Mutation of Respiratory Syncytial Virus G Protein's CX3C Motif Attenuates Infection in Cotton Rats and Primary Human Airway Epithelial Cells

• Type of Material: Article
• Authors: Ha Binh, Emory University; Tatiana Chirkova, Emory University; Marina S. Boukhvalova, Sigmovir Biosystems Inc.; He Sun, Emory University; Edward E. Walsh, University of Rochester; TJ Mariani, University of Rochester; Larry Anderson, Emory University; Christopher S. Anderson, University of Rochester
• Language: English
• Date: 2019-09-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/vaccines7030069
• Title of Journal or Parent Work: Vaccines
• ISSN: 2076-393X
• Volume: 7
• Issue: 3
• Grant/Funding Information: This research was funded by internal resources from Emory University; Children’s Healthcare of Atlanta; support from the Immunology Core and Flow core of Emory Children’s Pediatric Research Center; and NIH grant R21 AI113385-01A1 (Larry J. Anderson).
• Keywords: AGENT; RECOVERY; GLYCOPROTEIN MONOCLONAL-ANTIBODY; Research & Experimental Medicine; YOUNG-CHILDREN; RSV G protein; Life Sciences & Biomedicine; respiratory syncytial virus; INFANTS; live RSV vaccines; PULMONARY INFLAMMATION; DISEASE; BURDEN; Medicine, Research & Experimental; Immunology; VACCINE; Science & Technology; RSV
• Research Categories: Biology, Virology; Health Sciences, Medicine and Surgery

Abstract

Despite being a high priority for vaccine development, no vaccine is yet available for respiratory syncytial virus (RSV). A live virus vaccine is the primary type of vaccine being developed for young children. In this report, we describe our studies of infected cotton rats and primary human airway epithelial cells (pHAECs) using an RSV r19F with a mutation in the CX3C chemokine motif in the RSV G protein (CX4C). Through this CX3C motif, RSV binds to the corresponding chemokine receptor, CX3CR1, and this binding contributes to RSV infection of pHAECs and virus induced host responses that contribute to disease. In both the cotton rat and pHAECs, the CX4C mutation decreased virus replication and disease and/or host responses to infection. Thus, this mutation, or other mutations that block binding to CX3CR1, has the potential to improve a live attenuated RSV vaccine by attenuating both infection and disease pathogenesis.