Research

"Viruses largely impact on our agriculture and heath, and even control global-level environmental phenomena. Our group tackles on studying structure-functions of viruses that cause such problems."

1. Exploring Structural Remnants of Icosahedral Viruses in Evolution. "Our challenge lies on exploring functional structural traits of viruses that threaten our health or harm our agriculture using my approach focusing on structure and evolution." The protein folds of the capsid are conserved throughout the lineages of the viruses, demonstrating an evolutionary link among the viruses. Hence, it is critical to clarify what functions are acquired through the evolution of icosahedral capsids by exploring what structural features are common and unique to a specific lineage of the virus. The gain and loss of these structural traits can significantly influence the viability of their essential lifestyles affecting traits such as immune response, cell tropism and virulence. To investigate the acquired structure-functions of the icosahedral viruses, we have focused on studying structure of phyllogenetically closely related pr icosahedral dsRNA and (+)ssRNA viruses. Protozoan/yeast/algal viruses retain ansestoral structural features in unicellular hosts, while they have acquired multifunctionality in their capsid during evolution to ensure their proliferation in multicellular hosts including human. Based on the structural analysis of these viruses, we have hypothesized newly acquired mechanisms with regards to extracellular transmission, genome transcription, and particle assembly/formation of these viruses.

References

  1. Wang et al., Capsid Structure of a Fungal dsRNA Megabirnavirus Reveals Its Previously Unidentified Surface Architecture. PLoS Pathog  (2023)
  2. Munke et al., Primordial Capsid and Spooled ssDNA Genome Structure Unravel Ancestral Events of Eukaryotic Viruses. mBio (2022)
  3. Munke et al., Capsid Structure of a Marine Algal Virus of the Order Picornavirales. J Virol (2020)
  4. Okamoto et al., Acquired functional capsid structures in metazoan totivirus-like dsRNA viruses. Structure (2020)

2. Viral Regulatory Factors on Life-and-Death Dynamics of Algal Blooms. "Our challenge lies on analyzing structure of host-specific algal viruses for revealing how they control harmful algal blooms." Algal blooms greatly impact the marine ecosystem, human activities such as fishery and seaside recreation, and human health. Monitoring of algal blooms is one of the important governmental programs for countries surrounded by the sea, including Sweden. Algal blooms show recurring patterns of sudden appearances and disappearances. A handful of host-specific algal viruses have been isolated from the marine algae that cause harmful algal blooms. The population of these host-specific algal viruses could control the disappearances and the appearances of the algal blooms. Hence, the host-specific algal viruses are key to understanding the life-and-death dynamics of the algal blooms. However, it is still unclear why these viruses are only infectious to certain algae. The capsid structure of these viruses are largely involved in the host-specific infection.Left: An atomic model of host-specific algal virus CtenRANVII. Right: Recurring patterns of seasonal algal blooms. 

References:

  1. Munke et al., Primordial Capsid and Spooled ssDNA Genome Structures Unravel Ancestral Events of Eukaryotic Viruses. mBio (2022)
  2. Wang et al., Structural Insights into Common and Host-Specific Receptor-Binding Mechanisms in Algal Picorna-like Viruses. Viruses (2022)
  3. Munke et al., Capsid structure of a marine algal virus of the order Picornavirales. J Virol (2020)

3. In Vitro and In Situ Intra-particle Genome Transcription in Icosahedral dsRNA Viruses. "Our challenge lies on elucidating dynamical structural and functional changes of icosahedral Viruses in situ." The icosahedral dsRNA viruses are one of the problematic viruses of causing diverse human, animal and crop diseases. To avoid stimulating host innate immune system by their viral dsRNA, these viruses have universal mechanism of synthesizing nascent (+)ssRNA genomes within their virus capsid using the pore and RNA-dependent RNA polymerase (RdRp). We have hypothesized that dynamical structural changes occur in their capsid during the genome synthesis followed by the infection. However, the molecular and structural understanding of its mechanisms are still gravely lacking to date. We have established infectious DNA clone system of the totivirus-like dsRNA virus to be used for biophysical, molecular and cellular functional assays for elucidating a chain of their infection and genome synthesis mechanisms in vitro and in situ.

References: 

  1. Wang et al., A Full-Length Infectious cDNA Clone of a dsRNA Totivirus-like Virus. Virology (2022)

4. Large Microassemblies in Dogma-Breaking Giant Viruses. "Our challenge lies on studying strucure-functions of microassemblies of the giant viruses, which will lead to elucidate their unique mechanisms concerning particle assembly and uncoating, cell entry and genome packaging." Our environment enriches giant amoeba/algal viruses, yet we know little about how they operate. The size of the giant viruses have often reached to the one of bacteria. They are tremendously unique and do not follow long-standing definition and criteria of viruses - witness of the fact that these viruses encode histone-like proteins, and transcriptional factors unlike other viruses. Therefore, they blur a boarderline between viruses and cellular organisms. Interestingly, our previous cryo-EM studies of Melbournevirus and the largest-ever Pithovirus sibericum have discovered mysterious surface and interior microassemblies in their particles. Cryo-EM images of A) Pithovirus sibericum B) Melbournevirus particles 

References

  1. Burton-Smith et al., The 4.4 Å Structure of the Giant Melbournevirus virion belonging to the Marseilleviridae Family. bioRxiv (2022)
  2. Chihara et al., A Novel Capsid Protein Network Allows the Characteristic Inner Membrane Structure of Marseilleviridae Giant Viruses. Sci Rep (2022)
  3. Okamoto et al., Cryo-EM structure of a Marseilleviridae virus particle reveals a large internal microassembly. Virology (2018)
  4. Okamoto et al., Structural variability and complexity of the giant Pithovirus sibericum particle revealed by high-voltage elecron cyro-tomography and energy-filgered electron cyro-microscopy. Sci Rep (2017)

5. Structural Virology Network for Future Pandemics. In the COVID-19 pandemics last three years, we have realized that virus otubreaks are no longer only local problem. Before future pandemics happen, we aim to discover citircal functional structural segments of the so far local pathogenic viruses and determine how they can be used to predict novel therapeutic targets. The network between our group and clinical virologists in Japan (BSL-3/BSL-4 labs in Nagaski University) will be initiated from 2023 having a support of STINT grant. We will initiate a new VR project "Acquired structures of vertebrate flaviviruses and structural designing of non-ADE induced anti-dengue virus antibodies" from 2024 with Takamatsu's group.

Last modified: 2023-11-09
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