GSBS Student Publications

Title

Integrity of membrane lipid rafts is necessary for the ordered assembly and release of infectious Newcastle disease virus particles

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Immunology and Virology; Department of Molecular Genetics and Microbiology

Date

10-17-2006

Document Type

Article

Medical Subject Headings

Animals; Cell Line; Cholesterol; Detergents; Kinetics; Membrane Microdomains; Microscopy, Electron; Newcastle disease virus; Viral Proteins; Virion; Virus Assembly; beta-Cyclodextrins

Disciplines

Immunology of Infectious Disease | Immunopathology | Life Sciences | Medicine and Health Sciences

Abstract

Membrane lipid raft domains are thought to be sites of assembly for many enveloped viruses. The roles of both classical lipid rafts and lipid rafts associated with the membrane cytoskeleton in the assembly of Newcastle disease virus (NDV) were investigated. The lipid raft-associated proteins caveolin-1, flotillin-2, and actin were incorporated into virions, while the non-lipid raft-associated transferrin receptor was excluded. Kinetic analyses of the distribution of viral proteins in lipid rafts, as defined by detergent-resistant membranes (DRMs), in non-lipid raft membranes, and in virions showed an accumulation of HN, F, and NP viral proteins in lipid rafts early after synthesis. Subsequently, these proteins exited the DRMs and were recovered quantitatively in purified virions, while levels of these proteins in detergent-soluble cell fractions remained relatively constant. Cholesterol depletion of infected cells drastically altered the association of viral proteins with DRMs and resulted in an enhanced release of virus particles with reduced infectivity. Decreased infectivity was not due to effects on subsequent virus entry, since the extraction of cholesterol from intact virus did not significantly reduce infectivity. Particles released from cholesterol-depleted cells had very heterogeneous densities and altered ratios of NP and glycoproteins, demonstrating structural abnormalities which potentially contributed to their lowered infectivity. Taken together, these results indicate that lipid rafts, including cytoskeleton-associated lipid rafts, are sites of NDV assembly and that these domains are important for ordered assembly and release of infectious Newcastle disease virus particles.

Rights and Permissions

Citation: J Virol. 2006 Nov;80(21):10652-62. Link to article on publisher's site

DOI of Published Version

10.1128/JVI.01183-06

Related Resources

Link to article in PubMed

Journal Title

Journal of virology

PubMed ID

17041223