Karim Majzoub: The smallest virus raises the biggest questions

Karim Majzoub specializes in virology. In the wake of a global coronavirus pandemic, the relevance of his research is clear. The molecular biologist, who leads a research team at the Institute of Molecular Genetics in Montpellier (IGMM), works 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 animals, with 1,700 nucleotide base pairs (compared to about 30,000 for the coronavirus, for example). This virus, which encodes 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 plenty of reasons to be excited.

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 report the discovery of delta viruses in birds, reptiles, mammals, amphibians, and fish. With variants sometimes having very similar genomes in species that are otherwise very distantly related, these results support the hypothesis that this virus could cross the species barrier. Other findings published in 2019 and 2020: the delta virus can bind to surface proteins of viruses other than those of hepatitis B.

Building on these findings, Karim Majzoub contacted two research teams involved in the work: 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 for another ERC grant. Having been rejected for his first proposal on hepatitis, he succeeded with the one on delta viruses. 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 associate with other viruses to become infectious. The 1.5 million euros secured will fund five positions, including his own.

The Zika and dengue viruses

This ERC grant is also the culmination of a prolific scientific career—one that, to top it all off, regularly makes headlines. Between 2009 and 2013, Karim Majzoub worked on his thesis on the antiviral response in Drosophila at the University of Strasbourg, under the supervision of 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 complete a postdoctoral fellowship at Stanford University in California until 2018. There, starting in 2015, he used the cutting-edge CRISPR biotechnology to study the life cycles of the Zika and dengue 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, driven by considerations beyond just research: escaping the exorbitant cost of living—better suited to the salaries of Silicon Valley tech workers than to those of academics—and the education of his two daughters. A Marie Curie fellowship allowed him to join the Institute for Research on Viral and Hepatic Diseases in Strasbourg, then the IGMM in the summer of 2021. What can be said about this new southern home base?“It’s a perfect blend of Lebanon, California, and France!”concludes the Franco-Lebanese researcher.