Viruses May Be “Watching” You – Lying in Wait Before Multiplying and Killing

Illustration of Bacteriophages

Phages can sense bacterial DNA damage, which triggers them to replicate and jump ship.

Viruses may be ‘watching’ you – some microbes lie in wait until their hosts unintentionally give them the signal to start multiplying and kill them.

Especially after more than two years of the coronavirus that causes COVID-19, the “mindless killer” moniker is essentially true.

However, there’s more to virus biology than meets the eye.

A suitable illustration is HIV, the virus that causes AIDS. HIV is a retrovirus that does not immediately go on a killing spree when it enters a cell. Instead, it integrates itself into your chromosomes and chills, waiting for the proper opportunity to command the cell to make copies of it and burst out to infect other immune cells and eventually cause AIDS.

Bacteriophages, or simply phages, are naturally occurring viruses that attack and kill bacteria. They cannot infect human cells. Phages are extremely diverse and exist everywhere in the environment, including in our bodies. In fact, humans contain more phages than human cells.

A phage has three main parts: a head, a sheath, and a tail. The phage uses its tail to attach to a bacterial cell. They use the bacteria to replicate themselves. After finding a “matching” bacterial cell, the phage injects its genetic material, hijacking the system normally used for bacterial reproduction. Instead the system will make thousands more phages, which ultimately burst the bacterial cell, releasing it into the environment.

Exactly what moment HIV is waiting for is not clear, as it’s still an area of active study. However, research on other viruses has long indicated that these pathogens can be quite “thoughtful” about killing. Of course, viruses cannot think the way you and I do. But, as it turns out, evolution has bestowed them with some pretty elaborate decision-making mechanisms. For example, some viruses will choose to leave the cell they have been residing in if they detect

For over two decades, my laboratory has been studying the molecular biology of bacteriophages, or phages for short, the viruses that infect bacteria. Recently, my colleagues and I demonstrated that phages can listen for key cellular signals to help them in their decision-making. Even worse, they can use the cell’s own “ears” to do the listening for them.

Escaping DNA damage

If the enemy of your enemy is your friend, 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 a bit like HIV. Upon entering the bacterial cell, lambda decides whether to replicate and kill the cell outright, like most viruses do, or to integrate itself into the cell’s chromosome, as HIV does. If the latter, lambda harmlessly replicates with its host each time the bacteria divides.

This video shows a lambda phage infecting E. coli.

However, like HIV, lambda is not just sitting idle. It uses a special protein called CI like a stethoscope to listen for signs of DNA damage within the bacterial cell. If the bacterium’s DNA gets compromised, that’s bad news for the lambda phage nested within it. Damaged DNA leads straight to evolution’s landfill because it’s useless for the phage that needs it to reproduce. So lambda turns on its replication genes, makes copies of itself, and bursts out of the cell to look for other undamaged cells to infect.

Tapping the cell’s communication system

Instead of gathering intel with their own proteins, some phages tap the infected cell’s very own DNA damage sensor: LexA.

Proteins like CI and LexA are transcription…

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