Journal
JOURNAL OF VIROLOGY
Volume 81, Issue 22, Pages 12169-12178Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00835-07
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Funding
- NIAID NIH HHS [AI16348, AI41681, R01 AI016348, R01 AI041681] Funding Source: Medline
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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-p-cyclodextrin (M beta CD) treatment on influenza virus budding. When virus-infected Madin-Darby canine kidney cells were treated with M beta CD 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 M beta CD treatment. Low concentrations of M beta CD 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 M beta CD treatment. Loss of infectivity of virus particles is due to multiple effects of M beta CD-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.
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