The Paramyxovirus family of viruses encompasses two sub-families and seven genera. Classified viruses within this family include the human pathogens measles, mumps, respiratory syncytial virus and human parainfluenza. Pathogens of animals are also significantly represented including rinderpest (now eradicated), peste des petits ruminants and Newcastle disease. There are also important emerging zoonotic viruses in this family including Hendra and Nipah. Collectively these viruses are a great health and economic burden across the globe resulting in numerous deaths and considerable hardship, yet there is a lack of effective vaccines and antivirals.
Paramyxoviruses all have non-segmented negative sense RNA genomes and are enveloped. This plasma membrane is itself stolen from the host cell during the process of virion release (budding). Embedded in the membrane of these viruses are virally encoded proteins that permit the attachment of the virus to uninfected cells and the subsequent entry of the viral genome.
The core aims of the Bailey laboratory are to improve understanding of paramyxovirus virology and basic cell biology and highlight the integral role of proteomics and systems biology in modern virology. Systematic analysis of the paramyxovirus family will improve knowledge of virus-host interactions, host restriction, pathogenesis and host range. This basic research will then be applied to the development of novel antivirals and vaccines.
Using novel proteomics techniques, as well as established molecular virology tools, the laboratory focuses on the following aspects of paramyxovirus biology:
Like all viruses the paramyxoviruses rely on hijacking cellular machinery in order to replicate and spread. Identifying the protein-protein and RNA-protein interactions underpinning this paradigm is an important focus of the laboratory. The Bailey laboratory has previously identified the epithelial receptor of a ruminant paramyxovirus (PPRV), an important step in understanding the molecular determinants of pathogenesis for this virus.
Attachment and entry:
The interaction between virus particles (virions) and their hosts (cells) is often determined by the specific affinities of viral attachment proteins for host receptors. The strength and specificity of these interactions plays an important role in determining the host range and cell-specificity (tropism) of viruses. This, in turn, has an important effect on the nature and severity of disease caused by the virus. Determining the restrictions and mechanism involved in these virus-host interactions is an on-going area of research in the Bailey laboratory.
Budding and release:
Paramyxoviruses have evolved two distinct strategies to spread from infected to uninfected cells. The classical strategy is via the formation and release of enveloped infectious particles while the other employs cell to cell fusion, allowing spread without virion production. Understanding the mechanisms behind these two processes is a key goal of the research in the Bailey laboratory.
Cytoskeleton and innate immunity:
The Bailey laboratory is also interested in examining the links between viral entry/exit and the innate immune response. We are particularly interested in how the cytoskeleton may provide the basis for this response.