Adenovirus inhibition by peptidomimetic integrin antagonists

Paul J. Hippenmeyer, Peter G. Ruminski, Joseph G. Rico, H. S.Sharon Lu, David W. Griggs

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Many viruses and bacterial pathogens are capable of exploiting host cell surface integrins during their replication cycles. The ligands for many integrins contain an arginine-glycine-aspartic acid (RGD) amino acid sequence that is essential for protein-protein interaction. Human adenovirus particles contain this sequence in the penton base protein, and previous studies support a role for this RGD in integrin-dependent internalization of the virus by the cell. As synthetic peptidomimetics of RGD have been shown in other experimental systems to be antagonists of the activities of specific integrins both in vitro and in vivo, we sought to determine whether these small molecules are antagonists of adenovirus infection. Such compounds inhibited viral infection of cultured cells with similar rank order potency to that determined in assays utilizing purified extracellular matrix proteins as integrin ligands. The maximal level of inhibition achieved with the peptidomimetics was comparable to that of RGD-containing peptides, whereas no significant effects were apparent with an RGE-containing peptide. An engineered adenovirus having a mutated RGD sequence in the penton base was not susceptible to the inhibition. The results obtained with these synthetic antagonists, which have varied structures and potencies, suggest that integrins interact with adenoviral RGD in a manner similar to that of other protein ligands such as vitronectin. Furthermore, the results confirm the role of RGD in the replication cycle, and suggest peptidomimetic compounds may be useful antimicrobial agents in the treatment of a variety of diseases.

Original languageEnglish
Pages (from-to)169-178
Number of pages10
JournalAntiviral Research
Volume55
Issue number1
DOIs
StatePublished - Jun 29 2002

Keywords

  • Adenovirus
  • Adhesion
  • Antiviral
  • Integrin
  • RGD

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