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

Authors

Binh Ha, Pediatric Infectious Diseases, Emory University and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Tatiana Chirkova, Pediatric Infectious Diseases, Emory University and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Marina S. Boukhvalova, Sigmovir Biosystems, Inc. Rockville, MD 20850, USA.
He Ying Sun, Pediatric Infectious Diseases, Emory University and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Edward E. Walsh, Rochester Regional HealthFollow
Christopher S. Anderson, 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.
Thomas J. Mariani, 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.
Larry J. Anderson, Pediatric Infectious Diseases, Emory University and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.

Department

Medicine

Document Type

Article

Publication Title

Vaccines

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.

DOI

10.3390/vaccines7030069

Volume

7

Issue

3

Publication Date

7-19-2019

PubMed ID

31330970

Recommended Citation

Ha, B., Chirkova, T., Boukhvalova, M. S., Sun, H. Y., Walsh, E. E., Anderson, C. S., Mariani, T. J., & Anderson, L. J. (2019). Mutation of Respiratory Syncytial Virus G Protein's CX3C Motif Attenuates Infection in Cotton Rats and Primary Human Airway Epithelial Cells. Vaccines, 7 (3) https://doi.org/10.3390/vaccines7030069