Viruses can “watch” you – some microbes wait until their hosts unknowingly give them the signal to start multiplying and kill them | Kiowa County Press


Phages can detect bacterial DNA damage, causing them to replicate and jump ship. Design Cells/iStock via Getty Images Plus

Ivan Erill, University of Maryland, Baltimore County

After more than two years of the COVID-19 pandemic, you might imagine a virus as an evil spiked bullet – a mindless killer that enters a cell and hijacks its machinery to create a million copies of itself before bursting. . For many viruses, including the coronavirus that causes COVID-19, the epithet “blind killer” is essentially true.

But there’s more to the biology of viruses than meets the eye.

Take HIV, the virus that causes AIDS. HIV is a retrovirus that does not go straight into a killing spree when it enters a cell. Instead, it embeds itself in your chromosomes and shivers, waiting for the right moment to command the cell to make copies of it and burst out to infect other immune cells and eventually cause AIDS.

The exact timing that HIV is waiting for is still an active area of ​​study. But research on other viruses has long suggested that these pathogens can be quite “thoughtful” to kill. Of course, viruses can’t think like you and me. But, it turns out that evolution has endowed them with quite elaborate decision-making mechanisms. Some viruses, for example, will choose to leave the cell they were residing in if they detect DNA damage. Even viruses, it seems, don’t like to stay in a sinking ship.

My lab has been studying the molecular biology of bacteriophages, or phages for short, the viruses that infect bacteria, for over two decades. Recently, my colleagues and I showed that phages can listen to key cellular signals to help them in their decision making. Worse still, they can use the cell’s own “ears” to listen for them.

Escape DNA damage

If the enemy of your enemy is your friend, the phages are certainly your friends. Phages control bacterial populations in nature and clinicians are increasingly using them to treat bacterial infections that do not respond to antibiotics.

The best-studied phage, lambda, works much like HIV. Upon entering the bacterial cell, lambda decides to replicate and kill the cell, as most viruses do, or integrate into the cell’s chromosome, as HIV does. In the latter case, lambda harmlessly replicates with its host each time the bacterium divides.

This video shows an infecting lambda phage E.coli.

But, like HIV, lambda doesn’t just sit idle. It uses a special protein called CI like a stethoscope to listen for signs of DNA damage in the bacterial cell. If the bacteria’s DNA is compromised, that’s bad news for the lambda phage nested there. Damaged DNA leads directly to the discharge of evolution because it is useless for the phage which needs it to reproduce. Thus, lambda turns on its replication genes, copies itself, and exits the cell to search for other undamaged cells to infect.

Operate the cell communication system

Some phages, instead of collecting information with their own proteins, exploit the infected cell’s own DNA damage sensor: LexA.

Proteins like CI and LexA are transcription factors that turn genes on and off by binding to specific genetic templates in the DNA instruction book that is the chromosome. Some phages like Coliphage 186 have figured out that they don’t need their own viral CI protein if they have a short DNA sequence in their chromosomes that bacterial LexA can bind to. Upon detecting DNA damage, LexA will activate the phage’s replication and killing genes, essentially crossing the cell by killing itself while allowing the phage to escape.

Scientists first reported the role of CI in phage decision making in the 1980s and the counterintelligence trick of Coliphage 186 in the late 1990s. Since then there have been a few more reports of phages exploiting bacterial communication systems. An example is the phage phi29, which exploits its host’s transcription factor to detect when the bacterium is about to generate a spore, or a kind of bacterial egg capable of surviving extreme environments. Phi29 instructs the cell to package its DNA into the spore, killing budding bacteria once the spore has germinated.

Transcription factors turn genes on and off.

In our recently published research, my colleagues and I show that several groups of phages have independently evolved the ability to tap into another bacterial communication system: the CtrA protein. CtrA integrates multiple internal and external signals to trigger different developmental processes in bacteria. Among these, the production of bacterial appendages called flagella and pili is essential. It turns out that these phages attach themselves to the pili and flagella of bacteria in order to infect them.

Our main hypothesis is that phages use CtrA to estimate when there will be enough bacteria nearby bearing pili and flagella that they can easily infect. A pretty clever trick for a “dumb killer”.

They aren’t the only phages that make elaborate decisions – all without even having a brain. Some phages that infect Bacillus bacteria produce a small molecule each time they infect a cell. Phages can detect this molecule and use it to count the number of phage infections that occur around them. Like alien invaders, this count helps decide when they should turn on their replication and kill genes, killing only when hosts are relatively abundant. In this way, the phages ensure that they never run out of hosts to infect and guarantee their own long-term survival.

Countering Viral Counterintelligence

You might be wondering why you should care about counterintelligence operations run by bacterial viruses. Although bacteria are very different from humans, the viruses that infect them are not that different from the viruses that infect humans. Virtually all of the tricks played by phages were later found to be used by human viruses. If a phage can exploit bacterial lines of communication, why wouldn’t a human virus exploit yours?

So far, researchers don’t know what human viruses might be listening to if they hijack these lines, but many options come to mind. I think that, like phages, human viruses could potentially be able to count their numbers to strategize, detect cell growth and tissue formation, and even monitor immune responses. For now, these possibilities are just speculation, but scientific research is ongoing.

Having viruses eavesdropping on your private cell conversations isn’t the prettiest of pictures, but it’s not without a silver lining. As intelligence agencies around the world are well aware, counterintelligence only works when it’s covert. Once detected, the system can very easily be exploited to provide false information to your enemy. Likewise, I think future antiviral therapies could combine conventional artillery, like antivirals that prevent viral replication, with information warfare trickery, like tricking the virus into believing that the cell it’s in belongs to a different fabric.

But, hush, don’t tell anyone. Viruses could be listening!

The conversation

Ivan Erill, Associate Professor of Biological Sciences, University of Maryland, Baltimore County

This article is republished from The Conversation under a Creative Commons license. Read the original article.


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