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Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host.

ABSTRACT: In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a C-terminal frameshift in the toll-like receptor-4 (TLR4) gene of C. atys, is associated with a blunted in vitro response to TLR-4 ligands. In addition, we found a major structural change in exons 3-4 of the immune-regulatory protein intercellular adhesion molecule 2 (ICAM-2); expression of this variant leads to reduced cell surface expression of ICAM-2. These data provide a resource for comparative genomic studies of HIV and/or SIV pathogenesis and may help to elucidate the mechanisms by which SIV-infected sooty mangabeys avoid AIDS.

SUBMITTER: Palesch D

PROVIDER: S-EPMC5843367 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host.

Palesch David D Bosinger Steven E SE Tharp Gregory K GK Vanderford Thomas H TH Paiardini Mirko M Chahroudi Ann A Johnson Zachary P ZP Kirchhoff Frank F Hahn Beatrice H BH Norgren Robert B RB Patel Nirav B NB Sodora Donald L DL Dawoud Reem A RA Stewart Caro-Beth CB Seepo Sara M SM Harris R Alan RA Liu Yue Y Raveendran Muthuswamy M Han Yi Y English Adam A Thomas Gregg W C GWC Hahn Matthew W MW Pipes Lenore L Mason Christopher E CE Muzny Donna M DM Gibbs Richard A RA Sauter Daniel D Worley Kim K Rogers Jeffrey J Silvestri Guido G

Nature 20180101 7686

In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors ...[more]

PMID: 29300007

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Project description:To explore the differences between the extreme SIV infection phenotypes, nonprogression (BEN: benign) to AIDS in sooty mangabeys (SMs) and progression to AIDS (MAL: malignant) in rhesus macaques (RMs), we performed an integrated dual positive-negative connectivity (DPNC) analysis of gene coexpression networks (GCN) based on publicly available big data sets in the GEO database of NCBI. The microarray-based gene expression data sets were generated, respectively, from the peripheral blood of SMs and RMs at several time points of SIV infection. Significant differences of GCN changes in DPNC values were observed in SIV-infected SMs and RMs. There are three groups of enriched genes or pathways (EGPs) that are associated with three SIV infection phenotypes (BEN+, MAL+ and mixed BEN+/MAL+). The MAL+ phenotype in SIV-infected RMs is specifically associated with eight EGPs, including the protein ubiquitin proteasome system, p53, granzyme A, gramzyme B, polo-like kinase, Glucocorticoid receptor, oxidative phosyphorylation and mitochondrial signaling. Mitochondrial (endosymbiotic) dysfunction is solely present in RMs. Specific BEN+ pattern changes in four EGPs are identified in SIV-infected SMs, including the pathways contributing to interferon signaling, BRCA1/DNA damage response, PKR/INF induction and LGALS8. There are three enriched pathways (PRR-activated IRF signaling, RIG1-like receptor and PRR pathway) contributing to the mixed (BEN+/MAL+) phenotypes of SIV infections in RMs and SMs, suggesting that these pathways play a dual role in the host defense against viral infections. Further analysis of Hub genes in these GCNs revealed that the genes LGALS8 and IL-17RA, which positively regulate the barrier function of the gut mucosa and the immune homeostasis with the gut microbiota (exosymbiosis), were significantly differentially expressed in RMs and SMs. Our data suggest that there exists an exo- (dysbiosis of the gut microbiota) and endo- (mitochondrial dysfunction) symbiotic imbalance (EESI) in HIV/SIV infections. Dissecting the mechanisms of the exo-endo symbiotic balance (EESB) that maintains immune homeostasis and the EESI problems in HIV/SIV infections may lead to a better understanding of the pathogenesis of AIDS and the development of novel interventions for the rational control of this disease.

Project description:AbstractPrimates understand the meaning of their own and other species' alarm calls, but little is known about how they acquire such knowledge. Here, we combined direct behavioural observations with playback experiments to investigate two key processes underlying vocal development: comprehension and usage. Especifically, we studied the development of con- and heterospecific alarm call recognition in free-ranging sooty mangabeys, Cercocebus atys, across three age groups: young juveniles (1-2y), old juveniles (3-4y) and adults (> 5y). We observed that, during natural predator encounters, juveniles alarm called to a significantly wider range of species than adults, with evidence of refinement during the first four years of life. In the experiments, we exposed subjects to leopard, eagle and snake alarm calls given by other group members or sympatric Diana monkeys. We found that young juveniles' locomotor and vocal responses were least appropriate and that they engaged in more social referencing (look at adults when hearing an alarm call) than older individuals, suggesting that vocal competence is obtained via social learning. In conclusion, our results suggest that alarm call comprehension is socially learned during the juvenile stage, with comprehension preceding appropriate usage but no difference between learning their own or other species' alarm calls.Significance statementUnder natural conditions, animals do not just interact with members of their own species, but usually operate in a network of associated species. However, ontogenetic research on primate communication frequently ignores this significant element. We studied the development of con- and heterospecific alarm call recognition in wild sooty mangabeys. We found that communicative competence was acquired during the juvenile stages, with alarm call comprehension learning preceding appropriate vocal usage and with no clear difference in learning of con- and heterospecific signals. We also found that, during early stages of life, social referencing, a proactive form of social learning, was key in the acquisition of competent alarm call behaviour. Our results show that primates equally learn to interpret alarm calls from their own and other species during their early stages of life and that this learning process is refined as the animals mature.Supplementary informationThe online version contains supplementary material available at 10.1007/s00265-023-03318-6.

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Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host.

Publications

Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host.

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