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

Autor: Binh Ha, Tatiana Chirkova, Marina S. Boukhvalova, He Ying Sun, Edward E. Walsh, Christopher S. Anderson, Thomas J. Mariani, Larry J. Anderson
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Vaccines, Vol 7, Iss 3, p 69 (2019)
Druh dokumentu: article
ISSN: 2076-393X
DOI: 10.3390/vaccines7030069
Popis: 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.
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