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Author Notes:

Correspondence: ratripp@uga.edu; Tel.: +1-706-542-1557

A.B. and J.L.H. designed and performed experiments.

L.J.A. and L.M.H. helped analyze data.

A.B., J.L.H. and R.A.T. wrote the manuscript.

All authors read and approved manuscript.

We would like to thank Don Latner at the Centers for Disease Control and Prevention for providing reagents for the immunofluorescence assays.

We thank Peter Collins (National Institute of Allergy and Infectious Diseases, NIAID) for the use of the RSV reverse genetics system.

The authors declare no conflict of interest.

The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Subjects:

Keywords:

  • CX3CR1
  • IFNλ
  • RSV
  • microRNAs
  • respiratory syncytial virus

The central conserved region (CCR) of respiratory syncytial virus (RSV) G protein modulates host miRNA expression and alters the cellular response to infection

Tools:

Journal Title:

Vaccines

Volume:

Volume 5, Number 3

Publisher:

Type of Work:

Article | Final Publisher PDF

Abstract:

Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182–186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting.

Copyright information:

© 2017 by the authors. Licensee MDPI, Basel, Switzerland.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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