A major goal of emerging infectious disease research is to acquire the ability to predict when, where and under what conditions new infectious agents will emerge, and to evaluate the risk they may pose for public health. One example of emerging pathogens are the zoonotic Arenaviruses, which are endemic to Africa, as well as North and South America, where they cause severe hemorrhagic fevers.
Risk assessment and prediction of virus emergence requires a deeper understanding of not only the molecular determinants of virulence, but also the diversity and evolution of virus populations and virus ecology. In particular, insight into determinants of virus virulence is complicated by the observation that for many virus families, including the arenaviruses, there are non-pathogenic/low virulence virus species (i.e. Tacaribe, Amapari and Cupixi virus) that are genetically very closely related to highly pathogenic agents (i.e. JunÍn, Machupo and Guanarito virus). The reason for this difference in phenotypes is mostly unknown, and thus our ability to assess the risk posed by newly discovered virus species is significantly limited. Further, new arenaviruses species are being discovered around the world, including significant pathogens. At the same time the endemic regions for several of these viruses seem to be expanding, with little knowledge about what drives this expansion or how far these endemic regions might eventually spread.
The research in the Arenavirus Biology lab will address these issues by combining laboratory research, field work and computational biology to explore the genetic diversity and geographical distribution of arenaviruses in nature, as well as the viral attributes that contribute to their virulence, and the role of virus-host interactions in pathogenesis.
In particular, we are interested in understanding the role that sensing of an infection by the host cell at various levels (i.e. by innate immune as well as apoptotic pathways) plays in eliciting virus species specific responses that may contribute to control of infection. Further, using reverse genetics-based lifecycle modelling systems (i.e. minigenome and trVLP assys) that allow us to recapitulate specific subsets of steps in the virus lifecycle, we aim to identify specific host proteins that support or restrict virus infection. This not only provides much needed insight into virus biology, but allows identification of potential targets for the development of novel antiviral therapies. Finally, these lifecycle modelling systems have tremendous potential for the development of new virus discovery platforms, and their application in the field could potentially expand our understanding of arenavirus genetic diversity and lead to improvement in our understanding of the ecology and evolution of these viruses.
- Mechanisms of apoptosis induction and evasion during infection
- Identification of host cell factors that support and restrict virus infection
- Development of novel platforms for new virus discovery