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PMID:21501828

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Citation

Morizono, K, Xie, Y, Olafsen, T, Lee, B, Dasgupta, A, Wu, AM and Chen, IS (2011) The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry. Cell Host Microbe 9:286-98

Abstract

Virus entry into cells is typically initiated by binding of virally encoded envelope proteins to specific cell surface receptors. Studying infectivity of lentivirus pseudotypes lacking envelope binding, we still observed high infectivity for some cell types. On further investigation, we discovered that this infectivity is conferred by the soluble bovine protein S in fetal calf serum, or Gas6, its human homolog. Gas6 enhances native infectivity of pseudotypes of multiple viral envelope proteins. Gas6 mediates binding of the virus to target cells by bridging virion envelope phosphatidylserine to Axl, a TAM receptor tyrosine kinase on target cells. Phagocytic clearance of apoptotic cells is known to involve bridging by Gas6. Replication of vaccinia virus, which was previously reported to use apoptotic mimicry to enter cells, is also enhanced by Gas6. These results reveal an alternative molecular mechanism of viral entry that can broaden host range and enhance infectivity of enveloped viruses.

Links

PubMed PMC3095825 Online version:10.1016/j.chom.2011.03.012

Keywords

Animals; Cell Membrane/metabolism; Cells, Cultured; Cricetinae; Humans; Intercellular Signaling Peptides and Proteins/metabolism; Phagocytosis/physiology; Phosphatidylserines/metabolism; Protein S/metabolism; Proto-Oncogene Proteins/metabolism; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Cell Surface; Sequence Homology, Amino Acid; Vaccinia virus/physiology; Viral Envelope Proteins/metabolism; Virus Attachment; Virus Internalization

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

BOVIN:ANXA5

enables

GO:0001786: phosphatidylserine binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GAS6

involved_in

GO:0019079: viral genome replication

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GAS6

involved_in

GO:0019064: fusion of virus membrane with host plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GAS6

involved_in

GO:0006909: phagocytosis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GAS6

enables

GO:0030674: protein-macromolecule adaptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GAS6

enables

GO:0001786: phosphatidylserine binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GAS6

involved_in

GO:0046813: receptor-mediated virion attachment to host cell

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GAS6

involved_in

GO:0046718: viral entry into host cell

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GAS6

involved_in

GO:0043277: apoptotic cell clearance

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UFO

enables

GO:0001786: phosphatidylserine binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:UFO

involved_in

GO:0006909: phagocytosis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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