Neutralization of zoonotic simian foamy viruses: genotype-specific epitopes within the receptor-binding domain

Simian foamy viruses (SFVs) are retroviruses that are frequently cross-transmitted to humans. SFVs establish life-long infection in their human hosts, with the persistence of replication-competent virus. Zoonotic SFVs do not induce severe pathology and are not transmitted between humans. Infected individuals develop potent neutralizing antibodies (nAbs) that targets the SFV envelope protein (Env). Env carries a variable region that defines two SFV genotypes and is the exclusive target of nAbs. However, its antigenic determinants are not understood. Here, we characterized nAbs from SFV-infected individuals living in Central Africa. The nAbs target conformational epitopes within two major antigenic areas located at the Env apex: One mediates the interaction between Env protomers to form Env trimers and one harbors several determinants of Env binding to susceptible cells. One binding determinant is genotype-specific. We propose a model integrating structural, genetic, functional, and immunological knowledge on the SFV receptor binding domain. ### Competing Interest Statement The authors have declared no competing interest.