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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Veröffentlicht in:Journal of virology Jg. 79; H. 24; S. 15567
Hauptverfasser: Perez-Caballero, David, Hatziioannou, Theodora, Zhang, Fengwen, Cowan, Simone, Bieniasz, Paul D
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.12.2005
Schlagworte:
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
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Abstract 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.
AbstractList 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.
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.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.
Author Zhang, Fengwen
Hatziioannou, Theodora
Bieniasz, Paul D
Perez-Caballero, David
Cowan, Simone
Author_xml – sequence: 1
  givenname: David
  surname: Perez-Caballero
  fullname: Perez-Caballero, David
  organization: Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA
– sequence: 2
  givenname: Theodora
  surname: Hatziioannou
  fullname: Hatziioannou, Theodora
– sequence: 3
  givenname: Fengwen
  surname: Zhang
  fullname: Zhang, Fengwen
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  givenname: Simone
  surname: Cowan
  fullname: Cowan, Simone
– sequence: 5
  givenname: Paul D
  surname: Bieniasz
  fullname: Bieniasz, Paul D
BackLink https://www.ncbi.nlm.nih.gov/pubmed/16306627$$D View this record in MEDLINE/PubMed
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Snippet TRIM-CypA is an owl monkey-specific variant of the retrovirus restriction factor TRIM5alpha. Here, we exploit its modular domain organization and cyclosporine...
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SubjectTerms 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
Title Restriction of human immunodeficiency virus type 1 by TRIM-CypA occurs with rapid kinetics and independently of cytoplasmic bodies, ubiquitin, and proteasome activity
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