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Mutagenesis of the RGD Motif in the Yellow Fever Virus 17D Envelope Protein

van der Most, Robbert G. and Corver, Jeroen and Strauss, James H. (1999) Mutagenesis of the RGD Motif in the Yellow Fever Virus 17D Envelope Protein. Virology, 265 (1). pp. 83-95. ISSN 0042-6822. doi:10.1006/viro.1999.0026.

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The envelope protein of yellow fever virus 17D (YFV-17D) contains a solvent-exposed RGD motif, which has led to the suggestion that integrins may function as cellular receptors for YFV-17D. We found that mutating the RGD motif to RGE had no effect on viral titers, whereas changing RGD to TGD, TGE, TAD, TAE, or RGS led to reduced titers. Substitution of RGD by RAD or RAE yielded RNA genomes that replicated in mammalian cells but could not spread to neighboring cells at 37°C. These mutants did spread through the cell monolayer at 30°C (both in mosquito cells and in SW13 cells) and viruses grown at this temperature were capable of infecting mammalian cells at 37°C. These results strongly suggest that RGD-mediated integrin binding does not play a major role in YFV-17D entry, since the RGD to RAD mutation, as well as many or all of the other mutations studied, should disrupt all RGD-dependent integrin binding. However, the RGD to RAD or RAE mutations (as well as TAD and TAE) severely destabilized the envelope protein at 37°C, providing an explanation for the observed phenotype. Implications of these findings are discussed in light of the fact that mutations that alter tropism or virulence in different flaviviruses are often found within the loop containing the RGD motif.

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Additional Information:© 1999 Academic Press. Received July 26, 1999; returned to author for revision August 19, 1999; accepted September 28, 1999. We thank Dr. Charles M. Rice for providing us with the anti-NS1 serum and the YFV plasmids pYF5939IV and pYFM5.2, Dr. Hiroaki Shizuya for providing us with the pBeloAC11 plasmid, Dr. Richard Kuhn for his help in designing Fig. 1, Edith Lenches for technical assistance, and Dr. Ilya Frolov for providing us with the helper plasmid tRNA-BBCD3. R.M. was supported by an EMBO postdoctoral fellowship (ALFT721-1994) and J.C. was supported by a postdoctoral fellowship from the Gosney Foundation. This work was supported by NIH Grant AI 20612.
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European Molecular Biology Organization (EMBO)ALFT721-1994
Gosney FoundationUNSPECIFIED
NIHAI 20612
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ID Code:63945
Deposited By: Donna Wrublewski
Deposited On:26 Jan 2016 18:56
Last Modified:10 Nov 2021 23:23

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