Karim Majzoub: The Smallest Virus Raises the Biggest Questions for Him

Karim Majzoub specializes in virology. In the wake of a global coronavirus pandemic, the relevance of his research is self-evident. The molecular biologist, who leads a research team at the Montpellier Institute of Molecular Genetics (IGMM), is working on other viruses: hepatitis B and hepatitis D. These viruses also pose a public health challenge: more than 200 million people worldwide are infected with them.

For the past two years, he has been particularly fascinated by the delta virus, which causes hepatitis D. It is the smallest known virus in animal species, with 1,700 nucleotide base pairs (compared to about 30,000 for the coronavirus, for example). This virus, which is capable of encoding only a single protein, is therefore entirely dependent on the host cell’s functions to replicate. It also needs to associate with the hepatitis B virus to become infectious, using the latter’s surface proteins.

Breaking the species barrier?

“This organism, which exists on the very edge of life, raises philosophical questions!” exclaims the researcher, who has several reasons to be delighted.

His research is taking place against a backdrop of rapid scientific developments. With the large-scale sequencing of environmental samples made possible by new metagenomic approaches, numerous publications have reported the discovery of delta viruses in birds, reptiles, mammals, amphibians, and fish. In some cases, variants with very similar genomes have been found in species that are otherwise very distantly related—findings that support the hypothesis that this virus could cross the species barrier. Other findings published in 2019 and 2020 indicate that the delta virus can bind to surface proteins of viruses other than those of hepatitis B.

Building on these findings, Karim Majzoub contacted two teams involved in the research: one in Finland that had discovered a delta virus in a boa constrictor, and another in Germany that had made a similar discovery, this time in a Panama rat. The new team then demonstrated that the delta viruses in the rat and the snake replicate in human cells! These results prompted him to apply once again for an ERC grant. Although his first application, on hepatitis, was rejected, his second, on delta viruses, was successful. This project aims to help him better understand the host cell factors necessary for the replication of this virus, identify therapeutic targets for antiviral treatment, and understand how this virus can combine with other viruses to become infectious. The 1.5 million obtained will fund five positions, including his own.

The Zika and Dengue Viruses

This ERC grant is also the culmination of a rich scientific career—one that, to top it all off, regularly makes headlines. Between 2009 and 2013, Karim Majzoub worked on his dissertation on the antiviral response in Drosophila at the University of Strasbourg, under the guidance of Jean-Luc Imler, just a stone’s throw away 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 Ph.D. in hand, he went on to complete a postdoctoral fellowship at Stanford University in California until 2018. There, beginning in 2015, he used the then-new CRISPR biotechnology to study the life cycles of the Zika and dengue viruses in human cells. A year later, the Zika outbreak began in Brazil.

In 2019, he finally left San Francisco with his family to return to France, with other considerations in mind besides just research: escaping the exorbitant cost of living—more suited to the salaries of Silicon Valley techies than to those of academics—and the education of his two daughters. A Marie Curie fellowship enabled him to join the Institute for Research on Viral and Hepatic Diseases in Strasbourg, and then the IGMM in the summer of 2021. What can be said about this new home in the south?“It’s a perfect blend of Lebanon, California, and France!”concludes the Franco-Lebanese researcher.