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

Some microorganisms wait until their hosts unwittingly give them the signal to begin growing and killing them before viruses start to "watch" them and attack them.                                                                                                                      

Many people imagine a virus as a horrible spiky ball, essentially a mindless killer that enters a cell and commandeers its machinery to generate a billion copies of itself before bursting out, especially after more than two years of the COVID-19 pandemic. The term "mindless killer" is fundamentally accurate for numerous viruses, including the coronavirus that causes COVID-19.

HIV, the virus that causes AIDS, serves as an appropriate example. Being a retrovirus, HIV doesn't instantly start destroying cells when it enters one. Instead, it merges with your chromosomes and waits for the right moment to tell the cell to generate copies of it and release them, infecting other immune cells and ultimately leading to AIDS.

Bacteriophages, often known as phages, are viruses that naturally attack and eradicate bacteria. Human cell infection is impossible. Phages come in a wide variety and are present in many parts of the environment, including human bodies. Humans actually have more phages than human cells.

The head, sheath, and tail are the three primary components of a phage. The phage affixes to a bacterial cell using its tail. They reproduce themselves by using the bacteria. The phage injects its genetic material into a "matching" bacterial cell after identifying one, taking over the method typically employed for bacterial reproduction. Instead, countless more phages will be produced by the system, which will eventually burst the bacterial cell and release it into the environment.        

Since this is currently a topic of active research, it is unclear exactly what moment HIV is waiting for. However, studies on other viruses have long suggested that these infections are capable of killing extremely "thoughtfully." Of course, viruses are unable to think in the same ways as people. But it turns out that evolution has given them some rather complex decision-making abilities. For instance, if they notice DNA damage, some viruses will decide to leave the cell they have been living in. It seems that not even viruses like to stay on a ship that is sinking.

My group has been researching the molecular biology of bacteriophages, or phages for short, the viruses that infect bacteria, for more than 20 years. My coworkers and I recently showed that phages can listen for important cellular signals to aid them in making decisions. Even worse, they are able to use the cell's built-in "ears" to conduct the listening on their behalf.

Phages are unquestionably your friends if the adversary of your enemy is also your buddy. In the natural world, phages regulate bacterial populations, and doctors are utilizing them more frequently to treat bacterial infections that do not respond to antibiotics.

Lambda, the most well-studied phage, functions somewhat like HIV. Lambda chooses when it enters the bacterial cell whether to multiply and completely destroy the cell, as most viruses do, or to integrate itself into the chromosome, like HIV does. If the latter, each time the bacteria divide, lambda replicates without harming its host.

Similar to HIV, lambda is not dormant, though. It listens for indications of DNA damage inside the bacterial cell using a particular protein called CI, which is analogous to a stethoscope. The lambda phage that is nested inside the bacterium risks having its DNA compromised. For the phage that needs it to reproduce, damaged DNA is worthless, leading directly to evolution's landfill. As a result, lambda activates its genes for replication, creates copies of itself, and then bursts outside the cell in search of additional healthy cells to infect.

Some phages use LexA, the infected cell's very own DNA damage sensor, to obtain information instead of using their own proteins to do so.

Proteins that bind to certain genetic patterns within the chromosome, the DNA instruction book, such as CI and LexA are transcription factors that switch genes on and off. Some phages, such as Coliphage 186, have discovered that they don't require their own viral CI protein if their chromosomes contain a brief DNA sequence that bacterial LexA can attach to. By triggering the phage's replicate-and-kill genes in response to DNA damage, LexA effectively double-crosses the cell into dying while enabling the phage to flee.

Researchers originally identified Coliphage 186's counterintelligence tactic in the late 1990s and the function of CI in phage decision-making in the 1980s. Several further cases of phages interfering with bacterial communication systems have since been made. One such instance is the phage phi29, which uses the transcription factor of its host to determine when the bacterium is about to produce a spore, or a type of bacterial egg that can endure harsh circumstances. When the spore germinates, Phi29 directs the cell to pack its DNA inside the spore, killing the developing bacterium.

My coworkers and I demonstrate in recently published research that many phage groups have independently evolved the capacity to access yet another bacterial communication system: the CtrA protein. To initiate several bacterial developmental processes, CtrA integrates a variety of internal and external cues. The development of flagella and pili, two types of bacterial appendages, is crucial among them. It turns out that these phages infect bacteria by attaching to the pili and flagella of the bacteria.

Our main theory is that phages use CtrA to predict when there will be enough pili- and flagellated bacteria in the area that they can easily infect. An intelligent move for a "mindless killer."

These phages are not the only ones that can make complex judgments without the aid of a brain. Each time they infect a cell, some phages that attack Bacillus bacteria create a tiny chemical. The phages can detect this chemical and utilize it to determine how many phage infections are present nearby. This count assists in determining when they should activate their replicate-and-kill genes, killing only when hosts are comparatively plentiful, much like extraterrestrial invaders do. By ensuring they never run out of victims to infect, phages ensure their own long-term survival.

Why you should be interested in the counterintelligence operations carried out by bacterial viruses is a valid question. Although bacteria and people are vastly different from one another, the viruses that infect them are not that dissimilar. The exploitation of virtually every tactic employed by phages by viruses that infect people has since been demonstrated. Why wouldn't a human virus tap your lines of communication if a phage can reach bacterial ones?

Although there are many plausible possibilities, scientists don't now know what human viruses would be listening for if they hijack these lines. I think human viruses might theoretically calculate their numbers to plan, detect cell proliferation and tissue construction, and even track immunological reactions, just way phages do. These scenarios are currently just conjecture, but scientific research is being done to find out.                                                                                                     

Although having viruses listening in on your cells' private discussions is not the best scenario, there is a bright side. Counterintelligence only functions when it is clandestine, as intelligence organizations around the world are well aware. Once discovered, the method is very readily abused to provide your adversary with false information. In a similar vein, I think that future antiviral treatments might be able to mix traditional weapons, such as antivirals that stop viral reproduction, with information warfare ploys, including tricking the virus into thinking the cell it's in is part of a different tissue.

Ivan Erill, an associate professor of biological sciences at the University of Maryland in Baltimore County, authored the article.

By IVAN ERILL, UNIVERSITY OF MARYLAND, BALTIMORE COUNTY