A virus becomes "sick" when another virus impairs its function. This often involves a battle for control within the host cell. Satellite viruses, such as the recently discovered "MiniFlayer", can attach to other viruses and influence their behavior. Understanding viral interactions, particularly satellite and helper viruses, provides valuable insights into potential antiviral strategies and has wider implications for viral research and treatment.
Author: Ivan Erill, Professor of Biological Sciences, University of Maryland, Baltimore County
Have you ever thought that the virus that gives you a bad cold can also cause you to catch a cold? It might be comforting to know that, yes, viruses do make you sick. Even better, thanks to karma, the culprit turned out to be some other virus.
Viruses, like humans, can become sick from other viruses. The attachment of satellite viruses such as MiniFlayer to other viruses such as MindFlayer demonstrates this phenomenon, providing a potential way for us to gain insight into viral behavior and develop new antiviral therapies.
Viruses become sick because their normal functions are compromised. When a virus enters a cell, it can either lie dormant or start replicating immediately. During the replication process, the virus takes over the cell's molecular factory, makes large copies of itself, and then breaks away from the cell, allowing new copies to grow freely.
Sometimes, however, a virus enters a cell only to discover that its new temporary home is already home to another dormant virus, and what ensues is a battle for control of the cell that either side can win.
But sometimes, when a virus enters a cell, it finds a particularly nasty tenant: another virus waiting to prey on the incoming virus.
I'm a bioinformatician and my lab studies the evolution of viruses. We often encounter "viruses of viruses," but we recently discovered something new: one virus bites the neck of another.
Biologists have known for decades that viruses that prey on other viruses, known as viral "satellites," exist. In 1973, researchers studying bacteriophage P2, a virus that infects E. coli in the gut, discovered that the infection sometimes resulted in the presence of two different types of viruses in cells: phage P2 and phage P4.
Phage P4 can integrate into the chromosome of the host cell and remain dormant. When P2 infects a cell that already carries P4, the latent P4 quickly awakens and uses P2's genetic instructions to create hundreds of its own small virus particles. The unsuspecting P2 is lucky even if it can replicate a few times. In this case, biologists call P2 a "helper" virus because satellite P4 needs P2's genetic material to replicate and spread.
Subsequent research showed that most bacterial species have a diverse set of satellite-assisted systems, such as the P4-P2 system. But viral satellites are not limited to bacteria. In 2003, shortly after the largest known virus, mimivirus, was discovered, scientists also discovered its satellite and named it "Sputnik." Plant virus satellites, which lie dormant in plant cells waiting for other viruses, are also common and may have important consequences for crops.
Although researchers have discovered satellite-assisted virus systems in nearly all areas of life, their importance to biology remains underappreciated. Most obviously, virus satellites have a direct impact on their "helper" viruses, often disabling them but sometimes making them more effective killers. However, this is probably their smallest contribution to biology.
Satellites and their "helpers" are still engaged in an endless evolutionary arms race. Satellites evolved new ways to exploit the assistants, and the assistants evolved countermeasures to thwart the satellites. Since both sides are viruses, the outcome of this civil war must include something of interest: antiviral drugs.
Recent research suggests that many antiviral systems thought to have evolved in bacteria, such as the CRISPR-Cas9 molecular scissors used in gene editing, may have originated from bacteriophages and their satellites. Somewhat ironically, helper viruses and their satellite viruses have high rates of turnover and mutation, making them an evolutionary hotspot for antiviral weapons. To defeat each other, satellite viruses and helper viruses present an unparalleled array of antiviral systems for researchers to exploit.
Viral satellites have the potential to change researchers' understanding of strategies to fight viruses, but there is still much to be done to understand them. In our recent work, my collaborators and I describe a satellite phage that is completely different from previously known satellites and that has evolved a unique and bizarre way of life.
Phage hunters at the University of Maryland, Baltimore County, isolated a satellite phage called MiniFlayer from the soil bacterium Streptomyces scabies. The study found that MiniFlayer is closely related to a helper virus called phage MindFlayer, which infects Streptomyces scabies. However, further research revealed that MiniFlayer is not an ordinary satellite virus.
MiniFlayer is the first known satellite phage to lose its ability to hibernate. The inability to wait for helpers to enter cells is an important challenge for satellite phages. If you need another virus to replicate, how do you ensure it gets into the cell at the same time you're replicating?
Miniphages rise to this challenge with evolutionary grit and horror-movie inventiveness. MiniFlayer did not sit back and wait, but took the initiative. Taking cues from Dracula and Alien, the satellite phage has evolved a short appendage that can bite its helper's neck like a vampire. Together, the unsuspecting helper and its passengers seek out a new host, where the viral drama will play out again. We still don't know how the "Mini Killer" subdued its assistant, nor whether the "Psych Killer" has evolved countermeasures.
If the recent pandemic has taught us anything, it’s that our supply of antiviral drugs is quite limited. Studying the complex, intertwined and sometimes predatory nature of viruses and their satellite viruses (such as the ability of "mini-killers" to latch on to the necks of their assistants) has the potential to open new avenues for antiviral treatments.