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PMID:20943977

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Citation

Weidner, JM, Jiang, D, Pan, XB, Chang, J, Block, TM and Guo, JT (2010) Interferon-induced cell membrane proteins, IFITM3 and tetherin, inhibit vesicular stomatitis virus infection via distinct mechanisms. J. Virol. 84:12646-57

Abstract

Tetherin and IFITM3 are recently identified interferon-induced cellular proteins that restrict infections by retroviruses and filoviruses and of influenza virus and flaviviruses, respectively. In our efforts to further explore their antiviral activities against other viruses and determine their antiviral mechanisms, we found that the two antiviral proteins potently inhibit the infection of vesicular stomatitis virus (VSV), a prototype member of the Rhabdoviridae family. Taking advantage of this well-studied virus infection system, we show that although both tetherin and IFITM3 are plasma membrane proteins, tetherin inhibits virion particle release from infected cells, while IFITM3 disrupts an early event after endocytosis of virion particles but before primary transcription of incoming viral genomes. Furthermore, we demonstrate that both the N-terminal 21 amino acid residues and C-terminal transmembrane region of IFITM3 are required for its antiviral activity. Collectively, our work sheds light on the mechanisms by which tetherin and IFITM3 restrict infection with rhabdoviruses and possibly other pathogenic viruses.

Links

PubMed PMC3004348 Online version:10.1128/JVI.01328-10

Keywords

Antigens, CD/genetics; Antigens, CD/metabolism; Blotting, Northern; Blotting, Western; Cells, Cultured; Endocytosis; GPI-Linked Proteins/genetics; GPI-Linked Proteins/metabolism; Genome, Viral; Humans; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mutation/genetics; RNA, Messenger/genetics; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; Vesicular Stomatitis/genetics; Vesicular Stomatitis/prevention & control; Vesicular Stomatitis/virology; Vesicular stomatitis Indiana virus/pathogenicity; Virion/physiology; Virus Internalization; Virus Replication/physiology

Significance

Annotations

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

HUMAN:IFM3

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BST2

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BST2

involved_in

GO:1901253: negative regulation of intracellular transport of viral material

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BST2

involved_in

GO:0045071: negative regulation of viral genome replication

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BST2

part_of

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BST2

involved_in

GO:0009615: response to virus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFM2

involved_in

GO:0009615: response to virus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFM3

part_of

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:IFM3

involved_in

GO:0009615: response to virus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFM3

involved_in

GO:0032897: negative regulation of viral transcription

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFM3

involved_in

GO:0045071: negative regulation of viral genome replication

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFM3

involved_in

GO:0046597: negative regulation of viral entry into host cell

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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