Project Summary Viruses have evolved a vast array of mechanisms to avoid detection and/or elimination by host defenses and to establish persistent infections that not only ensures survival in the human population, but can also contribute to pathogenesis. While we have developed effective antiviral drugs and vaccines against some important viruses, the threat of viral diseases worldwide remains, largely due to antigenic drift and shift, drug resistant mutants, emerging infectious agents, and importantly persistent or latent infections. The complexity and diversity of persistence and pathogenesis mechanisms utilized by viruses pose major challenges to the development of effective vaccines and chemical or immune-based treatments of virus diseases. To address these complex problems, it is essential to understand the mechanisms underlying viral persistence and pathogenesis, at the molecular level. Thus, there continues to be an urgent need to train a new generation of independent investigators with the interdisciplinary experience and expertise to address the complex issues of viral persistence and pathogenesis. A goal of the training program has been, and will continue to be, the recruitment of undergraduates and recent Ph.D. graduates in related disciplines (biochemistry, biological sciences, cellular and molecular biology, etc) into advanced studies in mechanisms of viral persistence and pathogenesis. The training program brings together the expanding number of basic science faculty devoted to the study of viruses and translational research in the Department of Microbiology and Molecular Genetics, the Department of Pediatrics, the Cancer Virology Program, and the Center for Vaccine Research at the University of Pittsburgh School of Medicine, and the Graduate School of Public Health. The Viral Persistence and Pathogenesis (VPP) training program offers a unique opportunity for the coordinated interdisciplinary research training of predoctoral trainees within the structure of the Program in Microbiology and Immunology (PMI) and postdoctoral trainees within the laboratories of the VPP faculty, with additional training via specialized course offerings, dedicated research seminars, retreats, and participation in national scientific meetings. Importantly, the VPP program is unique in that it leverages concepts in persistence and pathogenesis from diverse viral systems with the goal of educating trainees of the diversity of mechanisms, but also enabling the utilization of common themes for their research. Support for 4 predoctoral and 2 postdoctoral trainees per year is requested. The VPP program remains committed to the need to increase diversity in trainees, to provide training in the responsible conduct of research, and to provide career guidance for trainees.