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Journal of Virology, November 2007, p. 12169-12178, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.00835-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Lipid Raft Disruption by Cholesterol Depletion Enhances Influenza A Virus Budding from MDCK Cells{triangledown}

Subrata Barman and Debi P. Nayak*

Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095-1747

Received 18 April 2007/ Accepted 6 September 2007

Lipid rafts play critical roles in many aspects of the influenza A virus life cycle. Cholesterol is a critical structural component of lipid rafts, and depletion of cholesterol leads to disorganization of lipid raft microdomains. In this study, we have investigated the effect of cholesterol depletion by methyl-ß-cyclodextrin (MßCD) treatment on influenza virus budding. When virus-infected Madin-Darby canine kidney cells were treated with MßCD at the late phase of infection for a short duration, budding of virus particles, as determined by protein analysis and electron microscopy, increased with increasing concentrations and lengths of treatment. However, infectious virus yield varied, depending on the concentration and duration of MßCD treatment. Low concentrations of MßCD increased infectious virus yield throughout the treatment period, but higher concentrations caused an initial increase of infectious virus titer followed by a decrease with a longer duration. Relative infectivity of the released virus particles, on the other hand, decreased with increasing concentrations and durations of MßCD treatment. Loss of infectivity of virus particles is due to multiple effects of MßCD-mediated cholesterol depletion causing disruption of lipid rafts, changes in structural integrity of the viral membrane, leakage of viral proteins, a nick or hole on the viral envelope, and disruption of the virus structure. Exogenous cholesterol increased lipid raft integrity, inhibited particle release, and partially restored the infectivity of the released virus particles. These data show that disruption of lipid rafts by cholesterol depletion caused an enhancement of virus particle release from infected cells and a decrease in the infectivity of virus particles.

* Corresponding author. Mailing address: Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1747. Phone: (310) 825-8558. Fax: (310) 206-3865. E-mail: dnayak{at}ucla.edu

{triangledown} Published ahead of print on 12 September 2007.

Journal of Virology, November 2007, p. 12169-12178, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.00835-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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