Viral entry. Within the Paramyxoviridae family, Nipah virus (NiV) and Hendra virus (HeV) cause the highest mortality rates (40-100%) in humans. This viral family includes important human and veterinary pathogens, such as measles, mumps, human parainfluenza, canine distemper, and Newcastle disease viruses. There are many questions in the paramyxoviral entry field that remain elusive. Our recent studies have identified several novel regions in the viral glycoproteins G and F that are important for modulating viral-cell membrane fusion during viral entry, as well as cell-cell fusion after a virus has infected a cell. What steps in the viral entry process these regions in G and F modulate is an important question we pursue. We use novel approaches that allow us to study the steps of viral entry, such as receptor binding, fusion triggering, hemifusion, fusion pore formation, and syncytia formation on cells and on virions. Novel approaches include Flow Virometry and Raman Spectroscopy.
Viral structures, assembly, and egress. Using multi-omics approaches, we have identified cellular factors involved in viral entry, assembly, and budding. We use this knowledge to study the mechanisms by which viral and cellular factors interact to modulate viral assembly and egress from infected host cells. Importantly, we connect this knowledge to the study of viral pathogenesis via established biosafety level 4 collaborations. Via Cryo-EM we analyze the structures of full virions, viral-like particles, and glycoproteins to illuminate our understanding of viral entry, assembly, and egress.
Immune responses and vaccine development. Viral-like particles are non-replication-competent units that resemble the respective actual viruses. Our laboratory studies various types of viral-like particles to simultaneously incorporate multiple viral glycoproteins. Our lab has shown that NiV and HeV viral-like particles are useful to generate highly-neutralizing conformational antibodies to these viruses. We investigate the usefulness of viral-like particles and pseudotyped viral particles as vaccine platforms to protect against NiV, HeV, and other emerging paramyxoviruses and viruses beyond this family. We also have novel ways to kill viruses that preserve their conformations for vaccine development.
Antivirals. We take both empirical and targeted approaches. Our main interests include the search for antiviral agents with broad antiviral applications, with a special interest in those to be used against enveloped viruses. Our membrane fusion studies foster the discovery of broad-spectrum antivirals that target enveloped viruses. We are currently characterizing the mechanisms of action of several broad-spectrum antivirals against various families of enveloped viruses.