify potential targets for crop-engineered resistance and develop transgenic crops with enhanced resistance to Tymoviridae infection.

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References

1. Matsumura EE, et al. Citrus sudden death-associated virus as a new expression vector for rapid in planta production of heterologous proteins, chimeric virions, and virus-like particles. Biotechnol Rep (Amst). 2022. 35: e00739.
2. Martelli GP, et al. The family Tymoviridae. Arch Virol. 2002. 147(9): 1837-1846.