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A RhoA-derived peptide inhibits syncytium formation induced by respiratory syncytial virus and parainfluenza virus type 3

Nature Medicine volume 6, pages 35–40 (2000)Cite this article

Abstract

The fusion glycoproteins of human respiratory syncytial virus (RSV) and human parainfluenza virus type-3 (PIV-3) mediate virus entry and syncytium formation. Interaction between the fusion protein of RSV and RhoA, a small GTPase, facilitates virus-induced syncytium formation. We show here a RhoA-derived peptide inhibits RSV and syncytium formation induced by RSV and PIV-3, both in vitro by inhibition of cell-to-cell fusion and in vivo by reduction of peak titer by 2 log10 in RSV-infected mice. These findings indicate that the interaction between these two paramyxovirus fusion proteins and RhoA is an important target for new antiviral strategies.

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Figure 1: RhoA-derived peptide inhibits RSV infection and syncytium formation.
Figure 2: Effect of RhoA77-95 added after rgRSV infection.
Figure 3: Effect of RhoA-derived peptides on cell-to-cell fusion.
Figure 4: RhoA77-95 peptide competitively inhibits RhoA interaction with RSV F in an ELISA.
Figure 5: RhoA77-95 peptide treatment reduces illness and viral titers in RSV-infected mice.
Figure 6: Inhibition of PIV-3 infection by RhoA77-95 peptide.

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Acknowledgements

Rauf Kuli-Zade assisted with the animal experiments. M. Denison, V. Varthakavi and P. Wright did neutralization assays on coronavirus, herpes simplex virus type I and influenza virus, respectively. J. Exton, S. Aung and T. Johnson contributed through editorial comments and discussions. Fluorescent microscopy analyses were done in part through use of the Vanderbilt University Medical Center Cell Imaging Resource (supported by CA68485 and DK20593). This work was supported by National Institutes of Health grant RO1-AI-33933.

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Authors and Affiliations

  1. Department of Medicine, Vanderbilt University School of Medicine, Nashville, 37232, Tennessee, USA

    Manoj K. Pastey & Barney S. Graham

  2. Department of Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, 37232, Tennessee, USA

    Tara L. Gower, Paul W. Spearman, James E. Crowe Jr. & Barney S. Graham

  3. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, 37232, Tennessee, USA

    Paul W. Spearman & James E. Crowe Jr.

Authors
  1. Manoj K. Pastey
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  2. Tara L. Gower
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  3. Paul W. Spearman
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  4. James E. Crowe Jr.
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  5. Barney S. Graham
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Correspondence to Barney S. Graham.

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Pastey, M., Gower, T., Spearman, P. et al. A RhoA-derived peptide inhibits syncytium formation induced by respiratory syncytial virus and parainfluenza virus type 3. Nat Med 6, 35–40 (2000). https://doi.org/10.1038/71503

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