Henipaviruses (HNVs), such as Nipah virus (NiV) and Hendra virus (HeV), circulate in bats across Southeast Asia and Australia and cause severe disease when they spill over into humans. Due to their risk to human health, research with NiV and HeV is restricted to high containment (BSL-4) laboratories. Outside of Southeast Asia, serological and metagenomic evidence has recently identified African fruit bats as reservoirs of novel HNVs. In 2012, a metagenomic survey identified a novel henipavirus, Ghana virus (GhV, strain M74a), from Eidolon helvum bats. Attempts to isolate GhV in culture have remained unsuccessful, however, limiting our understanding of its biology and its potential risk to human health. In Chapter 2, we developed a BSL-2 life-cycle modeling system for HNVs; however, efforts to extend this system to GhV revealed that the available genome sequence is incomplete and lacks a genomic promoter. However, substitution of the unmapped sequence with analogous region from HeV was sufficient to restore a functional promoter for GhV, facilitating replicase activity in minigenome. In Chapter 3, we build upon this approach, using reverse genetics to recover a full-length, infectious clone of GhV de novo at BSL-4. This virus enabled us to conduct in-depth characterization of the tropism, replication, pathogenicity, and zoonotic risk of GhV. Profiling GhV replication across human, porcine, and bat cell lines revealed that GhV is highly adapted to its bat vi hosts. Furthermore, we demonstrate that GhV does not cause disease in Syrian golden hamsters. In agreement with GhV attenuation in vivo, utilization of a chimeric, Ephrin-B3 blind virus ultimately revealed that Ephrin-B3 usage is a major determinant of HNV pathogenesis. In Chapter 4, we develop a replicon system for NiV which decoupled the processes of replication and transcription from virus budding and spread. Using AlphaFold3 modeling, we predict the mechanism of HNV genome packaging and demonstrate that an absolutely conserved arginine (R172) in matrix protein is essential for packaging viral ribonucleoprotein complexes into viral particles. Collectively, these data significantly advance our understanding of paramyxovirus biology and establish versatile, accessible platforms for study of emerging zoonotic viruses.