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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
- Source :
- PLoS ONE, Vol 10, Iss 3, p e0121666 (2015), PLoS ONE
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
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.
- Subjects :
- Cytoplasm
Recombinant Fusion Proteins
lcsh:Medicine
Cypa
Old World monkey
Biology
Virus Replication
Host Specificity
Cell Line
Evolution, Molecular
Cyclophilin A
Exon
Animals
Humans
lcsh:Science
Sequence Deletion
Genetics
Multidisciplinary
Virulence
Virus Assembly
lcsh:R
Exons
biology.organism_classification
Fusion protein
HEK293 Cells
Capsid
Viral replication
Cats
HIV-1
Aotidae
lcsh:Q
Macaca nemestrina
Protein Multimerization
Carrier Proteins
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....a6a488132b05d2de76c4100914e50992