Séminaire CIRI (27.06.2024): Veronika KRCHLIKOVA

Veronika KRCHLIKOVA, Mechanisms of Innate Antiviral Immunity, Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Elfriede-Aulhorn Str.6, 72076 Tübingen, Germany, “ Misdirected activity of antiviral proteins in pregnancy complications ”    

Abstract: Syncytin 1 and syncytin 2 are envelope glycoproteins encoded by human endogenous retroviruses. They have been exapted for the fusion of cytotrophoblast cells into syncytiotrophoblasts during placenta development. Interestingly, pregnancy complications have been associated with altered expression of syncytins or aberrant expression of interferons and interferon-stimulated genes such as antiviral restriction factors. In our study, we show that the antiviral activity of guanylate-binding protein 5 (GBP5) can be misdirected against syncytin 1. GBP5 inhibits the proteolytic activity of furin, thereby supressesing the cleavage and fusogenic activity of syncytin 1. In contrast, GBP5 does not inhibit syncytin 2 cleavage. Mechanistic analyses revealed that syncytin 2 cannot only be activated by furin, but also by its paralog PCSK7, which is resistant to GBP5. In line with this, we observed that the fusogenic activity of syncytin 1 can by partially compensated by syncytin 2. In summary, we here describe a mechanism of innate auto-immunity during pregnancy that impairs the activity of a co-opted retroviral envelope protein.

Hôte : Lucie Etienne