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How do viruses decide whether to stay friendly?

This is how the decision-making mechanism of viruses works

A new study of Shemunis School of Biomedicine and Cancer Research at the George S. Wise Faculty of Life Sciences, deciphered the complex decision-making mechanism that allows the virus to choose whether to become violent or remain friendly to the bacterium it is in. Surprisingly, it turns out that the viruses use a system designed to protect the bacteria from them. As part of the study, the researchers show how the virus harnesses the bacterium's immune system, which is designed to fight viruses like it, to its aid, as part of this decision-making.

Don't bite the host!

The research was conducted under the leadership of Ph.D. student Polina Golar, from the laboratory of Prof. Avigdor Alder, at the Shmunis School, and with the cooperation of other laboratory members. The study was published in the leading scientific journal Nature Microbiology.

Bacteriophages, or "phages", are viruses that specialize in attacking bacteria for culture purposes. The name "bacteriophage" means "bacteria eater" in ancient Greek. However, despite their aggressive name, many phages can adopt a "quiet" mode of operation, in which the virus assimilates into the bacterium's DNA and remains dormant in it. In fact, in many cases it seems that in this mode of operation, the phages can even maintain a mutually beneficial relationship with their host bacteria.

According to Prof. Alder, phages actually tend to prefer to remain in the dormant state, where the bacterium takes care of their needs and helps them reproduce peacefully. As shown in a previous study, they decide whether to become violent in response to two types of information - the health status of the host, and signals received from the outside that indicate the presence of other phages in the environment.

"A phage cannot infect a bacterium that already contains another phage of the same type. So, in viral decision-making, if a phage detects that its host is damaged but also picks up signals that there are other phages around, it will choose to stay with the current host, hoping it will recover. If it doesn't recognize a signal from the outside, the phage 'realizes' that there may be a place for it in another host in the vicinity and then it will turn violent, kill its host and move on to the next victim."

The arms race between bacteria and viruses is stepping up

In the new study, Elder and his colleagues deciphered the mechanism that allows the virus to make these decisions. "We discovered that in this process, the phage actually uses the system that the bacterium developed to fight phages," says Ph.D. Polina Guler. When there are no external signals indicating the presence of other phages in nearby bacteria - the phage activates one strategy that neutralizes the bacterial defense system against it. "Then, when the defense system is neutralized, the phage goes into a violent state, replicates and kills its host," Goler describes the events. "However, if the phage receives a high rate of signals from the outside, it chooses the second strategy, and instead of neutralizing the defense system against it, it uses its attack to enter its sleep mode in the bacterium's genome, where the system no longer acts on it."

"The research reveals a new level of sophistication in the arms race between bacteria and viruses," adds Prof. Elder. "Until today, most of the research on the bacterial immune system has focused mainly on the confrontation of bacteria with violent phages only, and the mechanisms related to the interaction between bacteria and viruses in the dormant state remain much less known. "Bacteria also actually have an interest in keeping the viruses in a dormant state, first of all to survive, but also because the genes of the dormant phages may contribute to the function of the bacteria," he says.

"These findings are interesting for a variety of reasons. One reason is that there are bacteria, such as the bacterium that causes cholera, that become more virulent if they contain dormant phages. In these bacteria, the main toxins that the bacteria produce and cause us harm are actually encoded in the phage's genome, which is integrated into the bacteria's DNA," explains Prof. Alder. "In addition, phages can also be used as tools to fight bacteria and for that it is important to understand their mechanisms of action. Finally, we study phages to better understand how viruses work in general. Even many viruses that cause diseases in humans can switch between the active and dormant mode of action."

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