Inhibitors of the interferon response increase the replication of gorilla simian foamy viruses

Abstract

Simian foamy viruses (SFVs) are complex retroviruses that are widespread throughout nonhuman primates. SFVs can also be transmitted to humans, mostly through bites. We previously observed that primary zoonotic gorilla SFV strains grow much more slowly than laboratory-adapted chimpanzee strains. Here, we tested the hypothesis that the growth of SFV is limited by interferon (IFN) using inhibitors of cellular pathways involved in the induction or action of type I IFN. Inhibitors of JAK1/2 (Ruxolitinib) and TBK-1 (BX795) led to a 2- to 4-fold higher percentage of cells infected with zoonotic gorilla SFVs but did not affect the replication of laboratory-adapted chimpanzee SFVs. IKK2 inhibitors (TPCA-1 and BMS345541) had no effect on any of the SFV strains. In conclusion, the addition of molecules that inhibit the 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: Foamy virus; Immune response; Interferon; Spumaretroviruses; Virus replication; Zoonosis.