Karim Majzoub: the smallest virus asks the biggest questions

Karim Majzoub specializes in virology. After a worldwide pandemic linked to a coronavirus, the interest in his research is obvious. The molecular biologist, who heads a research team at the Montpellier Institute of Molecular Genetics(IGMM), is working on other viruses, such as hepatitis B and hepatitis D viruses. These viruses also represent a public health issue: over 200 million suffer from them worldwide.

For the past two years, he has been particularly fascinated by the delta virus responsible for hepatitis D. The smallest known virus in animal species, with just 1,700 nucleotide base pairs (compared with around 30,000 for coronavirus, for example). This virus, capable of encoding a single protein, is therefore entirely dependent on the host cell's functions for replication. And it also needs to associate with the hepatitis B virus to become an infectious agent, using the latter's surface proteins.

Jumping the species barrier?

" This organism at the very edge of life raises philosophical questions," enthuses the researcher, who has several reasons to be delighted.

His research is currently the subject of a great deal of scientific interest. With the massive sequencing of environmental samples made possible by new metagenomic approaches, numerous publications mention the discovery of delta viruses in birds, reptiles, mammals, amphibians and fish. In some cases, variants with very similar genomes have been found in very different species, leading to the hypothesis that this virus could jump the species barrier. Other results published in 2019 and 2020: the delta virus can associate with the surface proteins of viruses other than those of hepatitis B.

On the strength of these discoveries, Karim Majzoub contacted two teams involved: one in Finland, which had discovered a delta virus in a boa constrictor snake, and another in Germany, which had made a similar discovery in a panama rat. The new team then showed that delta viruses in rats and snakes replicate in human cells! These results prompted him to apply again for an ERC. Rejected for the first one on hepatitis, he succeeded with the one on delta viruses. This project should enable him to gain a better understanding of the host cell factors necessary for the replication of this virus, to find therapeutic targets for antiviral treatment, and also to understand how this virus can associate with other viruses to become infectious. The 1.5 million obtained will finance five positions, including his own.

Zika and dingue viruses

This ERC is also the culmination of a busy scientific career. A career that - not to spoil anything - is regularly in the spotlight. Between 2009 and 2013, Karim Majzoub completed his thesis on antiviral response in Drosophila at the University of Strasbourg, with Jean-Luc Imler, just a stone's throw from researcher Jules Hoffman, who was awarded the Nobel Prize in Medicine in 2011 for his work on the receptors responsible for innate immunity in insects. With his thesis in hand, he went on to do a postdoctorate at Stanford University in California until 2018. There, as early as 2015, he used the very latest Crispr biotechnology to study the life cycles of Zika and dingue viruses in human cells. A year later, the Zika epidemic broke out in Brazil.

In 2019, he finally left San Francisco with his family to return to France, with other considerations in mind than just research: escaping the exorbitant cost of living - more suited to the salaries of Silicon Valley geeks than academics - and the education of his two daughters. A Marie Curie fellowship enabled him to join the Institute for Research into Viral and Hepatic Diseases in Strasbourg, then the IGMM in the summer of 2021. What can she say about her new southern home? " It's a perfect synthesis of Lebanon, California and France ," concludes the Franco-Lebanese researcher.