Sulfatide regulates caspase-3-independent apoptosis of influenza A virus through viral PB1-F2 protein
Influenza A virus (IAV) generally causes caspase-dependent apoptosis based on caspase-3 activation, resulting in nuclear export of newly synthesized viral nucleoprotein (NP) and elevated virus replication. Sulfatide, a sulfated galactosylsphingolipid, enhances IAV replication through promoting newly...
Saved in:
Published in | PloS one Vol. 8; no. 4; p. e61092 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
04.04.2013
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Influenza A virus (IAV) generally causes caspase-dependent apoptosis based on caspase-3 activation, resulting in nuclear export of newly synthesized viral nucleoprotein (NP) and elevated virus replication. Sulfatide, a sulfated galactosylsphingolipid, enhances IAV replication through promoting newly synthesized viral NP export induced by association of sulfatide with hemagglutinin delivered to the cell surface. Here, we demonstrated that sulfatide is involved in caspase-3-independent apoptosis initiated by the PB1-F2 protein of IAV by using genetically sulfatide-produced cells and PB1-F2-deficient IAVs. Sulfatide-deficient COS7 cells showed no virus-induced apoptosis, whereas SulCOS1 cells, sulfatide-enriched COS7 cells that genetically expressed the two transferases required for sulfatide synthesis from ceramide, showed an increase in IAV replication and were susceptible to caspase-3-independent apoptosis. Additionally, PB1-F2-deficient IAVs, which were generated by using a plasmid-based reverse genetics system from a genetic background of A/WSN/33 (H1N1), demonstrated that PB1-F2 contributed to caspase-3-independent apoptosis in IAV-infected SulCOS1 cells. Our results show that sulfatide plays a critical role in efficient IAV propagation via caspase-3-independent apoptosis initiated by the PB1-F2 protein. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: TT TS. Performed the experiments: TT MT TK. Analyzed the data: TT MT TK. Contributed reagents/materials/analysis tools: TT TS. Wrote the paper: TT TS. Competing Interests: The authors have declared that no competing interests exist. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0061092 |