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Strange virus-like replicators discovered in the human gut

A previously unknown type of replicating agent named "obelisks” has been found in genomic data from stool samples – but we know little about what these entities do
Streptococcus sanguinis bacteria, which live in the mouth, may host replicators named obelisks
UK HEALTH SECURITY AGENCY/SCIENCE PHOTO LIBRARY

A previously unknown type of replicating agent, far smaller and simpler than a virus, has been found in the human gut. These entities have been called “obelisks” by their discoverers.

The obelisks are a “completely new category”, says at the Institute for Sustainable Plant Protection in Bari, Italy, who wasn’t involved in the find. She calls them “a very impressive discovery” that “opens thousands of new questions”.

They were discovered by a team led by at Stanford University in California, who shared the 2006 Nobel prize in physiology or medicine. Because the research hasn’t yet been peer-reviewed, Fire declined to be interviewed.

The obelisks are most similar to another kind of microscopic infectious agent, called viroids. The more familiar viruses, like the one that causes covid-19, are made up of a piece of genetic material like DNA or RNA, surrounded by a protein shell. In contrast, viroids lack this outer layer: each one is just a circular strand of RNA. They are so small, .

Like a viroid, each obelisk is made solely of RNA, which seems to be circular. But there are crucial differences. The RNA of a viroid doesn’t code for any proteins. But the obelisk RNA does. The proteins in question are completely new, bearing no resemblance to any known ones. Fire’s team calls them “oblins”.

Furthermore, the RNA sequence of the obelisks looks like it would fold up into a tight, rod-like shape, rather than staying as a loose circle. The rod-like shape inspired the “obelisk” name.

Fire and his team discovered the obelisks by searching a library of genomic data collected from human stool samples. They had to create a new search tool to scour the data for unfamiliar RNA sequences.

Once they realised the obelisks were there, they searched more datasets. In total, obelisk RNA was detected in 7 per cent of stool samples and 50 per cent of samples from people’s mouths – but these datasets may not be reflective of how common they are worldwide.

“They are not rare,” says Navarro. “And if they are there, they have some role.”

For now, we know little about what the obelisks do. The discovery is solely based on analysing existing genomic data. The next step, says Navarro, is to perform physical experiments to confirm their rod-like structure and start studying their behaviour.

However, Fire and his team found one more clue to the obelisks’ behaviour. They discovered that some laboratory strains of the bacterium Streptococcus sanguinis contained obelisk RNA sequences. The implication is that the obelisks are infecting S. sanguinis. They may be using its cellular machinery to replicate themselves – as viroids do.

S. sanguinis is found in our mouths. It is normally , being associated with good oral health. However, if it gets into the blood, it can cause inflammation of the heart or endocarditis.

Navarro wants to know if the obelisks affect the behaviour of S. sanguinis. “Is the bacteria with this element more virulent? More pathogenic or less pathogenic?” she asks. “It’s an open question.”

It may be that, just as some viruses that infect bacteria can be used to treat bacterial infections, obelisks could one day be used in medicine.

The obelisks are the latest in of , often using , that are expanding our notions of what , viroids and agents can look like. For example, in 2023, a team that included Navarro identified “”: viroid-like objects that seem to infect fungi.

Viruses are often said not to be alive, since they can only replicate inside a host, but it is a contentious issue. The same questions apply to viroids – and potentially to obelisks.

In 2022, Navarro and her colleagues suggested that . Some biologists suspect that the first life was based mostly or solely on RNA. If so, viroids and obelisks could be of this RNA World.

Reference:

bioRxiv

Topics: Viruses