title: The effect of exon 7 deletion during the evolution of TRIMCyp fusion proteins on viral restriction, cytoplasmic body formation and multimerization.
abstract: TRIMCyp is a fusion protein consisting of the TRIM5 gene product and retrotransposed Cyclophilin A (CypA). Two primate TRIMCyp fusion proteins with varying anti-HIV-1 activities independently evolved in owl monkeys and Old World monkeys. In addition, Old World monkey TRIMCyps lack exon7, which encodes amino acids in the Linker2 region. Previous studies on TRIM5α indicated that this region affects anti-retroviral activity, cytoplasmic body formation, and multimerization. The effects of exon7 deletion on the functions of the TRIMCyp are unclear. In this study, we found that the cytoplasmic bodies and multimers of owl monkey TRIMCyp (omTRIMCyp) are different from those of northern pig-tailed macaque TRIMCyp (npmTRIMCyp). In addition, we demonstrated that exon7 deletion affected cytoplasmic body formation and multimerization. Moreover, we unexpectedly found two chimeric proteins of omTRIMCyp and npmTRIMCyp that failed to block HIV-1 replication, despite the presence of CypA in omTRIMCyp. Further studies indicated that the cytoplasmic bodies and spontaneous multimerization were not responsible for TRIMCyp anti-HIV-1 activity. Moreover, potent viral restriction is associated with higher amounts of monomeric TRIMCyp when the CypA domain is able to recognize and bind to the HIV-1 capsid. Our results suggested that the deletion of exon7 during the evolution of TRIMCyp affected its function.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Feng Liang
authors.initials: FL
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Yi Qun
authors.initials: YQ
authors.lastname: Kuang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Mu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Hong Yi
authors.initials: HY
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Jia Wu
authors.initials: JW
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Yong Tang
authors.initials: YT
authors.lastname: Zheng
mesh_terms: D000818:Animals; D016645:Aotidae / Q000235:genetics / Q000821:virology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D002415:Cats; D002460:Cell Line; D021984:Cyclophilin A / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D003593:Cytoplasm / Q000235:genetics / Q000821:virology; D019143:Evolution, Molecular; D005091:Exons; D057809:HEK293 Cells; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D058507:Host Specificity; D006801:Humans; D008254:Macaca nemestrina / Q000235:genetics / Q000821:virology; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion; D014774:Virulence; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; D021984:Cyclophilin A
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