Discovery of Ushikuvirus A Giant Virus at the Root of Complex Life?

The discovery of ushikuvirus, a newly identified giant DNA virus, adds fresh momentum to the provocative idea that viruses may have helped give rise to the cell nucleus—and played a formative role in the evolution of complex life on Earth.

The origin of life on Earth becomes even more fascinating and complex as we peer into the mysterious world of viruses. Said to have existed since living cells first appeared, these microscopic entities differ greatly from other forms of life. Composed of only genetic material, they lack the ability to synthesize proteins, which are essential for carrying out cellular activity and, ultimately, for life by itself.

As a result, scientists have long sought to unravel virus origins, how they evolve, and how they fit into the conventional tree of life. Professor Masaharu Takemura from the Graduate School of Science, Tokyo University of Science (TUS), Japan, has been at the forefront of this search. In 2001, he, along with Dr. Philip Bell, from the Department of Biological Sciences, Macquarie University, Sydney, independently proposed the cell nuclear virus origin theory, also known as viral eukaryogenesis (term coined by Dr. Bell). According to this hypothesis, the nucleus of eukaryotic cells (cells whose nucleus is bound by a membrane) originated from a large DNA virus such as poxvirus that infected an archaeal ancestor (single-celled microorganisms). Instead of killing the host, the virus set up a long-term presence inside the cytoplasm, and over time acquired essential genes from the host, and became what we now recognize as the nucleus of eukaryotic cells. This suggests that viruses may have played a foundational role in the emergence of life.

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Nowadays, central to this idea are giant viruses that contain DNA, which were found in 2003. When they infect cells, they form specialized structures called virus factories inside the host. Some of these factories are enclosed within a membrane, much like a cell nucleus, where DNA replication takes place, hinting at an evolutionary connection between viruses and complex cells.

In recent years, new types of DNA viruses have been discovered, including members of the family Mamonoviridae, which infect acanthamoeba (a type of amoeba, which is a single-celled microorganism), and the closely related clandestinovirus, which infects vermamoeba (another type of amoeba from a different family).

Now, in a joint study published online in the Journal of Virology on November 24, 2025, Prof. Takemura along with researchers at the National Institute of Natural Sciences (NINS), Japan, report yet another of these giant DNA viruses that infect amoeba. Named ushikuvirus after Lake Ushiku in the Ibaraki Prefecture of Japan, where it was isolated. This discovery offers further support for the nuclear virus origin hypothesis.

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The 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.

Giant viruses are ubiquitously present in the environment. However, their isolation remains a challenge. These viruses are highly diverse and the discovery of ushikuvirus is extremely valuable. The newly discovered ushikuvirus infects vermamoeba, like clandestinovirus, and is morphologically similar to members of the Mamonoviridae family, particularly Medusavirus, a genus characterized by its icosahedral shape and numerous short spikes on the capsid surface. However, ushikuvirus also shows distinct features: it induces a specific cytopathic effect that causes its vermamoeba hosts to grow into unusually large cells, and it possesses multiple spike structures with unique caps on the capsid surface, some with filamentous extensions, not seen in medusaviruses.

Additionally, unlike medusaviruses and clandestinovirus, which replicate within the intact host nucleus, ushikuvirus disrupts the nuclear membrane to produce viral particles. This suggests a phylogenetic link between Mamonoviridae family that utilizes intact nucleus as viral factory and giant viruses like pandoravirus that disrupt the nuclear membrane for replication. Researchers believe that these variations between viruses may have evolved as adaptations to their hosts.

By comparing these structural and functional differences, researchers are beginning to piece together how giant viruses have diversified over time and how their interactions with host cells may have shaped 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.

The discovery of these amoeba-infecting viruses could have practical implications for healthcare. Because certain Acanthamoeba species can cause diseases such as amoebic encephalitis, understanding how giant viruses infect and destroy amoebae may one day help scientists develop new strategies to prevent or treat such infections.

Original Article: A newly isolated giant virus, ushikuvirus, is closely related to clandestinovirus and shows a unique capsid surface structure and host cell interactions; Journal of Virology; DOI:10.1128/jvi.01206-25

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