Cynomolgus Macaques Of Vietnamese Origin Research Articles

MHC class I allele diversity in cynomolgus macaques of Vietnamese origin.

Cynomolgus macaques (Macaca fascicularis, Mafa) have been used as important experimental animal models for carrying out biomedical researches. The results of biomedical experiments strongly depend on the immunogenetic background of animals, especially on the diversity of major histocompatibility complex (MHC) alleles. However, there is much less information available on the polymorphism of MHC class I genes in cynomolgus macaques, than is currently available for humans. In this study, we have identified 40 Mafa-A and 60 Mafa-B exons 2 and 3 sequences from 30 unrelated cynomolgus macaques of Vietnamese origin. Among these alleles, 28 are novel. As for the remaining 72 known alleles, 15 alleles are shared with other cynomolgus macaque populations and 32 are identical to alleles previously reported in other macaque species. A potential recombination event was observed between Mafa-A1*091:02 and Mafa-A1*057:01. In addition, the Mafa-A1 genes were found to be more diverse than human HLA-A and the functional residues for peptide binding sites (PBS) or TCR binding sites (TBS) in Mafa-A1 have greater variability than that for non-PBS or non-TBS regions. Overall, this study provides important information on the diversity of Mafa-A and Mafa-B alleles from Vietnamese origin, which may help researchers to choose the most appropriate animals for their studies.

SAMHD1 Polymorphisms were Significantly Correlated with HIV/SIV Virus Load in PBMC from Chinese Rhesus Macaques and Cynomolgus Macaques.

Sterile alpha motif and histidine aspartate domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) is one of the novel restriction factors that potently supresses HIV-1 infection in myeloid cells at an early stage in the viral replication cycle. SAMHD1 activity is blocked by the action of viral accessory protein x (Vpx), which targets and recruits SAMHD1 for proteasomal degradation, in the SIVsm/HIV-2 lineage. The impact of SAMHD1 polymorphisms on viral replication in Chinese-origin rhesus macaques (CR) and cynomolgus macaques of Vietnamese origin (CM) have not been reported until now. Therefore, we aimed to explore the polymorphisms, as well as the impact of polymorphisms, on HIV- 2 and SIV infections among CR and CM. We found two variants, T168C and T320C, located in the SAM domain of CR SAMHD1, which were significantly correlated with the HIV-2ROD/SIVmac239 virus load, suggesting that T168C and T320C probably affected HIV-2ROD and anti-SIVmac239 replication in CR, respectively. Conversely, T320C possibly affected CM SAMHD1-mediated HIV-2ROD restriction. However, none of the variants were correlated with CM SAMHD1-mediated SIVmac239 restriction. Based on these results, we concluded that SAMHD1 polymorphisms did not affect SIVmac239 replication in CM, but perhaps altered HIV-2ROD infection; however, different sites of the SAM domain of SAMHD1 were responsible for restricting the replication of different viruses in CR.

Identification of five novel MHC class II alleles in cynomolgus macaques of Vietnamese origin.

We report here the identification of one Mafa-DPA1 and four Mafa-DQB1 novel alleles of Vietnamese cynomolgus macaques.

Ten novel MHC class II alleles identified in cynomolgus macaques of Vietnamese origin.

Five Mafa-DPB1, two Mafa-DQB1 and three Mafa-DRB novel alleles are identified in Vietnamese cynomolgus macaques.

Comprehensive identification of high-frequency and combination MHC-DMA and -DMB alleles in a cohort of Chinese rhesus macaques and cynomolgus macaques of Vietnamese origin

Rhesus and cynomolgus macaques are currently used as ideal animal models of immune response. Major histocompatibility complex (MHC) molecules play important roles in the susceptibility and/or resistance to many diseases. In this study, MHC-DMA and -DMB were first characterized by sequencing and cloning in 28 unrelated cynomolgus macaques from Vietnam and 34 unrelated Chinese rhesus macaques. A total of 23 novel alleles, including six high frequency alleles, were identified in this study. Our results showed that the alleles with the highest phenotypic frequencies were Mafa-DMA∗02:04:03 (57.1%), Mafa-DMB∗03:01:02 (76.9%), Mamu-DMA∗02:01:04 (88.2%), and Mamu-DMB∗03:02:02 (85%), respectively, indicating that distribution and frequencies of alleles had a few differences between Chinese rhesus macaques and cynomolgus macaques from Vietnam. Interestingly, compared to the cynomolgus macaques, we found that the combination of Mamu-DMA∗02:01:04-DMB∗03:02:02 was detected in 27 (79.4%) of 34 monkeys, suggesting that the combination of the MHC-DMA and -DMB alleles was probably a characteristic feature of the Chinese rhesus macaques. Our results will greatly increase the value of the two species as models for biomedical research.

Characterization of the major histocompatibility complex class IA alleles in cynomolgus macaques of Vietnamese origin

Cynomolgus macaques (Macaca fascicularis, Mafa) have emerged as an important animal model for infectious disease and transplantation research. Extensive characterization of their major histocompatibility complex (MHC) polymorphism regions therefore becomes urgently required. In this study, we identified 41 MHC class I A nucleotide sequences in 34 unrelated cynomolgus macaques of Vietnamese origin farmed in Southern China, including eight novel Mafa-A sequences. We found two sequences with perfect identity and six sequences with close similarity to previously defined MHC class I alleles from other populations, especially from Indonesian-origin macaques. We also found three Vietnamese-origin cynomolgus macaque MHC class I sequences for which the predicted protein sequences identical throughout their B and F binding pockets to Mamu-A1*001:01 and Mamu-A3*13:03, respectively. This is important because Mamu-A1*001:01 and Mamu-A3*13:03 are associated with longer survival and lower set-point viral load in simian immunodeficiency virus (SIV)-infected rhesus monkeys. These findings have implications for the evolutionary history of Vietnamese-origin cynomolgus macaque as well as for the use of this model in SIV/SHIV (a virus combining parts of the HIV and SIV genomes) research.

Comprehensive identification of high-frequency and co-occurring Mafa-B, Mafa-DQB1, and Mafa-DRB alleles in cynomolgus macaques of Vietnamese origin

High-frequency alleles and/or co-occurring human leukocyte antigen (HLA) alleles across loci appear to be more important than individual alleles, because they might be markers of disease risk that have clinical value as biomarkers for targeted screening or the development of new therapies. To better elucidate the major histocompatibility complex background and to facilitate the experimental use of cynomolgus macaques, Mafa-B, Mafa-DQB1, and Mafa-DRB alleles were characterized and their combinations were investigated from 30 macaques of Vietnamese origin by cloning and sequencing. A total of 48 Mafa-B, 22 Mafa-DQB1, and 42 Mafa-DRB alleles, were detected in this study, respectively. In addition, two Mafa-DQB1 and eight Mafa-DRB alleles represented novel sequences that had not been documented in earlier studies. Our results also showed that the macaque from Vietnam might be valuable because >30% of the test animals possessed Mafa-DRB*w304 (30%) and -DQB1*0616 (30%). We report that the combination of major histocompatibility complex (MHC) class I and II alleles, including the combination of DRB3*0403-DRB*w304, DRB1*1013-DRB*w304, and Mafa-B*007:01:01-DRB*w304, which was in 17%, 13%, and 13% of the animals, respectively. Interesting, more than two Mafa-DQB1 alleles detected in one animal in this study suggest that Mafa-DQB1, like Mafa-DRB, might be a duplication in the chromosome, which have ever been documented in cynomolgus monkeys but has not yet been observed in rhesus macaques or other primates. Our results for the high frequency of commonly co-occurring MHC alleles across loci in a cohort of the Vietnamese cynomolgus macaque emphasized the value of this species as a model for biomedical research.

Eighteen novel MHC class I A alleles identified in Vietnamese‐origin cynomolgus macaques

We report herein the identification of 18 novel Mafa-A alleles in cynomolgus macaques of Vietnamese origin.

Twenty‐three novel major histocompatibility complex class I B alleles identified in cynomolgus macaques of Vietnamese origin

We report herein the identification of 23 novel Mafa-B alleles in cynomolgus macaques of Vietnamese origin.

Characterization of the major histocompatibility complex class II DOB, DPB1, and DQB1 alleles in cynomolgus macaques of Vietnamese origin

Major histocompatibility complex (MHC) molecules play an important role in the susceptibility and/or resistance to many diseases. To gain an insight into the MHC background and to facilitate the experimental use of cynomolgus macaques, the second exon of the MhcMafa-DOB, -DPB1, and -DQB1 genes from 143 cynomolgus macaques were characterized by cloning to sequencing. A total of 16 Mafa-DOB, 16 Mafa-DPB1, and 34 Mafa-DQB1 alleles were identified, which revealed limited, moderate, and marked allelic polymorphism at DOB, DPB1, and DQB1, respectively, in a cohort of cynomolgus macaques of Vietnamese origin. In addition, 16 Mafa-DOB, 5 Mafa-DPB1, and 8 Mafa-DQB1 alleles represented novel sequences that had not been reported in earlier studies. Almost of the sequences detected at the DOB and DQB1 locus in the present study belonged to DOB*01 (100%) and DQB1*06 (62%) lineages, respectively. Interestingly, four, three, and one high-frequency alleles were detected at Mafa-DOB, -DPB1, and -DQB1, respectively, in this monkeys. The alleles with the highest frequency among these monkeys were Mafa-DOB*010102, Mafa-DPB1*13, and Mafa-DQB1*0616, and these were found in 33 (25.6%) of 129 monkeys, 32 (31.37%) of 102 monkeys, and 30 (31%) of 143 monkeys, respectively. The high-frequency alleles may represent high priority targets for additional characterization of immune function. We also carried out evolutionary and population analyses using these sequences to reveal population-specific alleles. This information will not only promote the understanding of MHC diversity and polymorphism in the cynomolgus macaque but will also increase the value of this species as a model for biomedical research.