Iron–sulfur clusters as inhibitors and catalysts of viral replication

• Published in: Nature chemistry 2022-03, Vol.14 (3), p.253-266
• Main Authors: Honarmand Ebrahimi, Kourosh, Ciofi-Baffoni, Simone, Hagedoorn, Peter-Leon, Nicolet, Yvain, Le Brun, Nick E., Hagen, Wilfred R., Armstrong, Fraser A.
• Format: Article
• Language: English
• Subjects: 631/250/262; 631/45/49/1141; 631/45/881; 639/638/45/49/1141; 639/638/92/612/1141; Analytical Chemistry; Biochemistry; Biochemistry, Molecular Biology; Catalysis; Catalysts; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Clusters; Cofactors; Immune response; Immune system; Immunology; Infections; Innate immunity; Inorganic Chemistry; Iron; Iron - metabolism; Iron sulfides; Iron-Sulfur Proteins - metabolism; Life Sciences; Metabolites; Neurodegeneration; Organic Chemistry; Physical Chemistry; Proteins; Replication; Review Article; Structural Biology; Sulfur; Viral infections; Virus Replication; Viruses
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/s41557-021-00882-0

A virus hijacks host cellular machineries and metabolites in order to reproduce. In response, the innate immune system activates different processes to fight back. Although many aspects of these processes have been well investigated, the key roles played by iron–sulfur [FeS] clusters, which are among the oldest classes of bio-inorganic cofactors, have barely been considered. Here we discuss how several [FeS] cluster-containing proteins activate, support and modulate the innate immune response to restrict viral infections, and how some of these proteins simultaneously support the replication of viruses. We also propose models of function of some proteins in the innate immune response and argue that [FeS] clusters in many of these proteins act as biological ‘fuses’ to control the response. We hope this overview helps to inspire future research in the emerging field of bio-inorganic virology/immunology and that such studies may reveal new molecular insight into the links between viral infections and diseases like cancer and neurodegeneration. Viruses use the cellular machinery of their host organism to reproduce. This Review discusses how [FeS] cluster-containing proteins activate, support and modulate the innate immune response to restrict viral infections as well as highlighting how some of these proteins simultaneously support the replication of viruses.