Diversity of TRIM5α and TRIMCyp sequences in cynomolgus macaques from different geographical origins
- 213 Downloads
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.
KeywordsCynomolgus Macaque TRIM5α TRIMCyp
We gratefully acknowledge the expert assistance of veterinary and support staff. We thank Sam Wilson for designing the oligonucleotides. This work was supported by the NIHR Centre for Research in Health Protection at the Health Protection Agency, grants G0600007 and G0801172 from the UK Medical Research Council, the UCL/UCLH National Institute of Health Research Comprehensive Biomedical Research Centre and senior fellowship no. 090940 from the Wellcome Trust to GJT.
- Burwitz BJ, Pendley CJ, Greene JM, Detmer AM, Lhost JJ, Karl JA, Piaskowski SM, Rudersdorf RA et al (2009) Mauritian cynomolgus macaques share two exceptionally common major histocompatibility complex class I alleles that restrict simian immunodeficiency virus-specific CD8+ T cells. J Virol 83:6011–6019PubMedCrossRefGoogle Scholar
- Florese RH, Wiseman RW, Venzon D, Karl JA, Demberg T, Larsen K, Flanary L, Kalyanaraman VS et al (2008) Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection. Vaccine 26:3312–3321PubMedCrossRefGoogle Scholar
- Giraldo-Vela JP, Rudersdorf R, Chung C, Qi Y, Wallace LT, Bimber B, Borchardt GJ, Fisk DL et al (2008) The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers. J Virol 82:859–870PubMedCrossRefGoogle Scholar
- Kawamoto Y, Kawamoto S, Matsubayashi K, Nozawa K, Watanabe T, Stanley MA, Perwitasari-Farajallah D (2008) Genetic diversity of longtail macaques (Macaca fascicularis) on the island of Mauritius: an assessment of nuclear and mitochondrial DNA polymorphisms. J Med Primatol 37:45–54PubMedGoogle Scholar
- Lim SY, Chan T, Gelman RS, Whitney JB, O’Brien KL, Barouch DH, Goldstein DB, Haynes BF et al (2010a) Contributions of Mamu-A*01 status and TRIM5 allele expression, but not CCL3L copy number variation, to the control of SIVmac251 replication in Indian-origin rhesus monkeys. PLoS Genet 6:e1000997PubMedCrossRefGoogle Scholar
- Loffredo JT, Bean AT, Beal DR, Leon EJ, May GE, Piaskowski SM, Furlott JR, Reed J et al (2008) Patterns of CD8+ immunodominance may influence the ability of Mamu-B*08-positive macaques to naturally control simian immunodeficiency virus SIVmac239 replication. J Virol 82:1723–1738PubMedCrossRefGoogle Scholar
- Mee ET, Badhan A, Karl JA, Wiseman RW, Cutler K, Knapp LA, Almond N, O’Connor DH et al (2009a) MHC haplotype frequencies in a UK breeding colony of Mauritian cynomolgus macaques mirror those found in a distinct population from the same geographic origin. J Med Primatol 38:1–14PubMedCrossRefGoogle Scholar
- Mitchell JL, Mee ET, Almond NM, Cutler K, Rose NJ (2011) Characterisation of MHC haplotypes in a breeding colony of Indonesian cynomolgus macaques reveals a high level of diversity. Immunogenetics. doi: 10.1007/s00251-011-0567-z
- Reynolds MR, Sacha JB, Weiler AM, Borchardt GJ, Glidden CE, Sheppard NC, Norante FA, Castrovinci PA et al (2011) TRIM5α genotype of Rhesus macaques affects acquisition of SIVsmE660 infection after repeated limiting-dose intrarectal challenge. J Virol 85:9637–9640. doi: 10.1128/JVI.05074-11 Google Scholar
- Sussman R,Tattersall I (1986) Distribution, abundance, and putative ecological strategy of Macaca fascicularis on the island of Mauritius, Southwestern Indian Ocean. Folia Primatologica 46:28–43Google Scholar