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Journal of Virology, December 2006, p. 12160-12170, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.00643-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Respiratory Syncytial Virus F Envelope Protein Associates with Lipid Rafts without a Requirement for Other Virus Proteins{triangledown}

Elisa H. Fleming,1 Andrey A. Kolokoltsov,1 Robert A. Davey,1 Joan E. Nichols,1,2 and Norbert J. Roberts Jr.1,2*

Department of Microbiology and Immunology,1 Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-04352

Received 30 March 2006/ Accepted 15 September 2006

Like many enveloped viruses, human respiratory syncytial virus (RSV) assembles at and buds from lipid rafts. Translocation of the envelope proteins to these membrane subdomains is essential for production of infectious virus, but the targeting mechanism is poorly understood and it is not known if other virus proteins are required. Here we demonstrate that F protein of RSV intrinsically targets to lipid rafts without a requirement for any other virus protein, including the SH and G envelope proteins. Recombinant virus deficient in SH and G but retaining F protein expression was used to demonstrate that F protein still localized in rafts in both A549 and HEp-2 cells. Expression of a recombinant F gene by use of plasmid vectors demonstrated that F contains its own targeting domain and localized to rafts in the absence of other virus proteins. The domain responsible for translocation was then mapped. Unlike most other virus envelope proteins, F is unusual since the target signal is not contained within the cytoplasmic domain nor did it involve fatty acid modified residues. Furthermore, exchange of the transmembrane domain with that of the vesicular stomatitis virus G protein, a nonraft protein, did not alter F protein raft localization. Taken together, these data suggest that domains present in the extracellular portion of the protein are responsible for lipid raft targeting of the RSV F protein.


* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-0435. Phone: (409) 747-0236. Fax: (409) 772-6527. E-mail: nroberts{at}utmb.edu.

{triangledown} Published ahead of print on 27 September 2006.


Journal of Virology, December 2006, p. 12160-12170, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.00643-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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