Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1.
In owl monkeys, a retrotransposition event replaced the gene encoding the retroviral restriction factor TRIM5alpha with one encoding TRIMCyp, a fusion between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A. TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid protein. Here, we show that infection by retroviruses other than HIV-1 can be restricted by TRIMCyp, providing an explanation for the evolutionary retention of the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1 infection occurs before the earliest step of reverse transcription. TRIMCyp-mediated restriction involves at least two functions: (1) capsid binding, which occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil and cyclophilin A domains, and (2) an effector function that depends upon the B-box 2 domain.
Diaz-Griffero
Felipe
F
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Vandegraaff
Nick
N
Li
Yuan
Y
McGee-Estrada
Kathleen
K
Stremlau
Matthew
M
Welikala
Sohanya
S
Si
Zhihai
Z
Engelman
Alan
A
Sodroski
Joseph
J
D000818:Animals; D016645:Aotidae; D002213:Capsid / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D021984:Cyclophilin A / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; D021984:Cyclophilin A