Lipid raft microdomains: key sites for Coxsackievirus A9 infectious cycle.
Lipid rafts have an important property to preferentially concentrate some proteins, while excluding others. Lipid rafts can also act as functional platforms for multiple signalling and trafficking processes. Several reports have shown that lipid rafts play a crucial role in the assembly of several enveloped viruses and possibly their cell entry. In this study we investigated the importance of lipid raft formation in Coxsackievirus A9 (CAV-9) entry and cell infection. Here by using a variety of biochemical and biophysical methods, we report that receptor molecules integrin alphavbeta3 and GRP78, which are implicated in CAV-9 infection as well as accessory molecules such as MHC class I, are accumulated in increased concentrations in lipid rafts following CAV-9 infection. In addition our studies revealed that raft integrity is essential for this virus since CAV-9 activates the Raf/MAPK signalling pathway within the raft and raft-disrupting drugs such as nystatin and MCD can successfully inhibit CAV-9 infection.
Triantafilou
Kathy
K
University of Portsmouth, Institute of Biomedical and Biomolecular Sciences, School of Biological Sciences, King Henry Building, King Henry I Street, Portsmouth, Hants, PO1 2DY, UK.
Triantafilou
Martha
M
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D000091342:Endoplasmic Reticulum Chaperone BiP; D029822:Enterovirus B, Human / Q000378:metabolism / Q000472:pathogenicity*; D031541:Fluorescence Resonance Energy Transfer; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism / Q000821:virology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D015398:Signal Transduction
D000091342:Endoplasmic Reticulum Chaperone BiP; C467732:GRP8 protein, human; C000717247:HSPA5 protein, human; D015395:Histocompatibility Antigens Class I; D039302:Integrin alphaVbeta3; D018013:Receptors, Neuropeptide; D019908:Proto-Oncogene Proteins c-raf; D020929:Mitogen-Activated Protein Kinase Kinases