About this item:

140 Views | 179 Downloads

Author Notes:

Address correspondence to L. J. Anderson, larry.anderson@emory.edu.

Subjects:

Research Funding:

This work was supported by NIH grant 1U19AI095227 awarded to M.L.M. and L.J.A., NIH 1R01AI087798 (M.L.M.), and NIH R21 AI113385-01A1 (L.J.A. and A.G.O.); by funding from Children's Healthcare of Atlanta; by support from the immunology core and flow core of Emory Children's Pediatric Research Center; and by Emory Vaccinology Training Grant (VTP) T32 5T32AI074492-03.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Virology
  • CX3C motif
  • G proteins
  • live attenuated vaccines
  • respiratory syncytial virus
  • vaccines
  • virology
  • ATTACHMENT G GLYCOPROTEIN
  • CYSTEINE-RICH REGION
  • SOLUBLE G-PROTEIN
  • T-CELL RESPONSES
  • BALB/C MICE
  • MONOCLONAL-ANTIBODY
  • PULMONARY EOSINOPHILIA
  • VIRAL REPLICATION
  • EPITHELIAL-CELLS
  • YOUNG-CHILDREN

Mutating the CX3C Motif in the G Protein Should Make a Live Respiratory Syncytial Virus Vaccine Safer and More Effective

Show all authors Show less authors

Tools:

Journal Title:

Journal of Virology

Volume:

Volume 91, Number 10

Publisher:

, Pages e02059-16-e02059-16

Type of Work:

Article | Final Publisher PDF

Abstract:

Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif ( 182 CWAIC 186 ) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A 186 , within the CX3C motif, mutating it to CX4C ( 182 CWAIAC 187 ), which is known to block binding to CX3CR1, might decrease disease. We studied the effect of the CX4C mutation in two strains of RSV (A2 and r19F) in a mouse challenge model. We included RSV r19F because it induces mucus production and airway resistance, two manifestations of RSV infection in humans, in mice. Compared to wild-type (wt) virus, mice infected with CX4C had a 0.7 to 1.2 log 10 -fold lower virus titer in the lung at 5 days postinfection (p.i.) and had markedly reduced weight loss, pulmonary inflammatory cell infiltration, mucus production, and airway resistance after challenge. This decrease in disease was not dependent on decrease in virus replication but did correspond to a decrease in pulmonary Th2 and inflammatory cytokines. Mice infected with CX4C viruses also had higher antibody titers and a Th1-biased T cell memory response at 75 days p.i. These results suggest that the CX4C mutation in the G protein could improve the safety and efficacy of a live attenuated RSV vaccine.

Copyright information:

© 2017 American Society for Microbiology.

Export to EndNote