Silent mutations in viruses could give birth to mechanisms to develop new and safer vaccines

 The IrsiCaixa HIV and HCV Genetic Variability group publishes this month in the journal Trends in Microbiology a review article on research in the field of "silent mutations", which are those that, at first, were believed to they were neutral but have recently been shown to have an effect on the structure of organisms. In their article, the IrsiCaixa group led by Miguel Ángel Martínez concludes that the manipulation of these mutations could have various utilities, such as attenuation of viruses to be used in vaccines or as gene therapy vectors , or they could also be used to delve deeper into a better understanding of the biology of viruses.

"Silent" or "synonymous" mutations are made by chemically synthesizing a genome. Research in this field is relatively new in biomedicine and has so far focused on the field of virology, because the genome of viruses is smaller and therefore easier to manipulate. At first it was believed that these mutations were neutral and did not cause any change in the set of hereditary characters of the virus, known as the phenotype, but it has been observed that, depending on the number of mutations and the region of the virus genome where they are introduced , they can attenuate it or even destroy it.

According to the Trends in Microbiology article , advances in this field have various applications, such as exploring the biology of viruses . Several studies carried out with HIV have recently shown that certain modifications in the silent sequence of the virus can completely modify its biology and even make it unviable. This can be applied to all viruses, called “persistent”, which, even if they are controlled, never disappear from the body. Research on the effect of synonymous mutations in HIV is one of the lines of research now being pursued by Dr. Martínez's group.

Attenuated viruses

Another possible utility of these mutations would be attenuated vaccines. Attenuated vaccines are those that contain infectious agents that have been cultivated under conditions under which they lose or attenuate their pathogenic properties, so that the microorganism can generate an immune response but its ability to produce disease is attenuated. Thus, when injected into a person, they do not become ill, but their immune system recognizes it and generates defenses against it.

The first attenuated vaccine was that of polio, in the 1950s, and since then a great variety has been developed, such as those for influenza, chikungunya, dengue or respiratory syncytial virus. "Now, the application of these synonymous mutations could allow us to develop much safer attenuated vaccines , which would make it possible to preserve all their ability to generate antibodies while ensuring that their application does not lead to the reversal of their virulence," explains Dr. Martínez.

Finally, research in this field could be applied to gene therapy, a treatment that consists of the introduction of specific genes into the cells of a patient in order to combat certain diseases. Its application was stopped a few years ago because the genes were introduced by means of vectors that used to be viral skeletons and could have some virulence. "Through silent mutations we could obtain much safer vectors that would allow us to resume this type of treatment, " says Martínez.