The story of how life began on Earth grows even more intriguing when viruses enter the picture. These microscopic particles are thought to have existed since the earliest cells emerged. Unlike living cells, viruses consist only of genetic material and cannot produce proteins on their own. Because proteins are essential for cellular activity and survival, viruses depend entirely on host cells to function.
For decades, scientists have tried to understand where viruses came from, how they evolved, and how they fit into the tree of life. Professor Masaharu Takemura of the Graduate School of Science at Tokyo University of Science (TUS), Japan, has been a leading figure in this effort. In 2001, he and Dr. Philip Bell of the Department of Biological Sciences at Macquarie University, Sydney, independently proposed the cell nuclear virus origin theory, also known as viral eukaryogenesis (term coined by Dr. Bell).
This hypothesis suggests that the nucleus of eukaryotic cells (cells whose nucleus is bound by a membrane) may have originated from a large DNA virus such as poxvirus that infected an archaeal ancestor (single-celled microorganisms). Rather than destroying its host, the virus may have established a stable presence in the cytoplasm. Over time, it likely absorbed important genes from the host cell and gradually transformed into what we now recognize as the nucleus of eukaryotic cells. If correct, this theory means viruses may have played a central role in the rise of complex life.
Giant DNA Viruses and Virus Factories
Support for this idea grew in 2003 with the discovery of giant DNA viruses. When these viruses infect cells, they create structures known as virus factories inside their hosts. In some cases, these factories are surrounded by membranes and serve as sites for DNA replication, resembling a primitive version of a cell nucleus. This similarity has strengthened the proposed evolutionary link between viruses and complex cells.
In recent years, researchers have identified additional giant DNA viruses. Among them are members of the Mamonoviridae family, which infect acanthamoeba (a type of amoeba, which is a single-celled microorganism), and clandestinovirus, a closely related virus that infects vermamoeba (another type of amoeba from a different family).
Discovery of Ushikuvirus
In a new study published in the Journal of Virology, Prof. Takemura and collaborators at the National Institute of Natural Sciences (NINS), Japan, describe another giant DNA virus that infects amoeba. The virus, named ushikuvirus after Lake Ushiku in Ibaraki Prefecture, Japan, where it was isolated, adds further evidence supporting the nuclear virus origin hypothesis.
The research team included Mr. Jiwan Bae and Mrs. Narumi Hantori, Master’s degree students at the Graduate School of Science, TUS, along with Dr. Raymond Burton-Smith and Professor Kazuyoshi Murata from NINS.
“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.
Unique Structure and Infection Strategy
Giant viruses are widespread in nature, but isolating them is difficult. They are also remarkably diverse, making each new discovery significant. Ushikuvirus infects vermamoeba, similar to clandestinovirus, and shares structural similarities with the Mamonoviridae family, particularly Medusavirus. Medusavirus is known for its icosahedral shape and numerous short spikes covering its capsid surface.
However, ushikuvirus also displays important differences. It triggers a distinct cytopathic effect that causes infected vermamoeba cells to grow unusually large. Its capsid surface contains multiple spike structures topped with unique caps, some with filament-like extensions not seen in medusaviruses.
Another key difference lies in how the virus replicates. Medusaviruses and clandestinovirus reproduce within an intact host nucleus. In contrast, ushikuvirus breaks down the nuclear membrane during replication to produce new viral particles. This behavior suggests a possible evolutionary connection between Mamonoviridae family viruses that use the intact nucleus as a viral factory and giant viruses such as pandoravirus that disrupt the nuclear membrane. Scientists believe these differences may reflect adaptations to different hosts over time.
Clues to Eukaryotic Evolution
By examining these structural and functional variations, researchers are gaining insight into how giant viruses diversified and how their interactions with host cells may have influenced the evolution of complex eukaryotic life.
“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.
Potential Healthcare Implications
The discovery of amoeba-infecting giant viruses may also have practical value. Certain Acanthamoeba species can cause serious illnesses, including amoebic encephalitis. A deeper understanding of how giant viruses infect and destroy amoebae could eventually help researchers develop new approaches to preventing or treating these infections.
Dr. Masaharu Takemura is a Professor in the Department of Mathematics and Science Education, Graduate School of Science at the Tokyo University of Science, Japan. His research focuses on giant virus biology, viral eukaryogenesis, and virus education. He has published more than 120 scientific papers and has received over 2,500 citations. His long-term goal is to clarify how giant viruses and eukaryotes evolved and to create educational materials that improve virus literacy.
This research was supported by JSPS/KAKENHI grant number 20H03078 and Joint Research of the Exploratory Research Center on Life and Living Systems (ExCELLS) (ExCELLS program No, 22EXC601-4).
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