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We are interested in defining mechanisms of innate immune restriction and viral immune evasion, generating novel mouse models and understanding the epitope specificity of protective antibodies. Studies with viruses have focused on investigating their pathogenesis and the immune system response that controls infection. Using in vitro models of infection in primary neurons, macrophages, and dendtitic cells, we are studying the mechanisms by which viruses causes direct injury to specific target cell types, and how the host responds to limit viral replication.

We also study the structural and molecular bases of antibody-mediated protection of flaviviruses and alphaviruses, with a goal of identifying broadly neutralizing antibodies and their respective epitopes. Washington University in St. Louis Relocating to St. For coronavirus MHV-A59, comparable conformational change of the spike glycoprotein E2 S and cell fusion occurred at a mildly alkaline condition, suggesting that coronavirus infection-penetration, like that of paramyxoviruses and lentiviruses, may occur at the plasma membrane, rather than within endocytic vesicles.

Abstract We have obtained biochemical and electron microscopic evidence of conformational changes at pH 8. Publication types Research Support, U.

Many graduates of the Virology and Gene Therapy Track choose to pursue postdoctoral training regardless of whether they intend to pursue careers in academia or industry. Other students choose to enter advanced training programs like clinical microbiology and biochemical genetics programs. After graduating from the program, you could also choose to pursue a career in education, scientific writing and editing, or become a scientific grant program officer.

Several students from our laboratories have become tenured faculty and leaders in industry and in foundations. Our program works with other research and clinical programs at Mayo to facilitate rapid bench-to-bedside translation as well as easy access to clinical samples. Michael Barry, Ph.

College of Medicine and Science. Academics Section Overview Academic programs. Admissions and Tuition Section Overview Residencies and fellowships. About Section Overview College profile. Patient Care College Research. Virology and Gene Therapy Track. Bench-to-bedside thesis topics spanning basic virology and translational virology. Guaranteed 5-year internal fellowship includes full tuition, stipend and benefits. Current areas of research include: Molecular biology of viruses Mechanisms of virus-host interactions Gene therapy Oncolytic virotherapy Cancer immunotherapy Vaccine development Tissue engineering using viruses Genetic engineering using viruses.

Curriculum Students receive a comprehensive education in the biomedical sciences through a set of core courses. Year 1 Students are introduced to the laboratories participating in the program. For virus filtration, the IgG solution is prefiltered through a 0. Scale-down studies and virus validation studies were performed using similar equipment.

Test materials were transferred into specially designed, double-jacketed reaction containers, made from glass with a V-shaped bottom and connected to cooling or heating devices. Reaction containers were equipped with nozzles for adding test materials, reagents or for taking samples. The virus RNA, enveloped was propagated and titrated on C cells.

Human herpesviruses are not suitable for the studies due to interference by antibodies in human plasma. WNV is a relevant virus and its transmission by blood transfusion has been reported. It is propagated and titrated on KL-2 cells. BPV cross reacts with antibodies to B19 Parvovirus. This virus was used for virus filtration studies to test the potential influence of neutralizing antibodies on virus removal by virus filtration.

It is highly resistant to chemical or physical treatment. Virus titers are expressed as the negative decadic logarithm. Virus clearance was calculated by comparing the virus titers prior to and after the virus removal or inactivation step.

Virus validation studies addressed the worst case conditions Fig. Studies per step and virus were performed at least in duplicate to demonstrate the reproducibility of results.

Tests were performed at pH 5. The precipitated fraction III was removed by centrifugation and the supernatant was filtered through a depth filter and was tested for virus removal.

Same was done without depth filtration. Filtration was performed in dead end mode, where the feed is pumped directly against the filter membrane without any tangential flow. The conditions for validation of fraction III precipitation included lowering the ethanol concentration, shortening the precipitation time and increasing the temperature.

The virus reductions observed at pH 5. Validation of virus removal was tested at low pH of 5. Virus reductions were less than 1 log 10 at every condition tested and none of the data were used to estimate total virus clearance.

Conditions for validating the combined steps of fraction III precipitation and depth filtration Cuno of the fraction III supernatant were essentially the same as those used for each step performed separately.

Precipitation was performed at varied pH pH 5. Of these variations, pH changes were the only parameters that had a significant effect on virus removal. The minimum virus removal values at pH 5. Non-enveloped viruses, i. As shown in Table 2 , pH can influence the efficacy of virus removal by this step. Virus removal log 10 by precipitation and removal of fraction III at different pH, followed by depth filtration. The pH in validation studies was elevated to pH 6.

The temperature was reduced to Inactivation below the limit of detection of all viruses was achieved after 8 min treatment. The demonstrated inactivation values depend on the titer of the stocks of the different test viruses. Virus filtration studies were performed at high and low pH and with an excess of test sample with respect to filter surface area.

Values at high pH were reported in Table 1. During plasma fractionation, classes of proteins are precipitated and separated from proteins in solution by centrifugation or filtration.