TRIM5alpha association with cytoplasmic bodies is not required for antiretroviral activity.
The tripartite motif (TRIM) protein, TRIM5alpha, restricts infection by particular retroviruses. Many TRIM proteins form cytoplasmic bodies of unknown function. We investigated the relationship between cytoplasmic body formation and the structure and antiretroviral activity of TRIM5alpha. In addition to diffuse cytoplasmic staining, the TRIM5alpha proteins from several primate species were located in cytoplasmic bodies of different sizes; by contrast, TRIM5alpha from spider monkeys did not form cytoplasmic bodies. Despite these differences, all of the TRIM5alpha proteins exhibited the ability to restrict infection by particular retroviruses. Treatment of cells with geldanamycin, an Hsp90 inhibitor, resulted in disappearance or reduction of the TRIM5alpha-associated cytoplasmic bodies, yet exerted little effect on the restriction of retroviral infection. Studies of green fluorescent protein-TRIM5alpha fusion proteins indicated that no TRIM5alpha domain is specifically required for association with cytoplasmic bodies. Apparently, the formation of cytoplasmic bodies is not required for the antiretroviral activity of TRIM5alpha.
Song
Byeongwoon
B
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
Diaz-Griffero
Felipe
F
Park
Do Hyun
DH
Rogers
Thomas
T
Stremlau
Matthew
M
Sodroski
Joseph
J
D000818:Animals; D044966:Anti-Retroviral Agents / Q000378:metabolism*; D000090103:Antiviral Restriction Factors; D001483:Base Sequence; D016227:Benzoquinones; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002427:Cebidae; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004274:DNA, Recombinant / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006367:HeLa Cells; D006801:Humans; D047029:Lactams, Macrocyclic; D008253:Macaca mulatta; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012453:Saimiri; D013045:Species Specificity; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D044966:Anti-Retroviral Agents; D000090103:Antiviral Restriction Factors; D016227:Benzoquinones; D002352:Carrier Proteins; D004274:DNA, Recombinant; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011506:Proteins; D011809:Quinones; D011993:Recombinant Fusion Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; C001277:geldanamycin