title: The ability of multimerized cyclophilin A to restrict retrovirus infection.
abstract: In owl monkeys, the typical retroviral restriction factor of primates, TRIM5alpha, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Javanbakht
authors.forename: Felipe
authors.initials: F
authors.lastname: Diaz-Griffero
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.forename: Darwin F
authors.initials: DF
authors.lastname: Yeung
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Byeongwoon
authors.initials: B
authors.lastname: Song
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016645:Aotidae; D036022:Capsid Proteins / Q000378:metabolism; D002460:Cell Line; D021984:Cyclophilin A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019281:Dimerization; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D036022:Capsid Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D021984:Cyclophilin A