Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization for infants and young children, but no vaccines or antiviral drugs are yet available. RSV infects the cells that line the nose, trachea and smaller airways. The overall goal of the laboratory is to understand how RSV infects its target cell, the ciliated airway cell, and to use that information to develop better vaccine and antiviral drug candidates. This laboratory uses primary well differentiated human airway epithelial cultures (HAECs) to study RSV infection. These HAECs have recently been used to identify an important RSV receptor on the ciliated airway cells. Preliminary data presented here demonstrate that the RSV produced by these HAECs is much more infectious for HAECs than for immortalized cells and its attachment, G, glycoprotein is responsible for this difference. The G protein is modified differently in HAECs as it passes through the cell, on its way to being incorporated into the RSV virion at the plasma membrane and this modification may be responsible for its enhanced activity. This project will identify the modification and the mechanism by which it is made. RSV also produces a secreted form of the G protein that triggers immune cells to migrate toward RSV-infected cells. This project will also determine if this secreted G protein is modified like the full-length version, and if its signaling activity is changed or enhanced by its modification, similar to the full-length G protein. Once the modification of the G protein and the secreted G protein are identified, and the mechanism by which they are modified are identified, this information could enable the production of more effective and economical live attenuated vaccines for RSV and provide targets for novel antiviral agents. This project will advance the NIH Mission of developing ?fundamental knowledge to extend healthy life and reduce the burdens of illness.?
Bronchiolitis and pneumonia in infants and young children are most commonly caused by respiratory syncytial virus (RSV). This project will explore a unique modification of the RSV attachment, G, glycoprotein, its role in enhancing infectivity and its effects on responding immune cells. The results could improve live attenuated vaccine candidates, provide novel targets for antiviral drugs, and provide a more realistic neutralization assay for antibodies against the G protein.!
|Grieves, Jessica L; Yin, Zhiwei; Garcia-Sastre, Adolfo et al. (2018) A viral-vectored RSV vaccine induces long-lived humoral immunity in cotton rats. Vaccine 36:3842-3852|
|Hicks, Stephanie N; Chaiwatpongsakorn, Supranee; Costello, Heather M et al. (2018) Five Residues in the Apical Loop of the Respiratory Syncytial Virus Fusion Protein F2 Subunit Are Critical for Its Fusion Activity. J Virol 92:|
|Mejias, Asuncion; Garcia-Maurino, Cristina; Rodriguez-Fernandez, Rosa et al. (2017) Development and clinical applications of novel antibodies for prevention and treatment of respiratory syncytial virus infection. Vaccine 35:496-502|
|Capella, Cristina; Chaiwatpongsakorn, Supranee; Gorrell, Erin et al. (2017) Prefusion F, Postfusion F, G Antibodies, and Disease Severity in Infants and Young Children With Acute Respiratory Syncytial Virus Infection. J Infect Dis 216:1398-1406|
|Corry, Jacqueline; Johnson, Sara M; Cornwell, Jessica et al. (2016) Preventing Cleavage of the Respiratory Syncytial Virus Attachment Protein in Vero Cells Rescues the Infectivity of Progeny Virus for Primary Human Airway Cultures. J Virol 90:1311-20|
|Johnson, Sara M; McNally, Beth A; Ioannidis, Ioannis et al. (2015) Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures. PLoS Pathog 11:e1005318|
|Ngwuta, Joan O; Chen, Man; Modjarrad, Kayvon et al. (2015) Prefusion F-specific antibodies determine the magnitude of RSV neutralizing activity in human sera. Sci Transl Med 7:309ra162|
|McGillivary, Glen; Jordan, Zachary B; Peeples, Mark E et al. (2013) Replication of respiratory syncytial virus is inhibited by the host defense molecule viperin. J Innate Immun 5:60-71|
|McLellan, Jason S; Ray, William C; Peeples, Mark E (2013) Structure and function of respiratory syncytial virus surface glycoproteins. Curr Top Microbiol Immunol 372:83-104|
|Lo, Michael K; Peeples, Mark E; Bellini, William J et al. (2012) Distinct and overlapping roles of Nipah virus P gene products in modulating the human endothelial cell antiviral response. PLoS One 7:e47790|
Showing the most recent 10 out of 12 publications