During the first award period the MRCE Aerosol Biology/Small Animal Models Core D (Core D) supported smallpox disease research (using ectromelia, monkeypox, and vaccinia viruses) as this disease was one of the most intensely modeled in Region 7. With licensure of Modified Vaccinia Ankara (MVA) and the availability of ACAM 2000? (derived from Dryvax?), and phase I clinical trials of orthopoxvirus antivirals, ST-246 and CMX001, there is a diminishing need for in vivo testing of additional orthopoxvirus therapeutics and prophylactics. There is, however, still much to learn concerning the innate immune response to orthopxviruses and other infectious agents. The capacity of Core D to create additional models for use in basic research and prophylactic and therapeutic efficacy testing was under-scored by the development of the following five lethal challenge models: influenza virus A in C57BL/6-sfaH"A mice, monkeypox virus (MPXV) in C57BL/6-sfaf1"A mice and dormice, SARS-CoV in immunosuppressed hamsters, and B. anthracis in the A/J mice. Importantly, additional assays were implemented that characterized in greater detail disease progression (temperature by telemetry and blood levels of alanine aminotransferase (ALT) and virus genome equivalents) and the host response to infection (cytokines, NK cells, granulocytes, monocytes, and antigen specific CD4* and CD8+ T cells). Although Core D is capable of infecting animals through a full range of inoculation routes, it provides exceptional support for the use of respiratory routes of infection. The Core also has the capacity to aerosolize and deliver therapeutics to the respiratory tract for the study of early intervention strategies. The Core is one of the few academic facilities in the country to have the capacity to test therapeutics and prophylactics in compliance with GLP standards. Additional Core D services include: animal acquisition, protocol development, Institutional Animal Care and Use Committee (IACUC) protocol review, Institutional Biosafety committee (IBC) protocol review, health surveillance, husbandry, specimen collection, surgical services, clinical laboratory sample analysis, histology services, and report writing.
Specific Aim 1. Develop for investigators in the Regional Centers of Excellence small animal respiratory challenge models for Category A-C Priority pathogens and emerging infectious disease agents Specific Aim 2: Carry out respiratory small animal challenges and provide investigators with designated specimens, tissues and/or cells from small animals infected with various agents Specific Aim 3: Support preclinical testing of therapeutics and prophylactics for Category A-C Priority pathogens and emerging infectious disease agents

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Saint Louis
United States
Zip Code
Bandyopadhyay, Sarmistha; Long, Matthew E; Allen, Lee-Ann H (2014) Differential expression of microRNAs in Francisella tularensis-infected human macrophages: miR-155-dependent downregulation of MyD88 inhibits the inflammatory response. PLoS One 9:e109525
Virgin, Herbert W (2014) The virome in mammalian physiology and disease. Cell 157:142-50
Bialasiewicz, Seweryn; McVernon, Jodie; Nolan, Terry et al. (2014) Detection of a divergent Parainfluenza 4 virus in an adult patient with influenza like illness using next-generation sequencing. BMC Infect Dis 14:275
Rasmussen, Jed A; Post, Deborah M B; Gibson, Bradford W et al. (2014) Francisella tularensis Schu S4 lipopolysaccharide core sugar and O-antigen mutants are attenuated in a mouse model of tularemia. Infect Immun 82:1523-39
Patel, Dhara A; Patel, Anand C; Nolan, William C et al. (2014) High-throughput screening normalized to biological response: application to antiviral drug discovery. J Biomol Screen 19:119-30
Rohatgi, Anjali; Corbo, Joseph C; Monte, Kristen et al. (2014) Infection of myofibers contributes to increased pathogenicity during infection with an epidemic strain of chikungunya virus. J Virol 88:2414-25
Ermler, Megan E; Traylor, Zachary; Patel, Krupen et al. (2014) Rift Valley fever virus infection induces activation of the NLRP3 inflammasome. Virology 449:174-80
Moorman, Nathaniel J; Murphy, Eain A (2014) Roseomics: a blank slate. Curr Opin Virol 9:188-93
Canny, Susan P; Reese, Tiffany A; Johnson, L Steven et al. (2014) Pervasive transcription of a herpesvirus genome generates functionally important RNAs. MBio 5:e01033-13
Barker, Jason H; Kaufman, Justin W; Zhang, De-Sheng et al. (2014) Metabolic labeling to characterize the overall composition of Francisella lipid A and LPS grown in broth and in human phagocytes. Innate Immun 20:88-103

Showing the most recent 10 out of 257 publications