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Journal of Amino Acids
Volume 2012 (2012), Article ID 575180, 16 pages
Research Article

Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides

1Department of Veterinary Pathobiology, Texas A&M University, TVMC, College Station, TX 77843-4467, USA
2Molecular Diagnostics Texas Veterinary Medical Diagnostic Laboratory, College Station, TX 77843, USA
3Department of Pharmacology and Physiology, Texas A&M University, TVMC, College Station, TX 77843-4467, USA
4Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Diggs 056, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA

Received 8 July 2011; Accepted 16 November 2011

Academic Editor: Jordi Bella

Copyright © 2012 Megan E. Schroeder et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Rotavirus (RV) NSP4, the first described viral enterotoxin, is a multifunctional glycoprotein that contributes to viral pathogenesis, morphogenesis, and replication. NSP4 binds both termini of caveolin-1 and is isolated from caveolae fractions that are rich in anionic phospholipids and cholesterol. These interactions indicate that cholesterol/caveolin-1 plays a role in NSP4 transport to the cell surface, which is essential to its enterotoxic activity. Synthetic peptides were utilized to identify target(s) of intervention by exploring the NSP4-caveolin-1 and -cholesterol interactions. NSP4112–140 that overlaps the caveolin-1 binding domain and a cholesterol recognition amino acid consensus (CRAC) motif and both termini of caveolin-1 (N-caveolin-12–20,  19–40 and C-caveolin-1161–180) were synthesized. Direct fluorescence-binding assays were employed to determine binding affinities of the NSP4-caveolin-1 peptides and cholesterol. Intracellular cholesterol alteration revealed a redistribution of NSP4 and disintegration of viroplasms. These data further imply interruption of NSP4112–140-N-caveolin-119–40 and cholesterol interactions may block NSP4 intracellular transport, hence enterotoxicity.