The central focus of our research is the synthesis, folding, processing, trafficking and assembly of viral proteins, with an emphasis on the glycoproteins. Previous studies of the synthesis and processing of viral glycoproteins in the secretory pathway have led to fundamental discoveries of basic cellular processes, and our research on the folding, processing and trafficking of paramyxovirus glycoproteins provides insight into both cellular functions and important viral protein functions. Our studies on viral proteins aim to elucidate mechanisms of promotion of membrane fusion and assembly, and to provide new targets for antiviral treatments.
Many major human pathogenic viruses (including HIV, herpes simplex virus, measles virus, Ebola virus and Zika virus) are packaged in a membrane. In order for these viruses to infect cells, specific viral proteins promote fusion of the viral membrane with the membrane of the host cell. Understanding this process of protein-mediated membrane fusion is one of the major focuses of our work. Over the past years, viral fusion proteins have also been shown to play an important role in assembly and exit of the virus from the cells, which is another focus of our work. To understand these basic processes, we use as a model fusion proteins from several different paramyxoviruses. First, we are examining the fusion protein from the Hendra and Nipah viruses, newly emerged diseases in the paramyxovirus family that are highly pathogenic in multiple species including humans, and which are classified as Biosafety Level 4 pathogens. Our laboratory has identified cathepsin L, a cellular endosomal/lysosomal protease, as critical protein for activation of the Hendra and Nipah fusion proteins, and thus a potential drug target. We are also studying the F protein from the paramxyovirus PIV5, for which multiple mutants have been made and for which several atomic structures are now known. Finally, we study the glycoproteins from human metapneumovirus (HMPV), a recently identified virus that is a causative agent of severe respiratory disease in infants and young children. Our long-term goal is to understand the specific molecular events in these important viral life cycle processes.