Research Spotlight

Prof. James Lokensgard, Investigator

Institute for Molecular Virology

The Neuroimmunovirology laboratory is dedicated to understanding both protective and pathogenic neuroimmune responses during viral encephalitis. A number of independent research projects using several neurotropic viruses are currently underway. The first investigates host defense mechanisms against cytomegalovirus (CMV) brain infection. These experiments study how glial cell-produced chemokines recruit peripheral lymphocytes into the brain to control intracerebral viral spread, and are specifically dissecting the critical role of interleukin-10 and perforin-mediated cytotoxic activity. In additional experiments, we are studying CMV infection of neural stem cells and its effect on their subsequent differentiation. Other projects in the laboratory investigate the immunoregulation of herpes simplex virus (HSV) encephalitis by microglial cells. We are investigating how microglial cell-produced chemokines initiate cascades of neuroimmune responses that result in the serious brain damage seen during herpes encephalitis. We are attempting to modulate these pathogenic neuroimmune responses through the overexpression of anti-inflammatory mediators. We are also investigating HSV-induced production of neurotrophins and studying their role in repair of virus-induced brain damage. Knowledge gained through these studies will increase our basic understanding of virus-induced neuroinflammation and lead us towards our ultimate goal of developing new therapies for devastating viral brain infections.

Prof. Michael Murtaugh, Investigator

Institute for Molecular Virology

The Murtaugh laboratory seeks a comprehensive understanding of porcine immune responses to infectious pathogens, particularly persistent viruses. Porcine reproductive and respiratory syndrome virus (PRRSV) is the most important disease agent of swine worldwide. The porcine immune response to viral infection is deviates substantially from standard models of protective immunity. Viral clearance is a slow but inevitable process and is not dependent on neutralizing antibodies. Tools to assess the role of helper and cytotoxic T cells do not yet exist. Claims of immunosuppression and antibody-dependent enhancement further expand the possible consequences of PRRSV infection. The positive, single-stranded RNA genome mutates and recombines at a high rate to produce chimeric genomes and novel subgenomic RNAs. Understanding the biochemistry and molecular biology of genetic change will provide insights into fundamental mechanisms of viral evolution and radiation that may be related to the appearance of novel diseases in swine and other species. The results of our research will help the development of novel approaches for treatment of enteric illness and disease, and also will help to identify new pharmacological and immunologic targets capable of enhancing the efficacy of drugs and vaccines. We are also interested in other potentially significant persistent viral infections that appear nonpathogenic but might contribute to variation in penetrance of disease symptoms of agents such as PRRSV that typify infection. Porcine circovirus is a candidate infectious agent that does not reproduce disease on its own but might influence the consequences of PRRSV infection.