MHC class I characterization of Indonesian cynomolgus macaques

Abstract

Cynomolgus macaques (Macaca fascicularis) are quickly becoming a useful model for infectious disease and transplantation research. Even though cynomolgus macaques from different geographic regions are used for these studies, there has been limited characterization of full-length Major Histocompatibility Complex (MHC) Class I immunogenetics of distinct geographic populations. Here, we identified 48 MHC class I cDNA nucleotide sequences in eleven Indonesian cynomolgus macaques, including 41 novel Mafa-A and Mafa-B sequences. We found seven MHC class I sequences in Indonesian macaques that were identical to MHC class I sequences identified in Malaysian or Mauritian macaques. Sharing of nucleotide sequences between these geographically distinct populations is also consistent with the hypothesis that Indonesia was a source of the Mauritian macaque population. In addition, we found that the Indonesian cDNA sequence Mafa-B*7601 is identical throughout its peptide binding domain to Mamu-B*03, an allele that has been associated with control of SIV viremia in Indian rhesus macaques. Overall, a better understanding of the MHC class I alleles present in Indonesian cynomolgus macaques improves their value as a model for disease research and it better defines the biogeography of cynomolgus macaques throughout Southeast Asia.

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing

“…1. Overall, the homologous duplications appear to be fewer in number in the Mafa-class I region (Campbell et al 2009;Otting et al 2007;Pendley et al 2008;Uda et al 2004;Watanabe et al 2007) than in the Mamu-class I region .…”

“…3.0. All of the Mafa-A, Mafa-B, and Mafa-I allele sequences were supported by conventional analytical methods, 56 were previously reported in IMGT/MHC-NHP database (Campbell et al 2009;Kita et al 2009;Krebs et al 2005;Lawrence et al 2012;Otting et al 2007;Pendley et al 2008;Uda et al 2004;Urvater et al 2000;Wiseman et al 2007;Wu et al 2008) and the other 56 (eight Mafa-A, 24 Mafa-B, six Mafa-I, 11…”

Animal models for HIV/AIDS research

“…For Chinese rhesus macaques, these differences probably reflect, at least to some extent, the incomplete adaptation of these viruses to this species owing to their passage history in Indian rhesus macaques. Comparisons of the MHC genes of cynomolgus macaques from multiple locations have revealed extraordinary sequence diversity among geographically distinct populations 103,104 . Furthermore, the TRIM5 genes of cynomolgus macaques are also the most diverse of any primate species characterized thus far, encoding polymorphisms in both the TRIM5α and TRIMCyp isoforms, including TRIMCyp proteins that differentially restrict HIV-1 (REF.…”

Multi-Low-Dose Mucosal Simian Immunodeficiency Virus SIVmac239 Challenge of Cynomolgus Macaques Immunized with “Hyperattenuated” SIV Constructs

“…Indeed, recent reports have demonstrated that both the H6 and H7 haplotypes in cynomolgus macaques from the Mauritius Island are associated with control and that the H5 haplotype is associated with poor outcome (16,48). Recent advances in the understanding of MHC organization in cynomolgus macaques of Indonesian and Philippines origin (11,54) have indicated much more genetically diverse MHC loci in these animals compared to animals of Mauritian origin. The potential impact of MHC haplotypes in cynomolgus macaques from the Philippines (used in this study), in regards to SIV resistance/susceptibility remains less well characterized (54).…”

“…Recent advances in the understanding of MHC organization in cynomolgus macaques of Indonesian and Philippines origin (11,54) have indicated much more genetically diverse MHC loci in these animals compared to animals of Mauritian origin. The potential impact of MHC haplotypes in cynomolgus macaques from the Philippines (used in this study), in regards to SIV resistance/susceptibility remains less well characterized (54). Following the initiation of the challenge phase, a subset of animals, independent of vaccination status, appeared relatively resistant to challenge, and in some instances required an escalating dose regimen to produce infection.…”