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The world’s smallest terrorist: Virus hijacks protein machine and then kills the host

The world's smallest terrorist: Virus hijacks protein machine and then kills the host

Bacteriophages are viruses that infect and kill bacteria. The name originates from the Greek ‘phagos’ which means ‘to devour’. Bacteriophages were discovered 100 years ago because of their ability to replicate in a pathogenic bacterium, kill it and thereby cure the patient. As a small spaceship landing on the moon, the microscopic particles land on the surface of the bacteria where they inject their deadly genetic material.

In fact, virus is nothing but small protein capsules enclosing the genetic material. The virus cannot replicate without a host cell, which it hijacks for its survival. During an infection, it utilises its host cell’s metabolism to make lots of copies of the virus, which are subsequently released, and infect new host cells while the host cell dies.

An international team of researchers from Denmark and Russia used a series of biochemical and structural biology techniques to investigate how the Qβ bacteriophage, which infects the common coli bacteria, utilises several of its host cell’s proteins while replicating its genetic material.

Immediately after infection, Qβ releases its genetic material into the host cell, where it is used as a template for the production of viral proteins. Qβ takes over the host cell’s protein machine to synthesise its envelope proteins, as well as a virus-specific RNA polymerase, called a replicase. The task of the replicase is to replicate the virus’ genetic material, whereas the host cell’s genetic material is not to be recognised and copied.

The replicase cannot cope with this task on its own, so it hijacks three ‘helpers’ from the host’s own proteins namely the ribosomal protein S1, EF-Tu and EF-Ts, which all usually play important roles for the host cell’s protein machine.

In a recently published work, the researchers have shown how ribosomal protein S1 plays a crucial role when the viral Qβ genetic material is to be distinguished from the genetic material of the coli bacteria prior to the replication process. Together, the replicase and S1 form a surface to which the viral genetic material is likely to bind during the recognition process. If this surface is mutated on the replicase, it loses its ability to accurately recognise the virus genome, which has fatal consequences for the virus, which can no longer replicate.

In the future, these findings may form the basis for the development of new methods for treating viral infections, as the majority of all virus faces a similar challenge, namely to have to selectively replicate its own genetic material in competition with the genetic material of the host cell. If this strategy fails, the virus will lose its ability to spread to new host cells and the infection will then be stopped.

Gytz H, Mohr D, Seweryn P, Yoshimura Y, Kutlubaeva Z, Dolman F, Chelchessa B, Chetverin AB, Mulder FA, Brodersen DE, & Knudsen CR (2015). Structural basis for RNA-genome recognition during bacteriophage Qβ replication. Nucleic acids research PMID: 26578560

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