IMV Executive Assistant
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IMV Co-Director and Professor in the College of Biological Sciences
Reuben Harris, IMV Co-Director and professor in the University of Minnesota's College of Biological Sciences, has been awarded a five-year, $10 million grant from the National Institutes of Health to direct a large-scale research effort to study a human antiviral protein with potential for treating HIV and other viral diseases.
The goal of the study will be to produce atomic resolution images of the protein (APOBEC3G) to better understand how it interacts with other proteins in human cells and with HIV to prevent the virus from attaching to and entering cells. This fundamental knowledge could lead to novel methods to alter this protein to make it more effective.
“You have to understand the nuts and bolts of the system before you can make alterations to interfere with the process,” says Harris, an associate professor of biochemistry, molecular biology and biophysics. “I’m very optimistic that this will research will enable us to use this novel protein against HIV and other diseases.”
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.
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.
Institute for Molecular Virology
IMV investigators Dwight Anderson, Shelley Grimes, and Paul Jardine are investigating viral assembly and the description of biological motors at the molecular level. Both historically and experimentally, bacteriophages provide a perfect system to address both of these issues.
A molecular motor assembles transiently to the phi29 prohead capsid and packages DNA to near crystalline density, powered by ATP hydrolysis. The 174-base bacteriophage phi29 prohead RNA (pRNA) is essential for invitro packaging of the 19-kilobase pair DNA-gp 3 complex (DNA-g3) into the viral precursor capsid (prohead). pRNA is an integral part of the phi29 DNA packaging motor, one of the strongest molecular motors characterized, pRNA forms a novel cyclic hexamer by intermolecular base pairing of identical molecules. This multimer binds to the head-tail connector of the prohead, the core of the packaging motor, where it appears as a pentameric ring by cryoEM 3-D reconstruction.
A multimer of the packaging ATPase gp16 then binds the pRNA to complete the motor. pRNA is hypothesized to function in docking of the DNA-gp3 and the prohead, in recognition of the left end of DNA-gp3 to initiate packaging, and as a component of the DNA translocating ATPase. pRNA exits the DNA-filled head during neck and tail assembly, and it is not a part of the mature virion.
Study of the structure and function of this RNA-dependent DNA packaging motor may have general significance for assembly of other viruses, including mammalian viruses.
'Wisc-e-sota', the 1st Joint UMN-UW Virology Training Grant Symposium will be held on Friday, Sepbember 20th, 2013 at the Uniiversity of Wisconsin-La Crosse, Cartwright Center. This is the inaugural collaborative symposium of the NIH T32-supported virology training programs at the University of Wisconsin-Madison and the University of Minnesota-Twin Cities. Talks and poster sessions will be presented by students, postdocs and faculty.
The 2013 IMV Symposium was held in May, 2013 and featured Vincent Racaniello as the Keynote Speaker as well as the recording of an episode of 'This Week in Virology'. Pictures from the IMV Symposium can be found on the IMV Facebook page and a videotape of the TWiV podcast can be viewed at www.twiv.tv
Read about bacteriophage phi 29 and why it matters.
Explore nearly a century's worth of discovery in the field of virology at the University of Minnesota.
"This Week in Virology" from professor Vincent Racaniello.