How mangabey molar form differs under routine vs. fallback hard-object feeding regimes.

Background: Components of diet known as fallback foods are argued to be critical in shaping primate dental anatomy. Such foods of low(er) nutritional quality are often non-preferred, mechanically challenging resources that species resort to during ecological crunch periods. An oft-cited example of the importance of dietary fallbacks in shaping primate anatomy is the grey-cheeked mangabey Lophocebus albigena. This species relies upon hard seeds only when softer, preferred resources are not available, a fact which has been linked to its thick dental enamel. Another mangabey species with thick enamel, the sooty mangabey Cercocebus atys, processes a mechanically challenging food year-round. That the two mangabey species are both thickly-enameled suggests that both fallback and routine consumption of hard foods are associated with the same anatomical feature, complicating interpretations of thick enamel in the fossil record. We anticipated that aspects of enamel other than its thickness might differ between Cercocebus atys and Lophocebus albigena. We hypothesized that to function adequately under a dietary regime of routine hard-object feeding, the molars of Cercocebus atys would be more fracture and wear resistant than those of Lophocebus albigena. Methods: Here we investigated critical fracture loads, nanomechanical properties of enamel, and enamel decussation in Cercocebus atys and Lophocebus albigena. Molars of Cercopithecus, a genus not associated with hard-object feeding, were included for comparison. Critical loads were estimated using measurements from 2D µCT slices of upper and lower molars. Nanomechanical properties (by nanoindentation) and decussation of enamel prisms (by SEM-imaging) in trigon basins of one upper second molar per taxon were compared. Results: Protocone and protoconid critical fracture loads were significantly greater in Cercocebus atys than Lophocebus albigena and greater in both than in Cercopithecus. Elastic modulus, hardness, and elasticity index in most regions of the crown were greater in Cercocebus atys than in the other two taxa, with the greatest difference in the outer enamel. All taxa had decussated enamel, but that of Cercocebus atys uniquely exhibited a bundle of transversely oriented prisms cervical to the radial enamel. Quantitative comparison of in-plane and out-of-plane prism angles suggests that decussation in trigon basin enamel is more complex in Cercocebus atys than it is in either Lophocebus albigena or Cercopithecus cephus. These findings suggest that Cercocebus atys molars are more fracture and wear resistant than those of Lophocebus albigena and Cercopithecus. Recognition of these differences between Cercocebus atys and Lophocebus albigena molars sharpens our understanding of associations between hard-object feeding and dental anatomy under conditions of routine vs. fallback hard-object feeding and provides a basis for dietary inference in fossil primates, including hominins.

Impact of dominance rank specification in dyadic interaction models.

Dominance rank is a vital descriptor of social dynamics in animal societies and regularly used in studies to explain observed interaction patterns. However, researchers can choose between different indices and standardizations, and can specify dyadic rank relations differently when studying interaction distributions. These researcher degrees of freedom potentially introduce biases into studies and reduce replicability. Here, I demonstrate the impact of researcher choices by comparing the performance of different combinations of rank index, standardization, and model specification when explaining dyadic interaction patterns in sooty mangabeys (Cercocebus atys atys). I show that while no combination consistently performed best across interaction types (aggression, grooming, proximity, supplants), model specifications allowing for nonlinear patterns performed better than other models on average. Choices made in pre-processing and model building impacted model performance and subsequent interpretation of results. Researchers could end up describing social systems differently based on the same data. These results highlight the impact of researcher choices in the processing of behavioural data and potential limitations when using indirect species comparisons in animal behaviour research. To increase repeatability, researchers could make the impact of their processing choices more transparent and report results using a variety of indices and model specifications.

Familiarity modulates both intra- and interspecific yawn contagion in red-capped mangabeys.

Yawn contagion (YC) is, compared to spontaneous yawning, an evolutionary recent phenomenon probably linked to behavioral synchronization in highly social species that is more likely when it involves familiar subjects. Here, we investigate for the first time in monkeys which factors modulate intra- and interspecific YC. Through an experimental approach, we exposed 17 red-capped mangabeys to video stimuli (Yawn vs Control) depicting familiar/unfamiliar red-capped mangabeys and humans, and unfamiliar hamadryas. We found that mangabeys yawned more often in response to Yawn than Control videos independently from the species depicted, demonstrating both intra- and interspecific YC in the tested species. Moreover, both mangabey and human familiar yawning stimuli evoked a stronger yawning response in the subjects compared to the unfamiliar counterparts. Neither the amount of time spent looking frontally at the screen (probability of stimulus perception) nor the levels of self-directed behaviors (a proxy of anxiety) accounted for the results. In conclusion, we provide the first evidence that in non-human primate familiarity modulates both intra- and inter-specific YC. Stimuli emitted by familiar faces somehow ease the mechanisms underlying YC, and this modulation can also apply to heterospecific subjects when previous shared experiences provide the prerequisites for the development of social bonds.

Clinicopathologic characteristics of pancreatic islet amyloidosis in the rhesus macaque (Macaca mulatta) and sooty mangabey (Cercocebus atys).

BACKGROUND: Diabetes mellitus type 2 has been linked to pancreatic islet amyloid deposition in humans and nonhuman primates. The authors hypothesized that diabetic primates would have significant differences in pathology than non-diabetic groups. METHODS: This retrospective study used histopathology and immunohistochemistry to characterize and compare pancreatic islet amyloidosis in 58 diabetic and non-diabetic rhesus macaque (RM) and sooty mangabeys (SM). RESULTS: The pancreatic tissues from diabetic RM and SM showed higher histopathology scores for islet amyloid deposit distribution, severity, and calcification deposits compared to their respective non-diabetic cohorts. Further, these tissues from RM and SM with amyloid deposits showed immunoreactivity to insulin, glucagon, islet amyloid polypeptide, serum amyloid P, and glucagon-like peptide 1. CONCLUSIONS: Histopathology results showed that the defined amyloid characteristics are associated with clinical diabetes in both species. The immunohistochemistry results collectively suggest differences in pancreatic hormones and islet amyloid components among both species and diabetic status.

Tissue-specific transcriptional profiling of plasmacytoid dendritic cells reveals a hyperactivated state in chronic SIV infection.

HIV associated immune activation (IA) is associated with increased morbidity in people living with HIV (PLWH) on antiretroviral therapy, and remains a barrier for strategies aimed at reducing the HIV reservoir. The underlying mechanisms of IA have not been definitively elucidated, however, persistent production of Type I IFNs and expression of ISGs is considered to be one of the primary factors. Plasmacytoid DCs (pDCs) are a major producer of Type I IFN during viral infections, and are highly immunomodulatory in acute HIV and SIV infection, however their role in chronic HIV/SIV infection has not been firmly established. Here, we performed a detailed transcriptomic characterization of pDCs in chronic SIV infection in rhesus macaques, and in sooty mangabeys, a natural host non-human primate (NHP) species that undergoes non-pathogenic SIV infection. We also investigated the immunostimulatory capacity of lymph node homing pDCs in chronic SIV infection by contrasting gene expression of pDCs isolated from lymph nodes with those from blood. We observed that pDCs in LNs, but not blood, produced high levels of IFNα transcripts, and upregulated gene expression programs consistent with T cell activation and exhaustion. We apply a novel strategy to catalogue uncharacterized surface molecules on pDCs, and identified the lymphoid exhaustion markers TIGIT and LAIR1 as highly expressed in SIV infection. pDCs from SIV-infected sooty mangabeys lacked the activation profile of ISG signatures observed in infected macaques. These data demonstrate that pDCs are a primary producer of Type I IFN in chronic SIV infection. Further, this study demonstrated that pDCs trafficking to LNs persist in a highly activated state well into chronic infection. Collectively, these data identify pDCs as a highly immunomodulatory cell population in chronic SIV infection, and a putative therapeutic target to reduce immune activation.

APOBEC3F Constitutes a Barrier to Successful Cross-Species Transmission of Simian Immunodeficiency Virus SIVsmm to Humans.

Simian immunodeficiency virus infecting sooty mangabeys (SIVsmm) has been transmitted to humans on at least nine occasions, giving rise to human immunodeficiency virus type 2 (HIV-2) groups A to I. SIVsmm isolates replicate in human T cells and seem capable of overcoming major human restriction factors without adaptation. However, only groups A and B are responsible for the HIV-2 epidemic in sub-Saharan Africa, and it is largely unclear whether adaptive changes were associated with spread in humans. To address this, we examined the sensitivity of infectious molecular clones (IMCs) of five HIV-2 strains and representatives of five different SIVsmm lineages to various APOBEC3 proteins. We confirmed that SIVsmm strains replicate in human T cells, albeit with more variable replication fitness and frequently lower efficiency than HIV-2 IMCs. Efficient viral propagation was generally dependent on intact vif genes, highlighting the need for counteraction of APOBEC3 proteins. On average, SIVsmm was more susceptible to inhibition by human APOBEC3D, -F, -G, and -H than HIV-2. For example, human APOBEC3F reduced infectious virus yield of SIVsmm by ∼80% but achieved only ∼40% reduction in the case of HIV-2. Functional and mutational analyses of human- and monkey-derived alleles revealed that an R128T polymorphism in APOBEC3F contributes to species-specific counteraction by HIV-2 and SIVsmm Vifs. In addition, a T84S substitution in SIVsmm Vif increased its ability to counteract human APOBEC3F. Altogether, our results confirm that SIVsmm Vif proteins show intrinsic activity against human APOBEC3 proteins but also demonstrate that epidemic HIV-2 strains evolved an increased ability to counteract this class of restriction factors during human adaptation. IMPORTANCE Viral zoonoses pose a significant threat to human health, and it is important to understand determining factors. SIVs infecting great apes gave rise to HIV-1. In contrast, SIVs infecting African monkey species have not been detected in humans, with one notable exception. SIVsmm from sooty mangabeys has crossed the species barrier to humans on at least nine independent occasions and seems capable of overcoming many innate defense mechanisms without adaptation. Here, we confirmed that SIVsmm Vif proteins show significant activity against human APOBEC3 proteins. Our analyses also revealed, however, that different lineages of SIVsmm are significantly more susceptible to inhibition by various human APOBEC3 proteins than HIV-2 strains. Mutational analyses suggest that an R128T substitution in APOBEC3F and a T84S change in Vif contribute to species-specific counteraction by HIV-2 and SIVsmm. Altogether, our results support that epidemic HIV-2 strains acquired increased activity against human APOBEC3 proteins to clear this restrictive barrier.

Seed choice differs by sex in sooty mangabeys (Cercocebus atys).

The sooty mangabey (Cercocebus atys) practices year-round durophagy. A large part of the C. atys diet consists of the oily nut of Sacoglottis gabonensis, which is accessed by post-canine crushing of the hard, protective seed coat. During a typical foraging bout, some seeds are discarded after initial crushing attempts using isometric biting, but the reason mangabeys reject some seeds and break into others is unclear. Although C. atys is sexually dimorphic, little is known about whether differences between males and females affect the selectivity of mechanically protected foods. We studied C. atys feeding on S. gabonensis in the Taï National Park,  Côte d'Ivoire, in July and August 2016. Nuts discarded after an initial crushing attempt were collected and their hardness measured using a Shore D durometer. Measurements were taken in the region of the nut where monkeys attempted to crush it. Hardness values of nuts rejected by adult male (n = 79) and adult female (n = 104) C. atys were compared to those of a control assemblage of nuts collected randomly on the forest floor (n = 69). Nuts rejected by either sex do not differ statistically from the random sample; however, they do differ from each other, with females rejecting harder nuts. This suggests that males are more effective at broaching harder seed husks, and discard seeds based on other factors.

Geographically structured genomic diversity of non-human primate-infecting Treponema pallidum subsp. pertenue.

Many non-human primate species in sub-Saharan Africa are infected with Treponema pallidum subsp. pertenue, the bacterium causing yaws in humans. In humans, yaws is often characterized by lesions of the extremities and face, while T. pallidum subsp. pallidum causes venereal syphilis and is typically characterized by primary lesions on the genital, anal or oral mucosae. It remains unclear whether other T. pallidum subspecies found in humans also occur in non-human primates and how the genomic diversity of non-human primate T. pallidum subsp. pertenue lineages is distributed across hosts and space. We observed orofacial and genital lesions in sooty mangabeys (Cercocebus atys) in Taï National Park, Côte d'Ivoire and collected swabs and biopsies from symptomatic animals. We also collected non-human primate bones from 8 species in Taï National Park and 16 species from 11 other sites across sub-Saharan Africa. Samples were screened for T. pallidum DNA using polymerase chain reactions (PCRs) and we used in-solution hybridization capture to sequence T. pallidum genomes. We generated three nearly complete T. pallidum genomes from biopsies and swabs and detected treponemal DNA in bones of six non-human primate species in five countries, allowing us to reconstruct three partial genomes. Phylogenomic analyses revealed that both orofacial and genital lesions in sooty mangabeys from Taï National Park were caused by T. pallidum subsp. pertenue. We showed that T. pallidum subsp. pertenue has infected non-human primates in Taï National Park for at least 28 years and has been present in two non-human primate species that had not been described as T. pallidum subsp. pertenue hosts in this ecosystem, western chimpanzees (Pan troglodytes verus) and western red colobus (Piliocolobus badius), complementing clinical evidence that started accumulating in Taï National Park in 2014. More broadly, simian T. pallidum subsp. pertenue strains did not form monophyletic clades based on host species or the symptoms caused, but rather clustered based on geography. Geographical clustering of T. pallidum subsp. pertenue genomes might be compatible with cross-species transmission of T. pallidum subsp. pertenue within ecosystems or environmental exposure, leading to the acquisition of closely related strains. Finally, we found no evidence for mutations that confer antimicrobial resistance.

Evolution of SIVsm in humanized mice towards HIV-2.

Through the accumulation of adaptive mutations, HIV-2 originated from SIVsm. To identify these evolutionary changes, a humanized mouse model recapitulated the process that likely enabled this cross-species transmission event. Various adaptive mutations arose, as well as increased virulence and CD4+ T-cell decline as the virus was passaged in humanized mice.

Chasing a ghost: notes on the present distribution and conservation of the sooty mangabey (Cercocebus atys) in Guinea-Bissau, West Africa.

The West-African sooty mangabey (Cercocebus atys) is threatened by habitat loss, hunting for meat consumption, and mortality during crop-foraging events. The species' overall demographic trend is unknown. Presence and distribution in Guinea-Bissau, a country neighbored by Senegal and Republic of Guinea, was confirmed in 1946 but the species was declared extinct in 1989 and not observed in subsequent countrywide expeditions. Narratives of its presence across southern Guinea-Bissau are scattered in reports and occurrence in the eastern part was reported in 2017, but the limits of its distribution are currently unknown. Here, we present recent geo-referenced visual and molecular-based records of the sooty mangabey for three protected areas in southern Guinea-Bissau collected as part of a region-wide survey. Individuals were observed in Cufada Lagoons Natural Park (2015) and Dulombi National Park (NP) (2016) and photographed in Boé NP (2007, 2015 and 2020). Thirty-six samples collected in Boé NP (2017) were identified as sooty mangabey using a 402 base pair fragment of the mitochondrial cytochrome b gene. Our work suggests a wider distribution in Guinea-Bissau than previously described, augments knowledge of the populations' current habitat use and threats, and has implications for efforts to conserve the species in West Africa. Considering the sooty mangabey as the reservoir of the simian immunodeficiency virus that led to the human variant, HIV-2, confirmation that the Guinea-Bissau population is not extinct may lead to a better understanding of early viral jump to humans and consequent epidemic spread, specifically of the HIV-2 Subgroup A. We highlight the need for extra conservation measures by Guinea-Bissau authorities.

Delayed disease progression in HIV-2: the importance of TRIM5α and the retroviral capsid.

HIV-2 is thought to have entered the human population in the 1930s through cross-species transmission of SIV from sooty mangabeys in West Africa. Unlike HIV-1, HIV-2 has not led to a global pandemic, and recent data suggest that HIV-2 prevalence is declining in some West African states where it was formerly endemic. Although many early isolates of HIV-2 were derived from patients presenting with AIDS-defining illnesses, it was noted that a much larger proportion of HIV-2-infected subjects behaved as long-term non-progressors (LTNP) than their HIV-1-infected counterparts. Many HIV-2-infected adults are asymptomatic, maintaining an undetectable viral load for over a decade. However, despite lower viral loads, HIV-2 progresses to clinical AIDS without therapeutic intervention in most patients. In addition, successful treatment with anti-retroviral therapy (ART) is more challenging than for HIV-1. HIV-2 is significantly more sensitive to restriction by host restriction factor tripartite motif TRIM5α than HIV-1, and this difference in sensitivity is linked to differences in capsid structure. In this review we discuss the determinants of HIV-2 disease progression and focus on the important interactions between TRIM5α and HIV-2 capsid in long-term viral control.

SIV progenitor evolution toward HIV: A humanized mouse surrogate model for SIVsm adaptation toward HIV-2.

How SIV progenitors evolved into deadly HIV-1 and HIV-2 following initial cross-species transmission still remains a mystery. Here, we used humanized mice as a human surrogate system to evaluate SIVsm evolution into HIV-2. Increased viral virulence to human CD4+ T cells and adaptive genetic changes were observed during serial passages.

Sooty mangabeys scavenge on nuts cracked by chimpanzees and red river hogs-An investigation of inter-specific interactions around tropical nut trees.

Carrion scavenging is a well-studied phenomenon, but virtually nothing is known about scavenging on plant material, especially on remnants of cracked nuts. Just like meat, the insides of hard-shelled nuts are high in energetic value, and both foods are difficult to acquire. In the Taï forest, chimpanzees (Pan troglodytes) and red river hogs (Potamochoerus porcus) crack nuts by using tools or strong jaws, respectively. In this study, previously collected non-invasive camera trap data were used to investigate scavenging by sooty mangabeys (Cercocebus atys), two species of Guinea fowl (Agelestres meleagrides; Guttera verreauxi), and squirrels (Scrunidae spp.) on the nut remnants cracked by chimpanzees and red river hogs. We investigated how scavengers located nut remnants, by analyzing their visiting behavior in relation to known nut-cracking events. Furthermore, since mangabeys are infrequently preyed upon by chimpanzees, we investigated whether they perceive an increase in predation risk when approaching nut remnants. In total, 190 nut-cracking events were observed in four different areas of Taï National Park, Ivory Coast. We could confirm that mangabeys scavenged on the nuts cracked by chimpanzees and hogs and that this enabled them to access food source that would not be accessible otherwise. We furthermore found that mangabeys, but not the other species, were more likely to visit nut-cracking sites after nut-cracking activities than before, and discuss the potential strategies that the monkeys could have used to locate nut remnants. In addition, mangabeys showed elevated levels of vigilance at the chimpanzee nut-cracking sites compared with other foraging sites, suggesting that they perceived elevated danger at these sites. Scavenging on remnants of cracked nuts is a hitherto understudied type of foraging behavior that could be widespread in nature and increases the complexity of community ecology in tropical rainforests.

Mechanical adaptation of trabecular bone morphology in the mammalian mandible.

Alveolar bone, together with the underlying trabecular bone, fulfils an important role in providing structural support against masticatory forces. Diseases such as osteoporosis or periodontitis cause alveolar bone resorption which weakens this structural support and is a major cause of tooth loss. However, the functional relationship between alveolar bone remodelling within the molar region and masticatory forces is not well understood. This study investigated this relationship by comparing mammalian species with different diets and functional loading (Felis catus, Cercocebus atys, Homo sapiens, Sus scrofa, Oryctolagus cuniculus, Ovis aries). We performed histomorphometric analyses of trabecular bone morphology (bone volume fraction, trabecular thickness and trabecular spacing) and quantified the variation of bone and tooth root volumes along the tooth row. A principal component analysis and non-parametric MANOVA showed statistically significant differences in trabecular bone morphology between species with contrasting functional loading, but these differences were not seen in sub-adult specimens. Our results support a strong, but complex link between masticatory function and trabecular bone morphology. Further understanding of a potential functional relationship could aid the diagnosis and treatment of mandibular diseases causing alveolar bone resorption, and guide the design and evaluation of dental implants.

Proteomics and immunohistochemistry identify the expression of α-cardiac myosin heavy chain in the jaw-closing muscles of sooty mangabeys (order Primates).

OBJECTIVE: The jaw-closing muscles of humans and nonprimate mammals express alpha-cardiac fibers but MyHC α-cardiac has not been identified in the jaw adductors of nonhuman primates. We determined whether MyHC α-cardiac is expressed in the superficial masseter and temporalis muscles of the sooty mangabey (Cercocebus atys), an African Old World monkey that specializes on hard seeds. DESIGN: LC-MS/MS based proteomics was used to identify the presence of MyHC Iα. Immunohistochemistry was used to analyze the composition and distribution of fiber types in the superficial masseter and temporalis muscles of eight C. atys. Serial sections were stained against MyHC α-cardiac (MYH6), as well as MyHC-1 (NOQ7.5.4D), MyHC-2 (MY-32), and MyHC-M (2F4). RESULTS: Proteomics analysis identified the presence of Myosin-6 (MyHC α-cardiac) in both heart atrium and superficial masseter. MyHC α-cardiac was expressed in abundance in the superficial masseter and temporalis muscles of all eight individuals and hybrid fibers were common. CONCLUSIONS: The identification of MyHC α-cardiac in the jaw adductors of sooty mangabeys is a novel finding for nonhuman primates. The abundance of MyHC α-cardiac indicates a fatigue-resistant fiber population characterized by intermediate speed of contraction between pure MyHC-1 and MyHC-2 isoforms. We suggest that α-cardiac fibers may be advantageous to sooty mangabeys, whose feeding behavior includes frequent crushing of relatively large, hard seeds during the power stroke of ingestion. Additional studies comparing jaw-adductor fiber phenotype of hard-object feeding primates and other mammals are needed to explore this relationship further.

Loss of CXCR6 coreceptor usage characterizes pathogenic lentiviruses.

Pandemic HIV-1 originated from the cross-species transmission of SIVcpz, which infects chimpanzees, while SIVcpz itself emerged following the cross-species transmission and recombination of monkey SIVs, with env contributed by the SIVgsn/mus/mon lineage that infects greater spot-nosed, mustached and mona monkeys. SIVcpz and HIV-1 are pathogenic in their respective hosts, while the phenotype of their SIVgsn/mus/mon ancestors is unknown. However, two well-studied SIV infected natural hosts, sooty mangabeys (SMs) and African green monkeys (AGMs), typically remain healthy despite high viral loads; these species express low levels of the canonical coreceptor CCR5, and recent work shows that CXCR6 is a major coreceptor for SIV in these hosts. It is not known what coreceptors were used by the precursors of SIVcpz, whether coreceptor use changed during emergence of the SIVcpz/HIV-1 lineage, and what T cell subsets express CXCR6 in natural hosts. Using species-matched coreceptors and CD4, we show here that SIVcpz uses only CCR5 for entry and, like HIV-1, cannot use CXCR6. In contrast, SIVmus efficiently uses both CXCR6 and CCR5. Coreceptor selectivity was determined by Env, with CXCR6 use abrogated by Pro326 in the V3 crown, which is absent in monkey SIVs but highly conserved in SIVcpz/HIV-1. To characterize which cells express CXCR6, we generated a novel antibody that recognizes CXCR6 of multiple primate species. Testing lymphocytes from SM, the best-studied natural host, we found that CXCR6 is restricted to CD4+ effector memory cells, and is expressed by a sub-population distinct from those expressing CCR5. Thus, efficient CXCR6 use, previously identified in SM and AGM infection, also characterizes a member of the SIV lineage that gave rise to SIVcpz/HIV-1. Loss of CXCR6 usage by SIVcpz may have altered its cell tropism, shifting virus from CXCR6-expressing cells that may support replication without disrupting immune function or homeostasis, towards CCR5-expressing cells with pathogenic consequences.

Jaw-Muscle Fiber Architecture and Leverage in the Hard-Object Feeding Sooty Mangabey are not Structured to Facilitate Relatively Large Bite Forces Compared to Other Papionins.

Numerous studies have sought to link craniofacial morphology with behavioral ecology in primates. Extant hard-object feeders have been of particular interest because of their potential to inform our understanding about the diets of early fossil hominins. Sooty mangabeys (Cercocebus atys) are hard-object feeders that frequently generate what have been described as audibly powerful bites at wide jaw gapes to process materially stiff and hard seeds. We address the hypothesis that sooty mangabeys have features of the masticatory apparatus that facilitate this feeding behavior by comparing fiber architecture and leverage of the masseter and temporalis muscles between sooty mangabeys and three papionin primates that do not specialize on hard objects. Contrary to predictions, sooty mangabeys do not have relatively larger muscle physiologic cross-sectional areas or weights compared to other papionins, nor do they consistently display improved leverage. In this regard, sooty mangabeys differ in their morphology from other hard-object feeders such as tufted capuchins. However, males of all four papionin species converge on a shared pattern of relatively longer anterior superficial masseter fibers compared with female conspecifics, suggesting that males are likely prioritizing muscle stretch to improve gape performance as part of a behavioral repertoire that includes agonistic social interactions and intense male-male competition. These findings strengthen support for the hypothesis that gape display behaviors can exert a strong selective influence throughout the musculoskeletal masticatory apparatus. Results also raise questions about the morphological suitability of extant cercopithecines as models for interpreting feeding behavior and diet in fossil hominins with limited jaw gape capacity. Anat Rec, 301:325-342, 2018. © 2018 Wiley Periodicals, Inc.

Mycobacterium leprae genomes from naturally infected nonhuman primates.

Leprosy is caused by the bacterial pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Apart from humans, animals such as nine-banded armadillos in the Americas and red squirrels in the British Isles are naturally infected with M. leprae. Natural leprosy has also been reported in certain nonhuman primates, but it is not known whether these occurrences are due to incidental infections by human M. leprae strains or by M. leprae strains specific to nonhuman primates. In this study, complete M. leprae genomes from three naturally infected nonhuman primates (a chimpanzee from Sierra Leone, a sooty mangabey from West Africa, and a cynomolgus macaque from The Philippines) were sequenced. Phylogenetic analyses showed that the cynomolgus macaque M. leprae strain is most closely related to a human M. leprae strain from New Caledonia, whereas the chimpanzee and sooty mangabey M. leprae strains belong to a human M. leprae lineage commonly found in West Africa. Additionally, samples from ring-tailed lemurs from the Bezà Mahafaly Special Reserve, Madagascar, and chimpanzees from Ngogo, Kibale National Park, Uganda, were screened using quantitative PCR assays, to assess the prevalence of M. leprae in wild nonhuman primates. However, these samples did not show evidence of M. leprae infection. Overall, this study adds genomic data for nonhuman primate M. leprae strains to the existing M. leprae literature and finds that this pathogen can be transmitted from humans to nonhuman primates as well as between nonhuman primate species. While the prevalence of natural leprosy in nonhuman primates is likely low, nevertheless, future studies should continue to explore the prevalence of leprosy-causing pathogens in the wild.

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

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.

Modeling the evolution of SIV sooty mangabey progenitor virus towards HIV-2 using humanized mice.

HIV-2 is thought to have originated from an SIV progenitor native to sooty mangabeys. To model the initial human transmission and understand the sequential viral evolution, humanized mice were infected with SIVsm and serially passaged for five generations. Productive infection was seen by week 3 during the initial challenge followed by chronic viremia and gradual CD4+ T cell decline. Viral loads increased by the 5th generation resulting in more rapid CD4+ T cell decline. Genetic analysis revealed several amino acid substitutions that were nonsynonymous and fixed in multiple hu-mice across each of the 5 generations in the nef, env and rev regions. The highest rate of substitution occurred in the nef and env regions and most were observed within the first two generations. These data demonstrated the utility of hu-mice in modeling the SIVsm transmission to the human and to evaluate its potential sequential evolution into a human pathogen of HIV-2 lineage.