Deciphering the role of giant virus GciS proteins in host cell iron-sulfur homeostasis – VirISC

Viruses are opportunistic parasitic pathogens that rely on hijacking host resources for survival and replication. The discovery of giant viruses revolutionized Virology and Biology in general due to their large, complex DNA genomes which encode thousand of proteins, most of them unique to each viral family and absent from the cellular world. These proteins may represent original metabolic pathways and adaptation strategies dating back to the origins of life.
The VirISC project focuses on a newly identified family of small iron-sulfur (Fe-S) proteins, named GciS, found in the large family Mimiviridae. These proteins, highly abundant in viral particles, have no known structure or function and share low complexity sequences with mostly glycine and cysteine residues. They are purified as large oligomers with exceptional Fe-S cluster binding properties, and mimic some features of the Fe-S carriers, which are key components of the cellular Fe-S assembly machinery. Our hypothesis is that GciS plays a role in Fe-S homeostasis by hijacking host Fe-S clusters during infection, redirecting them into viral (and/or cellular) proteins to modulate Fe-S-dependent metabolic pathways.
The principal goal of this project is to unravel the unique structural and functional properties of this novel viral Fe-S protein family and elucidate their physiological role. To achieve this, our multidisciplinary team brings together four partners with expertise in biochemistry, biophysics, cell biology, genetics, and virology. By addressing the fundamental role of and essentiality of Fe-S clusters in virology, an emerging research field, we aim to uncover new insights into viral evolution, potentially shedding light on early biochemical processes that shaped life on Earth. This project may also lead to innovative applications in biotechnology and medicine.