To fight or prevent infections caused by viruses, it is essential to understand teh bond that these pathogens establish with their hosts, such as mosquitoes and humans. In this research, a group of Argentine scientists has shown that the vast majority of viruses use a strategy that influences genetic expression and that, contrary to what was believed, has to do with limiting the production of the necessary viral proteins to infect other cells.
The study in which this revelation was made is the work of a team composed, among others, of Ariel Bazzini, Luciana Castellano and Horacio M Pallarés, all three of the Stowers Institute for Medical Research in the American city of Kansas, as well as Andrea V Gamarnik, of the Leloir institute Foundation in Argentina.
the unexpected discovery “could help to better understand the evolution of host-pathogen interactions and, in the future, improve the design of vaccines to prevent viral infections,” Argentine researcher Ariel Bazzini, doctor, told CyTA-Leloir Agency. in biology who currently runs his own lab at the Stowers Institute.
To understand the scope of the work, it is indeed worth first remembering that ribosomes, structures present inside cells, are responsible for converting the genetic information carried by messenger RNA (mRNA) into proteins. That information is written using combinations of four letters (A, U, G, and C), but the ribosome only reads “words” made up of three of those letters. These words are called “codons”. Codons are like the specific ingredients (in this case amino acids) in a recipe to prepare a meal (in the exmaple proteins): for each codon the ribosome adds an amino acid to the chain that makes up a protein.
“For years we have been working on a genetic regulation mechanism called codon optimization, which has to do with the effect of each codon on the stability of the mRNA and its translation efficiency”, explained Bazzini, co-author. of the study. “The information about which codon corresponds to which amino acid is written in a universal genetic code, that is, almost all living things use the same code,” he added. He continued: “As different codons represent the same amino acid, we also speak of ’synonymous’ codons.The fascinating thing is that a few years ago we discovered that there is another layer of information in that genetic code, which has to do with the stabilization of the mRNA and the presence of what we call optimal and non-optimal codons.”
mRNAs enriched in optimal codons are more stable (persist longer and therefore produce more proteins), unlike those with suboptimal codons.
Argentine biotechnologist Luciana Castellano, phd student in the Bazzini laboratory and first signatory of the study, explained that they wanted to find out what type of codons the dengue virus uses. To do this, they downloaded thousands of genomic sequences of different isolates of that pathogen from existing databases.
“If we continue with the kitchen metaphor, there are different types of flour for making a cake. It would be better to use the leavening agent, as it is the most optimal for obtaining a larger volume. However, it is also possible to use 00 flour, even if the softness will not be optimal. Similarly, the virus could use both optimal and non-optimal codons to give rise to the amino acids of its proteins,” explained the scientist. “Our hypothesis – he continued – was that the dengue virus uses optimal codons to produce more viral proteins, but we found that, among all the possible synonymous codons, it preferentially uses the suboptimal ones. this surprised us, because since viruses are obligate intracellular parasites, they need a living cell to reproduce and use their host’s cellular machinery to produce viral proteins in order to infect other cells.”
How could this paradox be explained? Why would a cook prefer to use all-purpose flour instead of self-rising flour? “It could be a strategy to produce fewer viral proteins, perhaps to go unnoticed and not be detected by the immune system,” risked Castellano.
After determining this mechanism in dengue, the research team wanted to find out what type of codons other viruses use. “The vast majority of them, including SARS-CoV-2, HIV, influenza and zika, do the same thing: preferentially use suboptimal codons. So this is not an exclusive feature of the dengue virus,but is shared by hundreds of human viruses and shows that they do not care which codon to use,” Bazzini said,underlining that the study was carried out with the help of virologists Diego Álvarez,of the Biotechnological Research Institute of the National University of San Martin and CONICET,and Andrea Gamarnik,head of the Molecular Virology Laboratory of the Leloir Institute Foundation,in Argentina,all these institutions.
The study is titled “Dengue virus preferentially uses suboptimal human and mosquito codons.” And it was published in the academic journal Molecular Systems Biology, which highlighted this study on the cover.
The next step in this line of research will be to find out what the advantage is for the virus of using these suboptimal codons and which molecular mechanisms play a role in exercising this advantage, which could have repercussions on medical practice. (Source: CyTA-Leloir Agency)
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How could Dr. BazziniS findings impact future vaccine development against viruses like Zika or Dengue?
interview between Time.news Editor and dr. Ariel Bazzini
Time.news Editor: Welcome, Dr. Bazzini! It’s a pleasure to have you with us today. Your recent research on viral infections and host-pathogen interactions has garnered notable attention. Can you elaborate on the core findings of your study?
Dr. Ariel Bazzini: Thank you for having me! Our research revealed that many viruses adopt a strategy that fundamentally alters how their hosts express genes. Contrary to previous beliefs that viruses generally ramp up the production of viral proteins to propagate themselves, we discovered that they actually limit this production. This nuanced interaction provides insight into how viruses can stealthily navigate their host environments.
Time.news Editor: Fascinating! So, you’re suggesting that viruses are more strategic than previously assumed in their relationships with hosts like humans and mosquitoes?
Dr. Bazzini: Exactly. Our study indicates that by optimizing the way they interact with the host’s machinery—specifically by utilizing codon optimization—they can effectively manage their own replication process, all while minimizing detection by the host’s immune system.
Time.news Editor: That’s a compelling angle. For our audience, could you explain what codon optimization is and why it’s significant?
Dr. Bazzini: Certainly! Codon optimization refers to how specific sequences of nucleotides, or codons, within mRNA can influence the stability and efficiency of protein production. In our analogy, it’s like following a recipe to ensure you get the best meal possible. Viruses can manipulate these codons to either enhance or reduce protein synthesis, which is crucial for how well they can infect new cells.
Time.news Editor: That’s a great analogy! Given these discoveries, how might this understanding influence vaccine development in the future?
Dr. Bazzini: This research opens up new avenues for vaccine design. By understanding how viruses limit protein production and manipulate host responses, scientists can create more effective vaccines that preemptively block these strategies. Essentially, we could stimulate the immune system in a way that neutralizes these viral tactics.
Time.news Editor: It sounds like this research has the potential to significantly change the approach towards viral infections. Are there particular viruses or diseases that could benefit most from this new facts?
Dr. Bazzini: Absolutely. While our findings apply to a broad range of viral pathogens, we are especially hopeful for impactful developments related to viruses that cause widespread diseases, such as Zika or Dengue.Learning how these viruses modulate host responses could greatly enhance public health strategies.
time.news Editor: As a global community continues to wrestle with viral outbreaks, what message would you like to share with the public about the importance of this research?
Dr. bazzini: I would emphasize that science is a continuously evolving field. Our understanding of viral mechanisms is deepening, but there’s still much work to be done. Support for research is crucial,as it directly contributes to advancements in healthcare solutions and better responses to outbreaks. Every new finding brings us one step closer to more effective treatments and preventive measures.
Time.news Editor: Thank you, Dr. Bazzini, for sharing these insights. It’s inspiring to see how research can lead to improvements in public health strategies. We look forward to seeing how your work continues to unfold in the future.
Dr. Bazzini: Thank you! I appreciate the prospect to discuss our work, and I’m excited about what lies ahead.