Exosomes are small vesicles that are released from donor cells and internalized by a recipient cell. These vesicles carry proteins, DNA and RNA. It is thought that they are important for cell-to-cell communication, and may be important for development of disease. Some viruses will use exosomes to spread infections. In other cases, exosomes from virus-infected cells can trigger anti-viral responses to help combat virus infections. Adenovirus is a virus that causes the common cold. The goal of this proposal is to examine how adenovirus infection alters the formation and composition of exosomes by comparing exosome formation in uninfected and infected cells in vitro. In addition, work will be performed to ask if there is a connection between altered exosome formation and severity of adenovirus infection. These studies will provide new information on the interaction between the host cell and viruses, and will lead to a greater understanding of exosome biogenesis and virus infections. This promotes the NSF mission because it promotes the progress of science. This project will also support the education of undergraduate and graduate students. Therefore, it fulfills the mission of the NSF to support education and diversity in science.<br/><br/>Exosome signaling pathways are likely to be an additional entry pathway for viruses as well as an additional mechanism by which viruses promote infection and pathogenesis. These proposed studies will evaluate how the common cold virus, adenovirus, affects the host organism via exosome biogenesis and composition in cell culture conditions and in animals. This proposal will focus on clarifying interactions between adenoviruses and exosomes. There are over 56 adenovirus serotypes infecting a variety of vertebrate and invertebrate species, making adenovirus a good virus model for this project. This proposal will test the hypothesis that exosome biogenesis, composition, and trafficking are altered by external factors/stimuli such as viral infections, thus leading to altered exosome biogenesis, composition, trafficking, and cellular uptake. The objectives to achieve the goal are: 1) to evaluate the in vitro impact of virus infection on exosome biogenesis, 2) to evaluate the in vitro impact of virus infection on exosome composition, 3) to evaluate the impact of exosomes on in vitro adenovirus infection, 4) to evaluate the in vivo impact of virus infection on exosome biogenesis. This proposal has high intellectual merit; the proposed research could significantly advance scientific knowledge in the field of virology and exosome biology. Broader impacts of this study include: 1) directly positioning the principal investigator to develop and sustain a new research program at Alabama State University and 2) training of under-represented undergraduate and graduate students in STEM fields.<br/><br/><br/><br/>This project is jointly funded by the Integrative Organismal Systems (IOS) Symbiosis and Self-Defense (SDS) program, the Established Program to Stimulate Competititve Research (EPSCoR),the Historically Black Colleges and Universities Undergraduate Program (HBCU-UP) and Historically Black Colleges and Universities Excellence in Research (HBCU-EiR) programs.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.