In work published online on November 24, 2025, in the Journal of Virology, the team reports the discovery of ushikuvirus, a newly isolated giant virus named after Lake Ushiku in Ibaraki Prefecture, where it was found. Ushikuvirus infects vermamoeba and belongs to a group of large DNA viruses related to the family Mamonoviridae, adding another data point to studies of viral roles in early eukaryotic evolution.
Study leader Professor Masaharu Takemura of the Graduate School of Science at Tokyo University of Science has long explored the idea that viruses helped give rise to eukaryotic cells. In 2001, he and Dr. Philip Bell of Macquarie University independently developed the cell nuclear virus origin theory, also known as viral eukaryogenesis, which proposes that the nuclei of eukaryotic cells originated from a large DNA virus similar to a poxvirus that infected an archaeal ancestor and established a persistent presence inside the cytoplasm. Over time, this virus is hypothesized to have acquired host genes and evolved into the membrane-bound nucleus characteristic of eukaryotic cells, implying that viruses could have played a foundational role in the emergence of complex cellular life.
A central focus of this hypothesis today is the study of giant DNA viruses, first identified in 2003, which form large intracellular virus factories during infection. In some cases these factories are enclosed by membranes and serve as sites for viral DNA replication, resembling cell nuclei and suggesting an evolutionary connection between giant viruses and eukaryotic cellular compartments.
Researchers have recently described several new DNA viruses within this broader group, including members of the family Mamonoviridae that infect acanthamoeba and the related clandestinovirus that infects vermamoeba. Ushikuvirus expands this set of known viruses infecting free-living amoebae and helps clarify relationships within the giant virus lineages that interact with these hosts.
The study team included Master's degree students Jiwan Bae and Narumi Hantori at Tokyo University of Science, together with Dr. Raymond Burton-Smith and Professor Kazuyoshi Murata at the National Institute of Natural Sciences. "Giant viruses can be said to be a treasure trove whose world has yet to be fully understood. One of the future possibilities of this research is to provide humanity with a new view that connects the world of living organisms with the world of viruses," says Prof. Takemura.
Giant viruses are widespread in natural environments but remain difficult to isolate because of their diversity and complex host relationships. The researchers describe ushikuvirus as morphologically similar to Mamonoviridae members such as Medusavirus, with an icosahedral capsid and numerous short spikes on its surface, but note that it also exhibits distinct structural and biological traits.
In particular, ushikuvirus infection of vermamoeba produces a specific cytopathic effect in which the host cells grow into unusually large cells. The virus carries multiple spike structures on the capsid surface that have unique caps and, in some cases, filamentous extensions not observed in medusaviruses, marking it as structurally distinct within this group.
Ushikuvirus also differs in how it uses the host nucleus during replication. Whereas medusaviruses and clandestinovirus replicate within an intact host nucleus, ushikuvirus disrupts the nuclear membrane to generate viral particles, a strategy that aligns it with giant viruses such as pandoravirus that break down nuclear boundaries during replication.
According to the authors, these contrasting replication modes suggest a phylogenetic link between Mamonoviridae viruses that rely on an intact nucleus as a viral factory and giant viruses that disrupt the nuclear membrane. They propose that such differences reflect evolutionary adaptations to particular host cell environments and that comparing them can help reconstruct how virus-host interactions have diversified over time.
By systematically examining structural features and infection strategies across these viruses, researchers are assembling a more detailed picture of how giant viruses evolved and how they may have influenced the development of complex eukaryotic cells. "The discovery of a new Mamonoviridae-related virus, 'ushikuvirus,' which has a different host, is expected to increase knowledge and stimulate discussion regarding the evolution and phylogeny of the Mamonoviridae family. As a result, it is believed that we will be able to get closer to the mysteries of the evolution of eukaryotic organisms and the mysteries of giant viruses," says Prof. Takemura.
The work also highlights potential medical relevance because some Acanthamoeba species can cause serious conditions such as amoebic encephalitis. A better understanding of how giant viruses infect and destroy amoebae could eventually inform strategies to prevent or manage diseases involving these protist pathogens.
Research Report: A newly isolated giant virus, ushikuvirus, is closely related to clandestinovirus and shows a unique capsid surface structure and host cell interactions
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