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Open AccessArticle

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

1
Pediatric Infectious Diseases, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
2
Sigmovir Biosystems, Inc. Rockville, MD 20850, USA
3
Department of Medicine, University of Rochester School of Medicine and Department of Medicine, Rochester General Hospital, Rochester, NY 14621, USA
4
Department of Neonatology, Program in Pediatric Molecular and Personalized Medicine, and Department of Microbiology and Immunology, University of Rochester School of Medicine, Rochester, NY 14642, USA
*
Author to whom correspondence should be addressed.
Vaccines 2019, 7(3), 69; https://doi.org/10.3390/vaccines7030069
Received: 28 May 2019 / Revised: 14 July 2019 / Accepted: 16 July 2019 / Published: 19 July 2019
(This article belongs to the Special Issue Vaccines for Respiratory Syncytial Virus)
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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. View Full-Text
Keywords: respiratory syncytial virus; live RSV vaccines; RSV G protein respiratory syncytial virus; live RSV vaccines; RSV G protein
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Ha, B.; Chirkova, T.; Boukhvalova, M.S.; Sun, H.Y.; Walsh, E.E.; Anderson, C.S.; Mariani, T.J.; Anderson, L.J. Mutation of Respiratory Syncytial Virus G Protein’s CX3C Motif Attenuates Infection in Cotton Rats and Primary Human Airway Epithelial Cells. Vaccines 2019, 7, 69.

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