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 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.
Perez-Caballero
David
D
Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA.
Hatziioannou
Theodora
T
Zhang
Fengwen
F
Cowan
Simone
S
Bieniasz
Paul D
PD
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008253:Macaca mulatta; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
D011506:Proteins; D025801:Ubiquitin; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex