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The Effect of Exon 7 Deletion during the Evolution of TRIMCyp Fusion Proteins on Viral Restriction, Cytoplasmic Body Formation and Multimerization

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 encod...

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Autores principales: Liu, Feng Liang, Kuang, Yi Qun, Mu, Dan, Zheng, Hong Yi, Zhu, Jia Wu, Zheng, Yong Tang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378998/
https://www.ncbi.nlm.nih.gov/pubmed/25822622
http://dx.doi.org/10.1371/journal.pone.0121666
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author Liu, Feng Liang
Kuang, Yi Qun
Mu, Dan
Zheng, Hong Yi
Zhu, Jia Wu
Zheng, Yong Tang
author_facet Liu, Feng Liang
Kuang, Yi Qun
Mu, Dan
Zheng, Hong Yi
Zhu, Jia Wu
Zheng, Yong Tang
author_sort Liu, Feng Liang
collection PubMed
description 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.
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spelling pubmed-43789982015-04-09 The Effect of Exon 7 Deletion during the Evolution of TRIMCyp Fusion Proteins on Viral Restriction, Cytoplasmic Body Formation and Multimerization Liu, Feng Liang Kuang, Yi Qun Mu, Dan Zheng, Hong Yi Zhu, Jia Wu Zheng, Yong Tang PLoS One Research Article 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. Public Library of Science 2015-03-30 /pmc/articles/PMC4378998/ /pubmed/25822622 http://dx.doi.org/10.1371/journal.pone.0121666 Text en © 2015 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liu, Feng Liang
Kuang, Yi Qun
Mu, Dan
Zheng, Hong Yi
Zhu, Jia Wu
Zheng, Yong Tang
The Effect of Exon 7 Deletion during the Evolution of TRIMCyp Fusion Proteins on Viral Restriction, Cytoplasmic Body Formation and Multimerization
title The Effect of Exon 7 Deletion during the Evolution of TRIMCyp Fusion Proteins on Viral Restriction, Cytoplasmic Body Formation and Multimerization
title_full The Effect of Exon 7 Deletion during the Evolution of TRIMCyp Fusion Proteins on Viral Restriction, Cytoplasmic Body Formation and Multimerization
title_fullStr The Effect of Exon 7 Deletion during the Evolution of TRIMCyp Fusion Proteins on Viral Restriction, Cytoplasmic Body Formation and Multimerization
title_full_unstemmed The Effect of Exon 7 Deletion during the Evolution of TRIMCyp Fusion Proteins on Viral Restriction, Cytoplasmic Body Formation and Multimerization
title_short The Effect of Exon 7 Deletion during the Evolution of TRIMCyp Fusion Proteins on Viral Restriction, Cytoplasmic Body Formation and Multimerization
title_sort effect of exon 7 deletion during the evolution of trimcyp fusion proteins on viral restriction, cytoplasmic body formation and multimerization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378998/
https://www.ncbi.nlm.nih.gov/pubmed/25822622
http://dx.doi.org/10.1371/journal.pone.0121666
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