The Projects within this Center study the interplay between Ectromelia virus (ECTV), the causative agent of mousepox (the smallpox of the mouse), and its natural host, the mouse. The interplay between ECTV and the immune system of the host can take place at many different levels. It can occur at a tissue level, in which release of immune mediators such as type I interferons alter infection in the skin (Project 1) or lymph node, spleen and liver (Project 2) by ECTV., It can also occur at the cellular level, in which immune cell infiltration and interaction with ECTV infected cells will alter virus replication and spread (Project 1, 3). Finally, it can occur at an intracellular level, in which the trafficking of internalized ECTV, and the endocytic routes used during ECTV infection, can alter the mechanisms by which the immune system senses infection (Project 3 + Aim 2 of this Core). This Core (C) will allow the visualization of all of these events, by providing timely, cost-effective and expert histology and microscopy support for all three Projects within the Center. The equipment and expertise that will be provided by this Core are aimed at reducing the startup time and degree of expertise that would be necessary for individual users if they were required to design and execute experiments and image processing. In addition, the Core will allow imaging of live virus in Biosafety Level 2 containment, which is not possible in shared facilities. In addition to providing support for all three Projects, Aim 2 of this Core will investigate an area of research that bridges areas of investigation in Projects 1 and 3, namely the endocytic processes involved in ECTV internalization and infection, and the presentation of virus-derived components in complex with MHC Class II. Thus, the Core will enhance both the scientific capabilities of the Center and will foster interactions between the individual Projects.
We anticipate that the insight we gain into the mechanisms that prevent a peripheral virus infection from spreading systemically will aid understanding^ of the ^mechanisms deployed against many viruses of importance to human and animal health such as Enterovirus (polio, cocksackie), Aphtoviruses (foot-andmouth disease), Rubivirus (rubella), Flavivirus (Yellow Fever, Dengue, West Nile), Rubulavirus (mumps), Morbillivirus (measles), Varicelovirus (chickenpox).
|Remakus, Sanda; Ma, Xueying; Tang, Lingjuan et al. (2018) Cutting Edge: Protection by Antiviral Memory CD8 T Cells Requires Rapidly Produced Antigen in Large Amounts. J Immunol 200:3347-3352|
|Norbury, Christopher C (2016) Defining cross presentation for a wider audience. Curr Opin Immunol 40:110-6|
|Sei, Janet J; Haskett, Scott; Kaminsky, Lauren W et al. (2015) Peptide-MHC-I from Endogenous Antigen Outnumber Those from Exogenous Antigen, Irrespective of APC Phenotype or Activation. PLoS Pathog 11:e1004941|
|Fang, Min; Remakus, Sanda; Roscoe, Felicia et al. (2015) CD4+ T cell help is dispensable for protective CD8+ T cell memory against mousepox virus following vaccinia virus immunization. J Virol 89:776-83|
|Xu, Ren-Huan; Wong, Eric B; Rubio, Daniel et al. (2015) Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection. Immunity 43:1148-59|
|Kaminsky, Lauren W; Sei, Janet J; Parekh, Nikhil J et al. (2015) Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection. J Virol 89:9974-85|
|Heipertz, Erica L; Davies, Michael L; Lin, Eugene et al. (2014) Prolonged antigen presentation following an acute virus infection requires direct and then cross-presentation. J Immunol 193:4169-77|
|Davies, Michael L; Sei, Janet J; Siciliano, Nicholas A et al. (2014) MyD88-dependent immunity to a natural model of vaccinia virus infection does not involve Toll-like receptor 2. J Virol 88:3557-67|
|Hersperger, Adam R; Siciliano, Nicholas A; DeHaven, Brian C et al. (2014) Epithelial immunization induces polyfunctional CD8+ T cells and optimal mousepox protection. J Virol 88:9472-5|
|Ma, Xueying; Xu, Ren-Huan; Roscoe, Felicia et al. (2013) The mature virion of ectromelia virus, a pathogenic poxvirus, is capable of intrahepatic spread and can serve as a target for delayed therapy. J Virol 87:7046-53|
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