Association of TRIMCyp and TRIM5α from assam macaques leads to a functional trade-off between HIV-1 and N-MLV inhibition
| Autor: | Yong-Tang Zheng, Jia-Wu Zhu, Dan Mu, Hong-Yi Zheng, Feng-Liang Liu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetic enhancement Ubiquitin-Protein Ligases Mutant Chimeric Proteins Gene Expression Biology General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Chimera (genetics) Cyclophilin A Mice RNA interference Gene expression Animals Humans Allele General Environmental Science Genetics 030102 biochemistry & molecular biology HEK 293 cells Proteins Leukemia Virus Murine 030104 developmental biology HEK293 Cells Cell culture Cats HIV-1 Leukocytes Mononuclear Macaca RNA Interference General Agricultural and Biological Sciences Retroviridae Infections |
| Zdroj: | Science China. Life sciences. 61(8) |
| ISSN: | 1869-1889 |
| Popis: | TRIM5α restricts retroviruses in a species-specific manner. Cyclophilin A was independently retrotransposed into the TRIM5 loci in different species, leading to the generation of antiviral TRIM5-cyclophilin A (TRIMCyp) proteins. Previously, we found that assam macaques express a TRIMCyp chimera (amTRIMCyp), along with a TRIM5α allelic protein (amTRIM5α). Herein, we investigated the antiviral activity of amTRIMCyp and amTRIM5α individually, as well as their interaction and joint effects. amTRIMCyp showed a divergent restriction pattern from amTRIM5α. Although both proteins potently restricted the replication of HIV-1, only amTRIM5α inhibited N-MLV. Remarkably, cellular anti-HIV-1 activity increased when amTRIMCyp and amTRIM5α were coexpressed, indicating a synergistic block of HIV-1 replication. Consistently, PMBCs from heterozygous amTRIM5α/TRIMCyp showed stronger resistance to HIV-1 infection than those from amTRIM5α/TRIM5α homozygotes. The anti-HIV-1 synergistic effect was dependent on the amTRIMCyp-amTRIM5α interaction. In contrast, amTRIMCyp completely abrogated the anti-N-MLV activity mediated by amTRIM5α, showing a dominant-negative effect, indicating that the generation of amTRIMCyp was involved in the trade-off between divergent restriction activities. Our results provide a new paradigm to study functional trade-offs mediated by allelic proteins, a theoretical basis for utilizing animal models with various TRIM5 alleles, as well as novel HIV-1 gene therapy strategies. |
| Databáze: | OpenAIRE |
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