Dataset Information

Novel MHC class I full-length allele and haplotype characterization in sooty mangabeys.

ABSTRACT: Sooty mangabeys (Cercocebus atys) are natural SIV hosts and the presumed source of HIV-2 and SIVmac, which makes them a valuable model for HIV/SIV research. However, like other African primates, little is known about their major histocompatibility complex (MHC) genetics. In this study, we used Roche/454 and Illumina MiSeq deep sequencing in order to determine the MHC class I transcripts in a cohort of 165 sooty mangabeys from the Yerkes National Primate Research Center (YNPRC). We have characterized 121 functionally full-length classical (Ceat-A and Ceat-B) and non-classical (Ceat-F and Ceat-I) alleles and have also identified 22 Ceat-A/Ceat-B haplotype chromosomal combinations. We correlated these Ceat-A/Ceat-B haplotype combinations to recently described microsatellite haplotypes from the YNPRC colony. These newly identified alleles and haplotypes establish a resource for studying cellular immunity in sooty mangabeys and provide a framework for rapidly cataloging MHC class I sequences in an understudied, yet important, nonhuman primate species.

SUBMITTER: Heimbruch KE

PROVIDER: S-EPMC4498956 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Novel MHC class I full-length allele and haplotype characterization in sooty mangabeys.

Heimbruch Katelyn E KE Karl Julie A JA Wiseman Roger W RW Dudley Dawn M DM Johnson Zach Z Kaur Amitinder A O'Connor David H DH

Immunogenetics 20150526 8

Sooty mangabeys (Cercocebus atys) are natural SIV hosts and the presumed source of HIV-2 and SIVmac, which makes them a valuable model for HIV/SIV research. However, like other African primates, little is known about their major histocompatibility complex (MHC) genetics. In this study, we used Roche/454 and Illumina MiSeq deep sequencing in order to determine the MHC class I transcripts in a cohort of 165 sooty mangabeys from the Yerkes National Primate Research Center (YNPRC). We have character ...[more]

PMID: 26009014

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Project description:AbstractIn many group-living animal species, interactions take place in changing social environments, increasing the information processing necessary to optimize social decision-making. Communities with different levels of spatial and temporal cohesion should differ in the predictability of association patterns. While the focus in this context has been on primate species with high fission-fusion dynamics, little is known about the variability of association patterns in species with large groups and high temporal cohesion, where group size and the environment create unstable subgroups. Here, we use sooty mangabeys as a model species to test predictability on two levels: on the subgroup level and on the dyadic level. Our results show that the entirety of group members surrounding an individual is close to random in sooty mangabeys; making it unlikely that individuals can predict the exact composition of bystanders for any interaction. At the same time, we found predictable dyadic associations based on assortative mixing by age, kinship, reproductive state in females, and dominance rank; potentially providing individuals with the ability to partially predict which dyads can be usually found together. These results indicate that animals living in large cohesive groups face different challenges from those with high fission-fusion dynamics, by having to adapt to fast-changing social contexts, while unable to predict who will be close-by in future interactions. At the same time, entropy measures on their own are unable to capture the predictability of association patterns in these groups.Significance statementWhile the challenges created by high fission-fusion dynamics in animal social systems and their impact on the evolution of cognitive abilities are relatively well understood, many species live in large groups without clear spatio-temporal subgrouping. Nonetheless, they show remarkable abilities in considering their immediate social environment when making social decisions. Measures of entropy of association patterns have recently been proposed to measure social complexity across species. Here, we evaluate suggested entropy measures in sooty mangabeys. The high entropy of their association patterns would indicate that subgroup composition is largely random, not allowing individuals to prepare for future social environments. However, the existence of strong assortativity on the dyadic level indicates that individuals can still partially predict who will be around whom, even if the overall audience composition might be unclear. Entropy alone, therefore, captures social complexity incompletely, especially in species facing fast-changing social environments.

Project description:In contrast to pathogenic HIV/SIV infections of humans and rhesus macaques (RMs), natural SIV infection of sooty mangabeys (SMs) is typically non-pathogenic despite high viremia. Several studies suggested that low immune activation and relative resistance of CD4+ central memory T-cells from virus infection are mechanisms that protect SMs from AIDS. In 2008 it was reported that plasmacytoid dendritic cells (pDCs) of SMs exhibit attenuated interferon-alpha (IFN-?) responses to TLR7/9 ligands in vitro, and that species-specific amino acid substitutions in SM Interferon Regulatory Factor-7 (IRF7) are responsible for this observation. Based on these findings, these authors proposed that "muted" IFN-? responses are responsible for the benign nature of SIV infection in SMs. However, other studies indicated that acutely SIV-infected SMs show robust IFN-? responses and marked upregulation of Interferon Stimulated Genes (ISGs). To investigate this apparent disparity, we first examined the role of the reported IRF7 amino acid substitutions in SMs. To this end, we sequenced all IRF7 exons in 16 breeders, and exons displaying variability (exons 2,3,5,6,7,8) in the remainder of the colony (177 animals). We found that the reported Ser-Gly substitution at position 191 was a sequencing error, and that several of the remaining substitutions represent only minor alleles. In addition, functional assays using recombinant SM IRF7 showed no defect in its ability to translocate in the nucleus and drive transcription from an IFN-? promoter. Furthermore, in vitro stimulation of SM peripheral blood mononuclear cells with either the TLR7 agonist CL097 or SIV(mac239) induced an 500-800-fold induction of IFN-? and IFN-? mRNA, and levels of IFN-? production by pDCs similar to those of RMs or humans. These data establish that IFN-? and IRF7 signaling in SMs are largely intact, with differences with RMs that are minor and unlikely to play any role in the AIDS resistance of SIV-infected SMs.

Dataset Information

Novel MHC class I full-length allele and haplotype characterization in sooty mangabeys.

Publications

Novel MHC class I full-length allele and haplotype characterization in sooty mangabeys.

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