Human infection with zoonotic simian foamy retroviruses (SFVs) : characterization of epitopic regions recognized by neutralizing antibodies in infected humans

Abstract

Background: Simian foamy viruses (SFVs) are ancient and wide-spread complex-type retroviruses that have co-evolved with their non-human primate (NHP) species for millions of years. These viruses can be transmitted to humans, primarily through bites, leading to the establishment of a life-long persistent infection. Despite frequent zoonotic transmission of SFVs from NHPs to humans in Central Africa and Asia, no overt pathology or human-to-human transmission of SFVs have been reported yet. My host laboratory hypothesized that the immune system efficiently controls viral replication in zoonotically infected humans. They demonstrated that neutralizing antibodies (nAbs) are present at high titers in Central African hunters infected with gorilla and chimpanzee SFV strains. My colleagues showed that two viral genotypes are circulating among SFV-infected NHPs and humans. A variant region within the surface domain (SU) of the viral envelope glycoprotein (Env), termed SUvar, forms basis of the two genotypes. The receptor binding domain (RBD) overlaps the SUvar region. The nAbs strictly target the SUvar region on the SFV Env. PhD project aims: I aimed to characterize nAb epitopes located within the SUvar region of SFV Env. Methods: To map nAb epitopes within SUvar, I performed neutralization assays in presence of recombinant SU proteins that compete with Env at the surface of viral particles for nAb binding. I used plasma samples from Central African hunters infected with gorilla SFVs and foamy viral vectors expressing SFV Env from each of the two genotypes. I generated mutant SU proteins by systematically deleting glycosylation sites, inserting glycans to disrupt epitope and by swapping residues between the two genotypes. Results: I have described that nAb epitopes have a genotype-specific location. Through collaborative work with the laboratory of Prof. Felix Rey who solved the crystal structure of a gorilla SFV RBD, we have discovered that most SFV-specific nA