BIOMEDICAL SCIENCES GRADUATE PROGRAM AUTUMN 2015

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1 THE OHIO STATE UNIVERSITY BIOMEDICAL SCIENCES GRADUATE PROGRAM AUTUMN 2015 Sara M. Johnson PhD Candidate Respiratory Syncytial Virus Uses CX3CR1 as a Cellular Receptor on Primary Human Airway Epithelial Cultures 23 September 2015 Graves :30 pm

2 VITA 23 July Born Akron, OH May B.S. Biology, Kent State University COMMITTEE MEMBERS Mark E. Peeples, Advisor Jianrong Li Douglas M. McCarty Stefan Niewiesk

3 ABSTRACT Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory disease in infants, but no vaccine or effective therapy is available. The initiation of RSV infection of immortalized cells is largely dependent on cell surface heparan sulfate (HS), a receptor for the RSV attachment (G) glycoprotein in immortalized cells. In primary well differentiated human airway epithelial (HAE) cultures, HS is not detectable on the apical surface of these cultures, including the ciliated cells that are the target cells for RSV. Here we show that soluble HS inhibits infection of immortalized cells, but not HAE cultures, confirming that HS is not the receptor on HAE cultures. Conversely, a nonneutralizing monoclonal antibody against the G protein that does not block RSV infection of immortalized cells, does inhibit infection of HAE cultures. This antibody was previously shown to block the interaction between the G protein and the chemokine receptor CX3CR1 and we have mapped the binding site for this antibody to the CX3C motif and its surrounding region in the G protein. We show that CX3CR1 is present on the apical surface of ciliated cells in HAE cultures. Infection of HAE cultures is reduced by an antibody against CX3CR1 and mutations in the G protein CX3C motif. Additionally, mice lacking CX3CR1 are less susceptible to RSV infection. These findings demonstrate that RSV uses CX3CR1 as a cellular receptor on HAE cultures and highlights the importance of using a physiologically relevant model to study virus entry and antibody neutralization.

4 RECENT ABSTRACTS AND PRESENTATIONS Johnson SM, Peeples ME Differential RSV neutralization on primary, well-differentiated human airway epithelial cells. Abstract for podium presentation. 9 th International Respiratory Syncytial Virus (RSV) Symposium, Cape Town, South Africa. Johnson SM, McNally BA, Ioannidis I, Flano E, Oomens AG, Partida-Sanchez S, Peeples ME Identification of CX3CR1 as a Cellular Receptor for Respiratory Syncytial Virus on Primary Well-Differentiated Human Airway Epithelial Cultures. Abstract for podium presentation. American Society for Virology 32 nd Annual Meeting, State College, PA. Johnson SM, McNally BA, Ioannidis I, Flano E, Partida-Sanchez S, Peeples ME CX3CR1 Is a Critical Cellular Receptor for RSV on Primary Well Differentiated Human Airway Epithelial Cultures. Abstract for poster presentation. 8 th International Respiratory Syncytial Virus (RSV) Symposium, Santa Fe, NM.

5 RECENT PUBLICATIONS Johnson SM, McNally BA, Ioannidis I, Flano E, Teng MN, Oomens AG, Walsh EE, Peeples ME (in press) Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures. PLoS Pathog Shelton CL, Raffel FK, Beatty WL, Johnson SM, Mason KM (2011) Sap Transporter Mediated Import and Subsequent Degradation of Antimicrobial Peptides in Haemophilus. PLoS Pathog 7(11): e doi: /journal.ppat

6 AWARDS AND HONORS Best oral presentation. 9 th International RSV Symposium. Stellenbosch, South Africa. November Academic enrichment award. The Research Institute at Nationwide Children s Hospital Annual Retreat. Columbus, OH. August Travel award. 9 th International RSV Symposium. Stellenbosch, South Africa. July Travel award. 13th Annual Wexner Medical Center Trainee Research Day. Columbus, OH. April Travel award. 8 th International RSV Symposium. Santa Fe, New Mexico. August FUTURE PLANS Upon graduation, I will continue an internship in the Office of Technology Commercialization at the Research Institute at Nationwide Children s Hospital. Following the internship, I plan to pursue a career in technology transfer.

7 [This must be the first line on Page 8] Biomedical Sciences Graduate Program 1170 Graves Hall 333 W. 10 th Avenue Columbus, Ohio