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Antimicrobial Agents and Chemotherapy, November 2003, p. 3470-3477, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3470-3477.2003

Antiviral Activity of RhoA-Derived Peptides against Respiratory Syncytial Virus Is Dependent on Formation of Peptide Dimers

Philip J. Budge,^1,2 Jacob Lebowitz,³ and Barney S. Graham^2*

Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232,¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases,² Molecular Interactions Resource, Division of Bioengineering and Physical Science, Office of Research Services, Office of the Director, National Institutes of Health, Bethesda, Maryland, 20892³

Received 12 February 2003/ Returned for modification 10 June 2003/ Accepted 22 July 2003

A synthetic peptide containing amino acids 77 to 95 of the intracellular GTPase RhoA has previously been shown to inhibit replication of respiratory syncytial virus (RSV) in cultured cells. We show that residues 80 to 90 of RhoA are sufficient for this activity and that the cysteine residue at position 83 is critical. Further studies with an optimal peptide sequence containing amino acids 80 to 94 of RhoA revealed that the antiviral potency of the peptide is dependent on the oxidation of cysteine 83. Size-exclusion chromatography and sedimentation equilibrium studies of the peptide comprising residues 80 to 94 revealed that it is capable of forming aggregates in both reduced and oxidized states. A peptide (83A) in which the cysteine residue is replaced by an alanine does not form dimers or higher-order aggregates and did not inhibit RSV replication at any concentration tested. These data indicate that formation of peptide multimers is necessary for the antiviral activities of RhoA-derived peptides and suggest that the observed antiviral activities of these peptides may be unrelated to the biological functions of their parent molecule.

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* Corresponding author. Mailing address: Vaccine Research Center-NIAID, National Institutes of Health, MSC 3017, Bldg. 40, Room 2502, 40 Convent Dr., Bethesda, MD 20892-3017. Phone: (301) 594-8468. Fax: (301) 480-2771. E-mail: bgraham{at}nih.gov.

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Antimicrobial Agents and Chemotherapy, November 2003, p. 3470-3477, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3470-3477.2003

This article has been cited by other articles:

• Budge, P. J., Graham, B. S. (2004). Inhibition of respiratory syncytial virus by RhoA-derived peptides: implications for the development of improved antiviral agents targeting heparin-binding viruses. J Antimicrob Chemother 54: 299-302 [Abstract] [Full Text]  
• Budge, P. J., Li, Y., Beeler, J. A., Graham, B. S. (2004). RhoA-Derived Peptide Dimers Share Mechanistic Properties with Other Polyanionic Inhibitors of Respiratory Syncytial Virus (RSV), Including Disruption of Viral Attachment and Dependence on RSV G. J. Virol. 78: 5015-5022 [Abstract] [Full Text]