Restriction of human immunodeficiency virus type 1 by TRIM-CypA occurs with rapid kinetics and independently of cytoplasmic bodies, ubiquitin, and proteasome activity

TRIM-CypA is an owl monkey-specific variant of the retrovirus restriction factor TRIM5alpha. Here, we exploit its modular domain organization and cyclosporine sensitivity to probe the kinetics and mechanism of TRIM5-mediated restriction. Time of addition/withdrawal experiments reveal that inhibition...

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Bibliographic Details
Published in:Journal of virology Vol. 79; no. 24; p. 15567
Main Authors: Perez-Caballero, David, Hatziioannou, Theodora, Zhang, Fengwen, Cowan, Simone, Bieniasz, Paul D
Format: Journal Article
Language:English
Published: United States 01.12.2005
Subjects:
Animals
Cytoplasm - metabolism
HIV-1 - genetics
HIV-1 - metabolism
Humans
Kinetics
Macaca mulatta
Proteasome Endopeptidase Complex - metabolism
Proteins - genetics
Proteins - metabolism
Ubiquitin - metabolism
Ubiquitin-Protein Ligases
ISSN:0022-538X
Online Access:Get more information
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Summary:TRIM-CypA is an owl monkey-specific variant of the retrovirus restriction factor TRIM5alpha. Here, we exploit its modular domain organization and cyclosporine sensitivity to probe the kinetics and mechanism of TRIM5-mediated restriction. Time of addition/withdrawal experiments reveal that inhibition of incoming human immunodeficiency virus type 1 capsids by TRIM-CypA occurs within minutes of their delivery to the target cell cytoplasm. However, while TRIM-CypA restriction is partly dependent on a RING domain, restriction occurs independently of the ubiquitin/proteasome system. Moreover, tagged TRIM-CypA proteins can be fully active as restriction factors without forming cytoplasmic bodies.
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ISSN:0022-538X
DOI:10.1128/JVI.79.24.15567-15572.2005