| Title | Isolation of a peptide inhibitor of human rhinovirus. | ||
| Author | Poritz, Mark A; Malmstrom, Sharon; Schmitt, Amy; Kim, Marianne K-H; Zharkikh, Ludmilla; Kamb, Alexander; Teng, David H-F | ||
| Journal | Virology | Publication Year/Month | 2003-Aug |
| PMID | 12951031 | PMCID | -N/A- |
| Affiliation | 1.Deltagen Proteomics, Inc., 615 Arapeen Drive, Suite 300, Salt Lake City, UT 84108, USA. maporitz83@post.harvard.edu. | ||
Cell culture-based transdominant genetic techniques provide new methods for discovering peptide/RNA modulators of cellular pathways. We applied this technology to isolate a peptide inhibitor of human rhinovirus. A green fluorescent protein (GFP)-scaffolded library of cDNA fragments was expressed in HeLa cells from a retroviral vector and screened for inhibitors of rhinovirus-mediated cell killing. A DNA clone, I421, increased cell survival in an HRV14 challenge assay from less than 0.5% to greater than 60%. It encodes a 53-amino-acid C-terminal extension of the GFP scaffold. Particular subclones of Hela cells expressing I421 (exemplified by I421dp3) show a delay in virus production and a 50-fold decrease in viral RNA levels at 6-8 h postinfection. HRV2, HRV14, and HRV16 show a dramatic decrease in plaque-forming ability on I421dp3 while Coxsackievirus B3 showed a small reduction. Levels of ICAM-1, the receptor for the main rhinovirus serotype, are not altered in I421dp3.