Inhibitors of the Interferon Response Increase the Replication of Gorilla Simian Foamy Viruses

Mathilde Couteaudier (1) , Diego Calzada-Fraile (1) , Thomas Montange (1) , Antoine Gessain (1) , Florence Buseyne (1)

1 EPVO (UMR_3569 / U-Pasteur_3) - Epidémiologie et Physiopathologie des Virus Oncogènes

Simian foamy viruses (SFVs) are complex retroviruses widespread throughout nonhuman primates. SFVs can also be transmitted to humans, mostly through bites. We previously observed that the primary zoonotic gorilla SFV strains much more slowly than laboratory-adapted chimpanzee strains. Here, we tested the hypothesis that SFV growth is limited by interferon (IFN)-induced restriction factors using inhibitors of cellular signaling pathways involved in type I IFN induction or action. Inhibitors of JAK1/2 (Ruxolitinib) and TBK-1 (BMX795) led to a 2 to > 20-fold higher percentage of infected BHK-1 and HT1080 cells. However, replication of the laboratory-adapted prototype foamy virus was not sensitive to these molecules, and IKK2 inhibitors had no effect on any of the SFV strains. In conclusion, the addition of small molecules that inhibit type I IFN response to the culture medium can be used as a simple and efficient method to enhance the replication of zoonotic gorilla SFVs

Keywords: interferon; foamy virus; immune response; Spumaretroviruses; Virus replication; Zoonosis

Domains: Adaptive immunology; Virology; Emerging diseases; Infectious diseases

Mathilde Couteaudier, Diego Calzada-Fraile, Thomas Montange, Antoine Gessain, Florence Buseyne. Inhibitors of the Interferon Response Increase the Replication of Gorilla Simian Foamy Viruses. Virology, 2019, 541, pp.25-31. ⟨10.1016/j.virol.2019.11.019⟩. ⟨pasteur-02418442v2⟩