Identification of Mamu-DPA1, Mamu-DQA1, and Mamu-DRA alleles in a cohort of Chinese rhesus macaques.

Rhesus macaques have long been used as animal models for various human diseases; the susceptibility and/or resistance to some of these diseases are related to the major histocompatibility complex (MHC). To gain insight into the MHC background and to facilitate the experimental use of Chinese rhesus macaques, Mamu-DPA1, Mamu-DQA1, and Mamu-DRA alleles were investigated in 30 Chinese rhesus macaques by gene cloning and sequencing. A total of 14 Mamu-DPA1, 17 Mamu-DQA1, and 9 Mamu-DRA alleles were identified in this study. Of these alleles, 22 novel sequences have not been documented in earlier studies, including nine Mamu-DPA1, ten Mamu-DQA1, and three Mamu-DRA alleles. Interestingly, like Mafa-DQA1 and Mafa-DPA1, more than two Mamu-DQA1 and Mamu-DPA1 alleles were detected in one animal in this study, which suggested that they might represent gene duplication. If our findings can be validated by other studies, it will further increase the number of known Mamu-DPA1 and Mamu-DQA1 polymorphisms. Our data also indicated significant differences in MHC class II allele distribution among the Chinese rhesus macaques, Vietnamese cynomolgus macaques, and the previously reported rhesus macaques, which were mostly of Indian origin. This information will not only promote the understanding of Chinese rhesus macaque MHC diversity and polymorphism but will also facilitate the use of Chinese rhesus macaques in studies of human disease.

TRIM5α polymorphism identification in cynomolgus macaques of Vietnamese origin and Chinese rhesus macaques.

TRIM5α is a retroviral restriction factor, in which the B30.2 (SPRY) and coiled-coil domains cooperate to determine the specificity of TRIM5α-mediated capture of retroviral capsids. Here, all exons of TRIM5α were analyzed in 39 Vietnamese cynomolgus macaques (VCE) and 29 Chinese rhesus macaques (CR). Our results revealed the presence of 22 alleles using the PHASE 2.0 software package (PHylogenetics And Sequence Evolution), including two novel species-specific alleles with a low frequency in VCE in exons 4 and 8, which encoded the coiled-coil and B30.2 (SPRY) domains, respectively. Nine alleles were detected in both VCE and CR, while four alleles were likely shared between the species. Of these alleles, the highest frequencies of 38% and 26% occurred in VCE and CR, respectively. Importantly, we found that some alleles encoded the same coiled-coil domain, but not the SPRY domain. In contrast, other alleles encoded the same SPRY domain, but not the coiled-coil domain. Our findings will contribute to the understanding of the interaction between the two domains and the determination of the specificity of TRIM5α-mediated capture of retroviral capsids. Our results from the phylogenetic trees constructed for VCE and CR suggested that the macaques' ability to inhibit SIV replication became gradually stronger if they carried corresponding alleles in four clades (clades4-7). More interesting, in clade3, both novel allele pairs (4E100a, 10E147a) and allele pairs (7R17b and 13R11b), which had the strong ability to inhibit SIV replication, originated from the same ancestral allele, suggesting that the novel alleles might play a key role to determine an animal's ability to inhibit SIV/HIV replication. However, further studies are needed to increase our understanding of the genetic background of TRIM5α in these two macaque species.

Comprehensive identification of high-frequency and co-occurring Mafa-DPA1, Mafa-DQA1, Mafa-DRA, and Mafa-DOA alleles in Vietnamese cynomolgus macaques.

High-frequency alleles and/or co-occurring human leukocyte antigen alleles across loci appear to be more important than individual alleles as markers of disease risk and have clinical value as biomarkers for targeted screening or the development of new disease therapies. To better elucidate the major histocompatibility complex (MHC) background and to facilitate the experimental use of cynomolgus macaques, Mafa-DPA1, Mafa-DQA1, Mafa-DRA, and Mafa-DOA alleles were characterized, and their combinations were investigated in 30 Vietnamese macaques by gene cloning and sequencing. A total of 26 Mafa-DPA1, 18 Mafa-DQA1, 9 Mafa-DRA, and 15 Mafa-DOA alleles, including 7 high-frequency alleles, were identified in this study, respectively. In addition, 15 Mafa-DQA1, 17 Mafa-DPA1, 15 Mafa-DOA, and 2 Mafa-DRA alleles represented novel sequences that had not been documented in earlier studies. Our results also showed that the Vietnamese macaques might be valuable because no less than 30% of the test animals possessed Mafa-DRA*01:02:01 (90%), -DQA1*26:01:03 (37%), -DOA*01:02:07 (34%), and -DQA1*01:03:03 (30%). We previously reported that the combinations of MHC class II alleles, including the combination of DOA*01:02:07-DPA1*02:09 and DOA*01:02:07-DQA1*01:03:03, were detected in 17 and 14% of the animals, respectively. Interestingly, more than two Mafa-DQA1 and Mafa-DPA1 alleles were detected in one animal in this study, which suggested that they might be caused by a chromosomal duplication. If our findings can be validated by other studies, it will further enrich the number of known Mafa-DPA1 and Mafa-DQA1 polymorphisms. Our results identified the co-occurring MHC alleles across loci in a cohort of Vietnamese cynomolgus macaques, which emphasized the value of this species as a model for biomedical research.