Area of Interest
Zoonotic viruses represent a potentially rich source of new emerging pathogens in humans, yet little information is available concerning the molecular, genetic and evolutionary mechanisms that regulate the establishment and dissemination of such a virus within a newly adopted host. Baric’s group is utilizing molecular, genetic and biochemical approaches to decipher the complex interactions between the virion and cell surface molecules that function in the entry and cross species transmission of positive strand RNA viruses. Using a highly species specific strain of mouse hepatitis virus (MHV), a model system has been developed to study virus cross species transmission under conditions that may be present in human xenograph recipients. Due to the lack of suitable organ donors, xenotransplantation will likely become the treatment of choice for end-stage organ failure in humans. Considerable debate exists as to whether this medical practice will result in new pathways for zoonotic virus adaptation to the human host. Baric’s group has demonstrated that xenotropic host range variants (MHV-H2) of MHV rapidly evolve in their experimental model suggesting that xenograph recipients may represent an optimum environment for virus cross species transmission. Viruses appear to bridge the species barrier by punctuated evolution and positive Darwinian natural selection at the molecular level resulting in virus recognition of phylogenetic homologues of the normal receptor for docking and entry into human cells.
Research projects currently study the evolutionary mechanisms that occur in viruses when subjected to changing environmental conditions. Baric’s team is also identifying the sites of virus-receptor interaction that regulate MHV-H2 entry into human cell lines and the mutations in the virus which expand host range specificity. Projects are also available to study virus cross species transmission in vivo in a small animal model for xenotransplantation.