Paramyxoviridae is a family of non-segmented, negative-sense RNA viruses in the order Mononegavirales. These enveloped viruses replicate in the cytoplasm and infect a wide range of vertebrates. Examples of these infections in humans include parainfluenza viruses, measles virus, and mumps virus. J Paramyxovirus (JPV) was first isolated from feral mice with hemorrhagic lung lesions in Australia in 1972. In 2016, JPV, along with several other viruses, were placed into the newly proposed Jeilongvirus genus. Recently, many novel jeilongviruses have been discovered in wild mammals, indicating that these viruses are understudied. Both the in vitro and in vivo characterization of jeilongviruses is lacking. To address this, we first studied how jeilongvirus infection influences host gene expression using RNA-sequencing. RNA was collected from JPV-infected mouse fibroblasts at multiple timepoints after infection. This gave us a comprehensive overview of the transcriptional changes in host cells as infection progressed. The differentially expressed genes (DEGs) between the virus-infected cells and the mock-infected cells were determined at each timepoint. At 2 hours post-infection (hpi), there were only 11 DEGs, while 1,837 DEGs were detected at 48 hpi. A gene ontology (GO) analysis revealed that the genes upregulated at earlier timepoints were involved in innate interferon responses, while there was a shift towards genes involved in antigen processing and presentation processes at the later timepoints. Second, we investigated the role of the JPV syncytial protein (SP) in pathogenesis. All jeilongviruses possess a SP gene, which is not found in other paramyxoviruses. The JPV SP is required to promote cell-to-cell fusion in tissue culture cells. The role of SP in pathogenicity in vivo was not investigated before. The JPV virus lacking SP (rJPV-∆SP) was partially attenuated in mice, demonstrating that SP plays a role in pathogenicity. Lastly, we built upon the previously established JPV vaccine vector system by generating a novel JPV virus that is attenuated in vivo. We used this vector to generate a vaccine candidate for Nipah virus, an emerging zoonotic paramyxovirus that causes severe disease in humans. This works expands our knowledge about multiple aspects of jeilongvirus biology, from host-viral interactions to viral-vectored vaccine development.
