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Published on: February 12, 2018
Diversity of TRIM5α and TRIMCyp sequences in cynomolgus macaques from different geographical origins
Neil J Berry1, Flavia Marzetta, Greg J Towers
1Division of Retrovirology, National Institute for Biological Standards and Control, A Centre of the Health Protection Agency, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK.
Abstract:
The TRIM5α restriction factor can protect some species of monkeys, but not humans, from HIV infection. It has also emerged that some monkeys have a cyclophilin A domain retrotransposed into the TRIM5 locus resulting in the expression of a TRIMCyp protein with anti-retroviral activity. A high degree of sequence variation in the primate TRIM5 gene has been reported that varies between populations of rhesus macaques, a widely used non-human primate model of HIV/AIDS, and recently shown to correlate with susceptibility to simian immunodeficiency viruses in this species. Cynomolgus macaques are also used widely in HIV research. A non-indigenous population on Mauritius has highly restricted genetic diversity compared with macaques from Indonesia. The relative allelic diversity of TRIM5α and TRIMCyp within these two sub-populations may impact on the susceptibility of the macaques to simian immunodeficiency virus thereby influencing the outcome of studies using these monkeys. We sought to establish the genetic diversity of these alleles in cynomolgus macaques. We identified seven TRIM5α alleles in Indonesian macaques, three of which are novel, but only three in the Mauritian-origin macaques. Strikingly, 87% of Indonesian, but none of the Mauritian macaques, possessed a retrotransposed Cyp domain. A splice acceptor site single-nucleotide polymorphism that allows formation of a TRIMCyp protein was absent for the TRIM5α alleles found in the Mauritian macaques. The level of allelic diversity reported here is greater than previously proposed for cynomolgus macaque species.
Insights
Genetic diversity in cynomolgus macaque TRIM5 alleles varies significantly between Indonesian and Mauritian populations. This allelic variation, including TRIMCyp presence, impacts susceptibility to simian immunodeficiency virus.
Area of Science:
- Primate genetics
- Immunology
- Virology
Background:
- The TRIM5α restriction factor provides protection against HIV in some primates but not humans.
- TRIMCyp proteins, resulting from retrotransposed cyclophilin A domains, also exhibit anti-retroviral activity.
- TRIM5 gene variation in rhesus macaques correlates with susceptibility to simian immunodeficiency viruses (SIV).
Purpose of the Study:
- To investigate the genetic diversity of TRIM5α and TRIMCyp alleles in Indonesian and Mauritian cynomolgus macaques.
- To assess how this diversity may influence susceptibility to SIV.
- To compare genetic diversity between these two distinct cynomolgus macaque populations.
Main Methods:
- Sequencing of TRIM5α and associated regions in cynomolgus macaques from Indonesia and Mauritius.
- Identification and comparison of TRIM5α and TRIMCyp alleles between the two populations.
- Analysis of single-nucleotide polymorphisms related to TRIMCyp formation.
Main Results:
- Seven TRIM5α alleles were identified in Indonesian macaques (three novel), compared to only three in Mauritian macaques.
- 87% of Indonesian macaques possessed a retrotransposed cyclophilin A domain, forming TRIMCyp, while none of the Mauritian macaques did.
- A key single-nucleotide polymorphism for TRIMCyp formation was absent in Mauritian TRIM5α alleles.
- Allelic diversity in this study exceeded previous estimates for cynomolgus macaques.
Conclusions:
- Significant differences in TRIM5α and TRIMCyp allelic diversity exist between Indonesian and Mauritian cynomolgus macaques.
- The restricted genetic diversity and lack of TRIMCyp in Mauritian macaques may increase their susceptibility to SIV.
- These findings highlight the importance of macaque genetic background in SIV research and underscore the need for careful consideration of animal models.
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