For a quarter century, a small laboratory at Portland State University has been asking a question that humanity has not yet answered: where viruses come from, and how they change over time. A three-year, million-dollar grant from the National Science Foundation now lets that inquiry turn toward cruciviruses, strange hybrid agents that seem to carry traits of both RNA and DNA viruses, a boundary once believed to be firm. Found in places as remote as Antarctic lake water and as ordinary as a campus lawn, they remain largely a mystery, their hosts unseen. What is being sought is not only knowledg
Portland State Lab Wins $1 Million NSF Grant to Study How RNA and DNA Viruses Interact
A combination between the two would be really scary
Mark
Why do cruciviruses matter so much to people outside virology?
Mimi
Because they challenge an assumption. RNA and DNA viruses were thought to have separate origins, and cruciviruses look like a product of the two combining.
Mark
Where have they been found?
Mimi
In environmental samples, from Antarctic lake water to soil on the Portland State campus. Hundreds have been identified since the lab's 2012 report.
Luke
But they've only got sequences, right? No actual particles?
Mimi
Correct. Nacho de la Higuera says that's a major limitation, and the sequences differ so much from each other that a lot is still unclear.
Mark
And the hosts?
Mimi
Unknown. The team suspects eukaryotic microbes, single-celled organisms with a nucleus, but that's a suspicion, not a finding.
Luke
Then the pandemic angle should be read carefully. Stedman says understanding this might help us think about new pandemics, but nothing reported shows a hybrid threat to humans.
Mimi
Right. He frames it as studying the process in a non-medical context first, then asking whether it's likely elsewhere.
Mark
What about the capsid work?
Mimi
A former high school intern built an AI tool that tells RNA virus capsids from crucivirus ones. De la Higuera says it could help design better gene therapy and vaccine delivery tools.
Luke
That's a potential application, not a result. The article doesn't report any such tool yet.
O Pulso
- A boundary that scientists long assumed was fixed now appears porous, as hybrid viruses blur the line between RNA and DNA lineages.
- Hundreds of cruciviruses have turned up in samples ranging from Antarctic lakes to campus soil, yet no one knows what they infect.
- The team is racing to locate suspected single-celled eukaryotic hosts and to catch a transfer event between viruses in the act.
- Machine learning models are being built to trace the evolutionary history of these viruses, with findings already suggesting new ways to package genetic material for vaccines and gene therapies.
For a quarter century, a small laboratory at Portland State University has been asking a question that humanity has not yet answered: where viruses come from, and how they change over time. A three-year, million-dollar grant from the National Science Foundation now lets that inquiry turn toward cruciviruses, strange hybrid agents that seem to carry traits of both RNA and DNA viruses, a boundary once believed to be firm. Found in places as remote as Antarctic lake water and as ordinary as a campus lawn, they remain largely a mystery, their hosts unseen. What is being sought is not only knowledge of the living world's oldest exchanges, but an early understanding of how such crossings might one day matter to human health.
For the past 25 years, biology professor Ken Stedman's eXtreme Virus Lab at Portland State University has pursued a stubborn question: where viruses came from and how they evolve. Now a three-year, $1 million National Science Foundation grant will carry that search further.
The focus is a group of viruses called cruciviruses. Scientists long believed DNA viruses like monkeypox and RNA viruses like influenza arose entirely apart. In 2012, Stedman's lab published the first findings on cruciviruses, which seem to have emerged from an unusual recombination between the two. Since then, hundreds have been identified, from Antarctic lake water to soil on the PSU campus. The deeper the lab looks, the more intertwined the story becomes.
The team wants to understand how often these viruses swap genetic material and whether such an exchange can be caught as it happens. Stedman links the work to pandemic preparedness, noting that a combined RNA and DNA virus would be alarming, so understanding how it arises in a non-medical setting is essential. Research associate Ignacio "Nacho" de la Higuera points out a central limit: the lab has only genetic sequences, not physical viral particles, and the hosts remain unidentified. Researchers are developing methods to find the suspected single-celled hosts in environments where cruciviruses are known.
Alongside evolutionary trees, the lab is using machine learning, including an algorithm developed by a former high school intern that distinguishes capsids of RNA and cruciviruses. Cruciviruses are the only known example of a capsid able to enclose both RNA and DNA genomes, a finding that could eventually improve tools for gene therapy and vaccines.
The project will involve students at several levels, along with outreach to museums and rural communities, and a planned undergraduate course. The milestones to watch are whether the hosts are found and whether a transfer between RNA and DNA viruses is caught.
For the past 25 years, biology professor Ken Stedman's eXtreme Virus Lab at Portland State University has chased a question that remains largely unanswered: where viruses came from and how they evolve. The lab has now been awarded a three-year, $1 million grant from the National Science Foundation to push that work further.
The grant centers on a group of viruses called cruciviruses. For a long time, DNA viruses such as monkeypox and RNA viruses such as the flu were thought to have evolved entirely separately. In 2012, Stedman's lab was the first to publish findings on cruciviruses, which appear to have arisen through an unprecedented recombination between RNA and DNA viruses. Since then, hundreds have been identified in environmental samples, from Antarctic lake water to soil on the PSU campus. The lab is one of the few, if not the only one, in the world dedicated to studying them.
Stedman says the deeper the lab looked, the more tangled the picture became. Researchers had assumed RNA and DNA viruses had wholly different origins, but cruciviruses offer evidence that the two groups interact. The new project is a targeted discovery effort aimed at cruciviruses, related RNA viruses and the elusive microorganisms that host them. By assessing patterns of horizontal gene transfer, the team wants to learn how often this back-and-forth between viruses happens, and whether it can be caught in the act.
Stedman ties the work to pandemic preparedness. A combination of an RNA and a DNA virus would be, in his words, really scary, so the lab wants to understand how it happens in a non-medical setting and then consider whether something similar could occur in a way that matters for human health.
One of the biggest limits, according to research associate Ignacio "Nacho" de la Higuera, who joined the lab as a postdoctoral researcher in 2016, is that the team has only genetic sequences, not physical viral particles. The sequences are so different from one another that much remains unknown. The team plans to study DNA viruses, cruciviruses and related RNA viruses within the same sample, looking for evidence of a recent transfer event.
The researchers also do not know what cruciviruses infect. They are developing techniques to go to an environment with known cruciviruses and find the host cells, which they suspect are eukaryotic microbes, single-celled organisms with a nucleus. Stedman notes that identifying a host would let them observe what a virus does inside it and learn far more about how it works.
The analysis will combine evolutionary trees built from the sequences with newer machine learning algorithms that model the evolutionary history of cruciviruses. A former high school intern in the lab developed an AI algorithm that distinguishes the capsids, the protein shells enclosing a virus's genetic material, of RNA viruses from those of cruciviruses. De la Higuera says cruciviruses are the only known example of a capsid protein that can enclose both RNA and DNA viral genomes. The machine learning work has shown that nature has shaped capsids in different ways to package DNA or RNA. Because capsids are used in biomedicine to deliver gene therapy and vaccines, he says the findings could eventually help design better tools for packaging either type of genome.
The grant will involve high school, undergraduate and graduate researchers. The lab regularly collaborates with the Oregon Museum of Science and Industry and plans to expand outreach on virus evolution to rural communities through virtual programs. De la Higuera is also developing a course-based undergraduate research experience to bring the work into more classrooms. The next milestones to watch are whether the team can find the hosts and catch a transfer event between RNA and DNA viruses.
Citações Notáveis
Having a host means you can then look at the virus and what the virus is doing inside the host, and actually start to learn a lot more about how it's working.— Ken Stedman, Professor, Portland State University
Cruciviruses present the only known example of a capsid protein that can enclose both RNA and DNA viral genomes.— Ignacio de la Higuera, research associate (paraphrased)
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