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Published on: December 23, 2016
Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques
Kevin J Campbell1, Ann M Detmer, Julie A Karl
1Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53706, USA.
Abstract:
Cynomolgus macaques (Macaca fascicularis) provide increasingly common models for infectious disease research. Several geographically distinct populations of these macaques from Southeast Asia and the Indian Ocean island of Mauritius are available for pathogenesis studies. Though host genetics may profoundly impact results of such studies, similarities and differences between populations are often overlooked. In this study we identified 47 full-length MHC class I nucleotide sequences in 16 cynomolgus macaques of Filipino origin. The majority of MHC class I sequences characterized (39 of 47) were unique to this regional population. However, we discovered eight sequences with perfect identity and six sequences with close similarity to previously defined MHC class I sequences from other macaque populations. We identified two ancestral MHC haplotypes that appear to be shared between Filipino and Mauritian cynomolgus macaques, notably a Mafa-B haplotype that has previously been shown to protect Mauritian cynomolgus macaques against challenge with a simian/human immunodeficiency virus, SHIV(89.6P). We also identified a Filipino cynomolgus macaque MHC class I sequence for which the predicted protein sequence differs from Mamu-B*17 by a single amino acid. This is important because Mamu-B*17 is strongly associated with protection against simian immunodeficiency virus (SIV) challenge in Indian rhesus macaques. These findings have implications for the evolutionary history of Filipino cynomolgus macaques as well as for the use of this model in SIV/SHIV research protocols.
Insights
Filipino cynomolgus macaques possess unique MHC class I sequences, with some shared haplotypes offering potential protection against simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV). This genetic diversity impacts their use in infectious disease research.
Area of Science:
- Genetics and Immunology
- Primate Models in Research
Background:
- Cynomolgus macaques are vital models for infectious disease research, but genetic variations between populations are often overlooked.
- Host genetics significantly influence pathogenesis studies, necessitating a deeper understanding of macaque population genetics.
Purpose of the Study:
- To characterize the Major Histocompatibility Complex (MHC) class I nucleotide sequences in Filipino cynomolgus macaques.
- To compare these sequences with those from other macaque populations and assess implications for SIV/SHIV research.
Main Methods:
- Sequencing of 47 full-length MHC class I nucleotide sequences from 16 Filipino cynomolgus macaques.
- Bioinformatic analysis to identify unique and shared sequences and haplotypes.
Main Results:
- 39 of 47 MHC class I sequences were unique to the Filipino population.
- Identified two shared ancestral MHC haplotypes between Filipino and Mauritian macaques, including a protective Mafa-B haplotype.
- Discovered a Filipino MHC class I sequence differing by one amino acid from Mamu-B*17, associated with SIV protection.
Conclusions:
- Filipino cynomolgus macaques exhibit significant MHC class I genetic diversity.
- Shared haplotypes suggest evolutionary connections and potential for cross-population protection insights.
- Findings are crucial for optimizing the use of Filipino macaques in SIV/SHIV pathogenesis and vaccine research.
