A VSV-based pseudotyping system for studying entry and neutralization of papiine alphaherpesvirus 2

Abstract Simplexviruses of non-human primates differ in their capacity to cause severe disease in humans. Papiine alphaherpesvirus 2 (PaHV-2) of baboons has not been reported to be pathogenic in humans while human infection with macacine alphaherpesvirus 1 (McHV-1, Herpes B Virus) can cause fatal disease. In order to study PaHV-2 entry into cells, we established a pseudotyping system based on vesicular stomatitis virus (VSV). For this, the genes coding for core glycoproteins of PaHV-2, gD, gH, gL and gB as well as gC were cloned and the glycoproteins were equipped either with the native signal peptide or a heterologous signal peptide and an epitope tag. Glycoproteins with Igκ-signal peptide were most robustly expressed and incorporated into pseudotyped VSV particles. VSV bearing the core glycoproteins (DHLB pp ) or an extended set of glycoproteins (DHLBC pp ) efficiently entered several cell lines of human, rhesus macaque, African green monkey and mouse origin. In addition, DHLB pp were efficiently neutralized by baboon sera at levels comparable to those determined with a PaHV-2 reporter virus. In summary, VSV particles bearing glycoproteins of PaHV-2 are a novel tool to study PaHV-2 entry and neutralization.