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PMID:19036818

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Citation

Jouvenet, N, Neil, SJ, Zhadina, M, Zang, T, Kratovac, Z, Lee, Y, McNatt, M, Hatziioannou, T and Bieniasz, PD (2009) Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J. Virol. 83:1837-44

Abstract

The expression of many putative antiviral genes is upregulated when cells encounter type I interferon (IFN), but the actual mechanisms by which many IFN-induced gene products inhibit virus replication are poorly understood. A recently identified IFN-induced antiretroviral protein, termed tetherin (previously known as BST-2 or CD317), blocks the release of nascent human immunodeficiency virus type 1 (HIV-1) particles from infected cells, and an HIV-1 accessory protein, Vpu, acts as a viral antagonist of tetherin. Here, we show that tetherin is capable of blocking not only the release of HIV-1 particles but also the release of particles assembled using the major structural proteins of a variety of prototype retroviruses, including members of the alpharetrovirus, betaretrovirus, deltaretrovirus, lentivirus, and spumaretrovirus families. Moreover, we show that the release of particles assembled using filovirus matrix proteins from Marburg virus and Ebola virus is also sensitive to inhibition by tetherin. These findings indicate that tetherin is a broadly specific inhibitor of enveloped particle release, and therefore, inhibition is unlikely to require specific interactions with viral proteins. Nonetheless, tetherin colocalized with nascent virus-like particles generated by several retroviral and filoviral structural proteins, indicating that it is present at, or recruited to, sites of particle assembly. Overall, tetherin is potentially active against many enveloped viruses and likely to be an important component of the antiviral innate immune defense.

Links

PubMed PMC2643743 Online version:10.1128/JVI.02211-08

Keywords

Antigens, CD/pharmacology; Antiviral Agents/pharmacology; Cell Line; Filoviridae/drug effects; GPI-Linked Proteins; Humans; Membrane Glycoproteins/pharmacology; Retroviridae/drug effects

Significance

Annotations

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

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:0045087: innate immune response

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

See also

References

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