Scientists don’t know what they see when two viruses suddenly start ‘hugging’ under their microscope

For the first time, scientists have witnessed something they never thought could happen: a virus clinging to another virus.

Somewhat accidentally, scientists have discovered that some viruses cling to other viruses to survive. This can be read in the magazine The ISME Journal. “When I saw it, I couldn’t believe it,” says researcher Tagide deCarvalho. “No one has ever seen a bacteriophage – or any other virus for that matter – attach itself to another virus.”

Scientists weren’t looking for ‘cuddling viruses’ at all, but discovered them more or less by accident. It all started when students from the University of Maryland had to work on bacteriophages for a school assignment: viruses that can kill bacteria. The students had to isolate a bacteriophage and have it sequenced, and then further analyze the DNA sequence obtained. So far nothing special. But that changed when, during the sequencing of one of the bacteriophages, not only the genetic material of the bacteriophage turned up, but also that of an unknown organism. It suggested that the isolation of the bacteriophage had not gone completely well. University teachers then made a second attempt to isolate the bacteriophage. But that produced the same result, namely genetic material that hinted at the presence of two organisms.

The teachers then called in deCarvalho, who had access to a transmission electron microscope (TEM for short) and was therefore in the perfect position to determine exactly what was going on. DeCarvalho unleashed the microscope on the apparently isolated bacteriophage and was astonished to discover not one, but two bacteriophages clinging to each other.

Helping hand
It has been known for some time that some viruses need other viruses in addition to a host in order to reproduce. These viruses are also called satellite viruses, while their companions are referred to as ‘helpers’. For example, these helpers can help a satellite virus copy its DNA or create a protein coat (which encloses and protects the virus’s genetic material). It was assumed that this cooperation was quite distant in nature and only required that the satellite virus and the helper be (at least temporarily) in each other’s proximity (see box).

Remote help
Satellite viruses and helpers are not new to scientists. In 1973, a bacteriophage was discovered that needs help with its multiplication. This involved the bacteriophage P4 that infects the well-known bacterium E. coli. P4 typically has a lysogenic lifestyle, meaning it invades its host’s genome in order to reproduce. Now P4 is perfectly capable of invading the chromosome of its host on its own. But what it fails to do is multiply itself. P4 needs help for this, namely from a bacteriophage that researchers refer to as P2. How exactly does that work? Well, a lot less spectacular than you might think. P4 invades its host’s chromosome and simply waits for P2 to arrive. Once P2 invades a cell where P4 is already hanging out, P4 springs into action and uses the genetic instructions from P2 – the ‘helper’ – to multiply.

It may have been known for decades that some viruses need to cooperate, but there was no evidence that they really had to cling to each other for successful cooperation. Until now. Because deCarvalho really saw with the help of the transmission electron microscope that a satellite virus had clung to its helper.

Necessary cooperation
A closer analysis of the genomes of the satellite, helper and host (a Streptomycesbacteria) provides more insight into the necessity of this ‘hug’. For example, scientists discovered that the satellite virus – unlike the P4 mentioned above – cannot wait quietly in the DNA of its host for help. The virus is not able to enter the genome of its host on its own; he needs a helper for that. And that’s quite problematic because it means that every time this virus enters a host, it actually has to be in the presence of that helper in order to enter the host’s genome and replicate. “Clinging then makes perfect sense,” says researcher Ivan Erill. “Because how else will the satellite virus ensure that it enters the cell at exactly the same time (as the helper, ed.)?”

In purple the satellite virus clinging to the larger helper virus. Image: Tagide deCarvalho.

And so that’s what this satellite virus does; With a short tail – which he may have developed especially for this collaboration – he clings to the neck of the much larger helper virus (see also the image above).

Traces of an embrace
And when researchers looked more closely for these close hugs, they soon discovered that they occur frequently. Of the 50 helpers they detected in additional samples, 40 had the satellite virus hanging around their necks. And of the remaining 10 helpers who did not seem helpful, many turned out to have been helpful in the past, because researchers discovered traces of a hug in their ‘neck’, in the form of tail fibers, from satellite viruses.

The special collaboration between these two viruses not only seems to be quite common. This is most likely also very old, the scientists say. Research strongly indicates that the satellite virus and its helper have been co-evolving for a long time – at least 100 million years – or adapting to each other through evolution. And the researchers suspect that these are far from the only viruses that conclude their collaboration with a ‘hug’; it is expected that many more of these types of close collaborations are waiting to be discovered.

It is easy to explain why scientists have an above-average interest in collaborations between satellite viruses and helpers. After all, most helpers and satellite viruses are involved in a kind of arms race, where helpers evolve to counter exploitation by satellite viruses and satellite viruses are forced to respond with new ways to (continue to) use helpers. And this ongoing battle between viruses is interesting, Erill explains, because it can lead us to new ways to fight viruses. Because although we (fortunately) have nothing to fear from bacteriophages, there are of course many other viruses that can be dangerous to people. And by looking at how viruses cross swords, we may also be able to discover ways in which we can fend off viruses. It is currently unclear whether the ‘hugging’ viruses that researchers have now discovered are also involved in such an arms race; For example, scientists do not yet know exactly how the satellite virus forces help and whether the helper has mechanisms to shake off such an apparently nasty satellite virus. Follow-up research should reveal this.