Viruses Can Latch Onto One Another

Accidental discovery of virus attaching to another virus

At the University of Maryland Baltimore County (UMBC), a program called SEA-PHAGES requires students to isolate bacteriophages, send them off for sequencing and utilize various tools to analyze the results.

One semester, a sample sent to the University of Pittsburgh was flagged as contaminated. It contained two sequences: a large one that belonged to a phage and a small sequence that didn’t map to anything that the researchers knew. This was unexpected, and quite odd.

Dr. Tagide deCarvalho, assistant director of the College of Natural and Mathematical Sciences core facilities at UMBC, was asked to use a transmission electron microscope (TEM) to visualize what was going on in the sample. “Not everyone has a TEM at their disposal,” deCarvalho explains. “I’m able to follow up on some of these observations and validate them with imaging. There’s elements of discovery we can only make using the TEM.”

And quite the discovery it was. The researchers had captured one virus latching onto another – something that had never been seen before. They share their unexpected finding in the Journal of the International Society of Microbial Ecology.

“When I saw it, I was like, ‘I can’t believe this',” deCarvalho says. “No one has ever seen a bacteriophage – or any other virus – attach to another virus.”

MindFlayer offers MiniFlayer support 

Some viruses, called “satellites”, cannot complete their life cycle without a helping hand. They depend on their host and another virus, aptly called a “helper” virus.

The helper virus either assists in building the satellite’s protective shell, builds its capsid or supports the process of DNA replication. It was known that for this to happen, both viruses need to be close together – at least temporarily. But the idea that the satellite could physically attach itself to the helper? That was unheard of.

The students that isolated the satellite virus decided to name it “MiniFlayer”, and its helper “MindFlayer”.

Co-evolution of satellite and helper viruses over millions of years

To further understand this viral relationship, UMBC graduate student Elia Mascolo was tasked with analyzing the genomes of the Miniflayer, Mindflayer and the host organism.

In order for satellite viruses to reproduce when a helper virus comes to hand, most species contain a specific gene that allows them to integrate into their host’s genetic material. When the host cell divides, it also copies the satellite virus’ DNA alongside its own.

MiniFlayer is the first known instance of a satellite virus not possessing this gene. That means its host’s DNA is completely inaccessible – unless MindFlayer is there to offer support. “Attaching now made total sense,” Dr. Ivan Erill, professor of biological sciences at UMBC, explains. “Because otherwise, how are you going to guarantee that you are going to enter into the cell at the same time?”

Bioinformatics analyses demonstratd that MindFlayer and MiniFlayer have been co-evolving for a long period of time. “This satellite has been tuning in and optimizing its genome to be associated with the helper for, I would say, at least 100 million years,” Erill concludes. The team suggest that there may be more instances of viruses latching on to one another, just waiting to be discovered.

Reference: deCarvalho T, Mascolo E, Caruso SM, et al. Simultaneous entry as an adaptation to virulence in a novel satellite-helper system infecting Streptomyces species. ISME J. 2023. doi: 10.1038/s41396-023-01548-0

This article is a rework of a press release issued by the University of Maryland Baltimore County. Material has been edited for length and content.