title: TRIMe7-CypA, an alternative splicing isoform of TRIMCyp in rhesus macaque, negatively modulates TRIM5α activity.
abstract: The existence of innate, host-specific restriction factors is a major obstacle to the development of nonhuman primate models for AIDS studies, and TRIM5α is one of the most important of these restriction factors. In recent years, a TRIM5 chimeric gene that was retrotransposed by a cyclophilin A (CypA) cDNA was identified in certain macaque species. The TRIM5α-CypA fusion protein, TRIMCyp, which was expressed in these monkeys, had lost its restriction ability toward HIV-1. We previously found that TRIMe7-CypA, an alternative splicing isoform of the TRIMCyp transcripts, was expressed in pig-tailed and rhesus macaques but absent in long-tailed macaques. In this study, the anti-HIV-1 activity of TRIMe7-CypA in the rhesus macaque (RhTRIMe7-CypA) was investigated. The over-expression of RhTRIMe7-CypA in CrFK, HeLa and HEK293T cells did not restrict the infection or replication of an HIV-1-GFP reporter virus in these cells. As a positive control, rhesus (rh)TRIM5α strongly inhibited the reporter virus. Intriguingly, the anti-HIV-1 activity of RhTRIM5α was significantly reduced in a dose-dependent manner by the co-repression of RhTRIMe7-CypA. Our data indicate that although the RhTRIMe7-CypA isoform does not appear to restrict HIV-1, it may act as a negative modulator of TRIM family proteins, presumably by competitive inhibition.
authors.affiliation: Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Na
authors.affiliation: Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001, China; Biotechnology Institute of Southern Medical University, Guangzhou 510515, China.
authors.forename: Yan-Dong
authors.initials: YD
authors.lastname: Tang
authors.affiliation: Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Liu
authors.affiliation: Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Yu
authors.affiliation: Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Liu-Ke
authors.initials: LK
authors.lastname: Sun
authors.affiliation: Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Yue-Zhi
authors.initials: YZ
authors.lastname: Lin
authors.affiliation: Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001, China. Electronic address: xjw@hvri.ac.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001, China; Harbin Pharmaceutical Group Biovaccine Company, Harbin 150069, China. Electronic address: jianhua_uc@126.com.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1; D008253:Macaca mulatta; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: D020033:Protein Isoforms; D011506:Proteins; D022821:RNA Splice Sites; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases
keywords: Splicing isoform; TRIMCyp; TRIMe7-CypA