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Journal of Virology, September 2008, p. 9245-9253, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00975-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Differential Cholesterol Binding by Class II Fusion Proteins Determines Membrane Fusion Properties{triangledown}

M. Umashankar, Claudia Sánchez-San Martín, Maofu Liao,{dagger} Brigid Reilly,{ddagger} Alice Guo,§ Gwen Taylor, and Margaret Kielian*

Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461

Received 9 May 2008/ Accepted 8 July 2008

The class II fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. These fusion proteins are triggered by low pH, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. Here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. Using cholesterol-depleted insect cells, we showed that fusion and infection by the alphaviruses Semliki Forest virus (SFV) and Sindbis virus were strongly promoted by cholesterol, with similar sterol dependence in laboratory and field isolates and in viruses passaged in tissue culture. The E1 fusion protein from SFV bound cholesterol, as detected by labeling with photocholesterol and by cholesterol extraction studies. In contrast, fusion and infection by numerous strains of the flavivirus dengue virus (DV) and by yellow fever virus 17D were cholesterol independent, and the DV fusion protein did not show significant cholesterol binding. SFV E1 is the first virus fusion protein demonstrated to directly bind cholesterol. Taken together, our results reveal important functional differences conferred by the cholesterol-binding properties of class II fusion proteins.

* Corresponding author. Mailing address: Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-3638. Fax: (718) 430-8574. E-mail: kielian{at}aecom.yu.edu

{triangledown} Published ahead of print on 16 July 2008.

{dagger} Present address: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA.

{ddagger} Present address: University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA.

§ Present address: Stony Brook University Medical Center, Stony Brook, NY.

Journal of Virology, September 2008, p. 9245-9253, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00975-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Haid, S., Pietschmann, T., Pecheur, E.-I. (2009). Low pH-dependent Hepatitis C Virus Membrane Fusion Depends on E2 Integrity, Target Lipid Composition, and Density of Virus Particles. J. Biol. Chem. 284: 17657-17667 [Abstract] [Full Text]  
  • Tong, J., Borbat, P. P., Freed, J. H., Shin, Y.-K. (2009). A scissors mechanism for stimulation of SNARE-mediated lipid mixing by cholesterol. Proc. Natl. Acad. Sci. USA 106: 5141-5146 [Abstract] [Full Text]  


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