title: Entry of Bluetongue Virus Capsid Requires the Late Endosome-specific Lipid Lysobisphosphatidic Acid.
abstract: The entry of viruses into host cells is one of the key processes of infection. The mechanisms of cellular entry for enveloped virus have been well studied. The fusion proteins as well as the facilitating cellular lipid factors involved in the viral fusion entry process have been well characterized. The process of non-enveloped virus cell entry, in comparison, remains poorly defined, particularly for large complex capsid viruses of the family Reoviridae, which comprises a range of mammalian pathogens. These viruses enter cells without the aid of a limiting membrane and thus cannot fuse with host cell membranes to enter cells. Instead, these viruses are believed to penetrate membranes of the host cell during endocytosis. However, the molecular mechanism of this process is largely undefined. Here we show, utilizing an in vitro liposome penetration assay and cell biology, that bluetongue virus (BTV), an archetypal member of the Reoviridae, utilizes the late endosome-specific lipid lysobisphosphatidic acid for productive membrane penetration and viral entry. Further, we provide preliminary evidence that lipid lysobisphosphatidic acid facilitates pore expansion during membrane penetration, suggesting a mechanism for lipid factor requirement of BTV. This finding indicates that despite the lack of a membrane envelope, the entry process of BTV is similar in specific lipid requirements to enveloped viruses that enter cells through the late endosome. These results are the first, to our knowledge, to demonstrate that a large non-enveloped virus of the Reoviridae has specific lipid requirements for membrane penetration and host cell entry.
authors.affiliation: From the Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: Avnish
authors.initials: A
authors.lastname: Patel
authors.affiliation: From the Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: Bjorn-Patrick
authors.initials: BP
authors.lastname: Mohl
authors.affiliation: From the Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom polly.roy@lshtm.ac.uk.
authors.forename: Polly
authors.initials: P
authors.lastname: Roy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001820:Bluetongue virus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism* / Q000821:virology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D018613:Microscopy, Confocal; D050178:Monoglycerides / Q000378:metabolism*; D009154:Mutation; D061987:Sf9 Cells; D018411:Spodoptera; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D008081:Liposomes; D008246:Lysophospholipids; D050178:Monoglycerides; C012786:bis(monoacylglyceryl)phosphate
keywords: bluetongue virus; endosome; lipid vesicle; lipid-protein interaction; lysobisphosphatidic acid; lysophospholipid; membrane; virus; virus entry