Especially after more than two years of COVID-19 pandemic, many people imagine the virus as a nasty, unconscious killing machine that enters a cell and hijacks its machine, creating countless copies of itself before it breaks out.

viruses may be "monitoring" you - some microorganisms are waiting until their host inadvertently signal them, and then start reproduction and killing them. Especially after more than two years of the COVID-19 pandemic, many people imagine the virus as a nasty, unconscious killing machine that enters a cell and hijacks its machine, creating countless copies of itself before it breaks out. For many viruses, including the coronavirus that causes COVID-19, the title of "brainless killer" is basically real. However, the biological properties of the virus are not as seen.

A suitable example is HIV, the virus that causes AIDS . HIV is a retrovirus that does not kill immediately when it enters a cell. Instead, it integrates itself into the human chromosomes and treats it coldly, waiting for the right opportunity, ordering the cells to replicate it, and bursting out to infect other immune cells , eventually leading to the onset of AIDS.

phage, or phage for short, is a naturally occurring virus that attacks and kills bacteria but cannot infect human cells. Phages are extremely diverse and are everywhere in the environment, including our bodies. In fact, humans contain more phages than human cells.

phage has three main parts: a head, a sheath and a tail. Phages use their tails to attach to bacterial cells.它们利用细菌来复制自己。 After finding a "matched" bacterial cell, the phage injects its genetic material, hijacking the system commonly used for bacterial reproduction. Instead, the system will create thousands of phages that will eventually blow up bacterial cells and release them into the environment.

It is not clear exactly when HIV is waiting for, because this is still an area of ​​active research. However, studies on other viruses have long shown that these pathogens can be quite "ideas" in killing. Of course, the virus cannot think like you and I. However, evolution has proven that they have given some rather fine decision-making mechanisms. For example, some viruses will choose to leave the cells they have been living in if they detect DNA damage. It seems that even viruses don't like staying in a sunken ship.

For more than two decades, researchers have been studying phages' molecular biology . Recent studies have concluded that phages can listen to key cellular signals to help them make decisions, and they can even use the cells' own "ears" to listen to them.

Escape DNA damage

If your enemy's enemy is your friend, then phage is definitely your friend. 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 bacteriophage λ, which acts a bit like HIV. After entering the bacterial cell, the lambda decides whether to replicate and kill the cells like most viruses, or integrate itself into the chromosomes of the cells like HIV. If it is the latter, each time the bacteria divides, λ will replicate harmlessly with its host.

This video shows a λ phage infected with E. coli

However, like HIV, lambda is not just idle. It uses a special protein called CI, which listens like a stethoscope to listen to signs of DNA damage in bacterial cells. If the bacteria's DNA is damaged, this is bad news for the lambda phage nested in it. The damaged DNA leads directly to the evolutionary dump because it is useless for phages that need it to reproduce. Therefore, λ turns on its replicated gene, replicate itself, and rush out of the cells, looking for other undamaged cells to infect.

Communication system for mining cells

Some phages do not collect intelligence with their own proteins, but use the infected cells' own DNA damage sensor. Proteins like CI and LexA are transcription factor , which turn genes on and off by binding to specific genetic patterns in DNA instructions (i.e., chromosomes).Some phages such as Coliphage 186 have found that if they have a short DNA sequence on their chromosomes, which bacterial LexA can bind, then they do not need their own viral CI protein. When DNA damage is detected, LexA will activate the replication and killing genes of the phage, essentially a double crossover that allows the phage to escape while allowing the phage to escape.

researchers first reported the role of CI in bacteriophage decision-making in the 1980s and reported the counterintelligence techniques of Coliphage 186 in the late 1990s. Since then, there have been reports on bacteriophage conquering bacterial communication systems. An example is the bacteriophage phi29, which uses its host's transcription factors to detect when a bacteria is ready to produce spores, or a bacterial egg that can survive in extreme environments. Phi29 instructs the cells to package their DNA into the spores, which kills the budding bacteria once the spores germinate.

video shows the genes that transcription factors are turned on and off. In a recently published study, several groups of phages have independently evolved the ability to utilize another bacterial communication system: the CtrA protein. CtrA integrates multiple internal and external signals to initiate different developmental processes of bacteria. The key is the production of bacterial appendages called flagella and cilia. It turns out that these phages attach themselves to the bacteria's cilia and flagella in order to infect them.

The main assumption is that phages use CtrA to guess when there will be enough bacteria that motile cilia and flagella nearby that can easily be infected. This is a pretty clever trick for an "unconscious killer".

These are not the only phages that make careful decisions - all of which do not require a brain. Some phages infected with Bacillus produce a small molecule each time they infect one cell. Phages can sense this molecule and use it to calculate the number of phage infections that occur around them. Like alien invaders, this count helps determine when they should turn on their replication and killing genes, killing only when there are relatively many hosts. In this way, phages can ensure that they will never have a host to be infected and ensure their own long-term survival.

Counter-espionage against viruses

A good question is why you should care about the anti-intelligence operation carried out by bacterial viruses. Although bacteria are very different from humans, viruses that infect bacteria are no different from viruses that infect humans. Almost every trick played by phages was later proven to be used by viruses infected with humans. If phages can steal bacteria's communication lines, why can't human viruses steal yours?

So far, scientists don't know what human viruses will listen to if they hijack these lines, but there are many conceivable options. It is believed that like phages, it is possible that human viruses can count their numbers to develop strategies, detect cell growth and tissue formation, and even monitor immune responses. At present, these possibilities are just speculations, but scientific research is under investigation.

Letting viruses monitor your cells' private conversation is not the best picture, but it is not without a glimmer of hope. Intelligence agencies around the world are well aware that counterintelligence work can only work in concealment. Once discovered, the system can be easily exploited to provide error information to your enemies. Similarly, I believe that future antiviral therapies may be able to combine traditional therapeutic measures such as antiviral drugs that prevent virus replication with the ruse of information warfare, such as making the virus believe that the cells it is located belong to different tissues.