Publications by authors named "Fabian H Leendertz"

134 Publications

Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease.

Gut 2021 Apr 22. Epub 2021 Apr 22.

Department of Medicine I, Institute of Cancer Research, Medical University Vienna, Vienna, Austria.

Objective: Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.

Design: We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.

Results: We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.

Conclusion: HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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http://dx.doi.org/10.1136/gutjnl-2020-323868DOI Listing
April 2021

Primate phageomes are structured by superhost phylogeny and environment.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

Epidemiology of Highly Pathogenic Organisms, Robert Koch Institute, 13353 Berlin, Germany;

Humans harbor diverse communities of microorganisms, the majority of which are bacteria in the gastrointestinal tract. These gut bacterial communities in turn host diverse bacteriophage (hereafter phage) communities that have a major impact on their structure, function, and, ultimately, human health. However, the evolutionary and ecological origins of these human-associated phage communities are poorly understood. To address this question, we examined fecal phageomes of 23 wild nonhuman primate taxa, including multiple representatives of all the major primate radiations. We find relatives of the majority of human-associated phages in wild primates. Primate taxa have distinct phageome compositions that exhibit a clear phylosymbiotic signal, and phage-superhost codivergence is often detected for individual phages. Within species, neighboring social groups harbor compositionally and evolutionarily distinct phageomes, which are structured by superhost social behavior. Captive nonhuman primate phageome composition is intermediate between that of their wild counterparts and humans. Phage phylogenies reveal replacement of wild great ape-associated phages with human-associated ones in captivity and, surprisingly, show no signal for the persistence of wild-associated phages in captivity. Together, our results suggest that potentially labile primate-phage associations have persisted across millions of years of evolution. Across primates, these phylosymbiotic and sometimes codiverging phage communities are shaped by transmission between groupmates through grooming and are dramatically modified when primates are moved into captivity.
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http://dx.doi.org/10.1073/pnas.2013535118DOI Listing
April 2021

Discovery of novel herpes simplexviruses in wild gorillas, bonobos, and chimpanzees supports zoonotic origin of HSV-2.

Mol Biol Evol 2021 Mar 15. Epub 2021 Mar 15.

Viral Evolution, Robert Koch Institute, Berlin, Germany.

Viruses closely related to human pathogens can reveal the origins of human infectious diseases. Human herpes simplexvirus type 1 (HSV-1) and type 2 (HSV-2) are hypothesized to have arisen via host-virus co-divergence and cross-species transmission. We report the discovery of novel herpes simplexviruses during a large-scale screening of fecal samples from wild gorillas, bonobos, and chimpanzees. Phylogenetic analysis indicates that, contrary to expectation, simplexviruses from these African apes are all more closely related to HSV-2 than to HSV-1. Molecular clock-based hypothesis testing suggests the divergence between HSV-1 and the African great ape simplexviruses likely represents a codivergence event between humans and gorillas. The simplexviruses infecting African great apes subsequently experienced multiple cross-species transmission events over the past 3 million years, the most recent of which occurred between humans and bonobos around 1 million years ago. These findings revise our understanding of the origins of human herpes simplexviruses and suggest that HSV-2 is one of the earliest zoonotic pathogens.
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http://dx.doi.org/10.1093/molbev/msab072DOI Listing
March 2021

Risk of human-to-wildlife transmission of SARS-CoV-2.

Mamm Rev 2020 Oct 6. Epub 2020 Oct 6.

Department of Biology University of Antwerp Universiteitsplein 1 Antwerp 2610 Belgium.

It has been a long time since the world has experienced a pandemic with such a rapid devastating impact as the current COVID-19 pandemic. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unusual in that it appears capable of infecting many different mammal species. As a significant proportion of people worldwide are infected with SARS-CoV-2 and may spread the infection unknowingly before symptoms occur or without any symptoms ever occurring, there is a non-negligible risk of humans spreading SARS-CoV-2 to wildlife, in particular to wild non-human mammals. Because of SARS-CoV-2's apparent evolutionary origins in bats and reports of humans transmitting the virus to pets and zoo animals, regulations for the prevention of human-to-animal transmission have so far focused mostly on these animal groups. We summarise recent studies and reports that show that a wide range of distantly related mammals are likely to be susceptible to SARS-CoV-2, and that susceptibility or resistance to the virus is, in general, not predictable, or only predictable to some extent, from phylogenetic proximity to known susceptible or resistant hosts. In the absence of solid evidence on the susceptibility and resistance to SARS-CoV-2 for each of the >6500 mammal species, we argue that sanitary precautions should be taken by humans interacting with any other mammal species in the wild. Preventing human-to-wildlife SARS-CoV-2 transmission is important to protect these animals (some of which are classed as threatened) from disease, but also to avoid establishment of novel SARS-CoV-2 reservoirs in wild mammals. The risk of repeated re-infection of humans from such a wildlife reservoir could severely hamper SARS-CoV-2 control efforts. Activities during which direct or indirect interaction with wild mammals may occur include wildlife research, conservation activities, forestry work, pest control, management of feral populations, ecological consultancy work, management of protected areas and natural environments, wildlife tourism and wildlife rehabilitation in animal shelters. During such activities, we recommend sanitary precautions, such as physical distancing, wearing face masks and gloves, and frequent decontamination, which are very similar to regulations currently imposed to prevent transmission among humans. We further recommend active surveillance of domestic and feral animals that could act as SARS-CoV-2 intermediate hosts between humans and wild mammals.
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http://dx.doi.org/10.1111/mam.12225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675675PMC
October 2020

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

Microb Genom 2020 11;6(11)

Viral Evolution, Robert Koch Institute, Berlin, Germany.

Many non-human primate species in sub-Saharan Africa are infected with subsp. , the bacterium causing yaws in humans. In humans, yaws is often characterized by lesions of the extremities and face, while subsp. causes venereal syphilis and is typically characterized by primary lesions on the genital, anal or oral mucosae. It remains unclear whether other subspecies found in humans also occur in non-human primates and how the genomic diversity of non-human primate subsp. lineages is distributed across hosts and space. We observed orofacial and genital lesions in sooty mangabeys () 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 DNA using polymerase chain reactions (PCRs) and we used in-solution hybridization capture to sequence genomes. We generated three nearly complete 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 subsp. . We showed that subsp. 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 subsp. hosts in this ecosystem, western chimpanzees () and western red colobus (), complementing clinical evidence that started accumulating in Taï National Park in 2014. More broadly, simian subsp. strains did not form monophyletic clades based on host species or the symptoms caused, but rather clustered based on geography. Geographical clustering of subsp. genomes might be compatible with cross-species transmission of subsp. within ecosystems or environmental exposure, leading to the acquisition of closely related strains. Finally, we found no evidence for mutations that confer antimicrobial resistance.
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http://dx.doi.org/10.1099/mgen.0.000463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725339PMC
November 2020

Urinary Cortisol Increases During a Respiratory Outbreak in Wild Chimpanzees.

Front Vet Sci 2020 21;7:485. Epub 2020 Aug 21.

Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.

In mammals, the excretion of cortisol can provide energy toward restoring homeostasis and is a major component of the stress response. However, chronically elevated cortisol levels also have suppressive effects on immune function. As mounting an immune response is energetically costly, sick individuals may conserve energy by exhibiting certain sickness behaviors, such as declining activity levels. Due to the complex interplay between immune function and sickness behaviors, endocrinological correlates have received growing attention in the medical community, but so far, this subject was investigated rarely. Furthermore, given the complexities of studying illnesses and immunity in natural settings, correlates of sickness behaviors have yet to be studied in non-human primates in the wild. We measured urinary cortisol levels using liquid chromatography-mass spectrometry in a group of wild habituated chimpanzees in Taï National Park, Côte d'Ivoire, before, during, and after a respiratory disease outbreak (main causative pathogen: human respiratory syncytial virus A, with coinfections of ). Changes in cortisol levels were then related to urinary neopterin levels, a biomarker of immune system activation. Urinary cortisol levels were found to be more than 10-fold higher during the outbreak in comparison with levels before and after the outbreak period. Increasing cortisol levels were also associated with increasing neopterin levels. Interestingly, rather atypical patterns in a diurnal decline of cortisol levels were found during infection periods, such that levels remained raised throughout the day. In conclusion, cortisol increase was related to cellular immune response. Our results suggest that cortisol is a mediator of infectious disease pathogenicity through its impact on the immune system and that wild chimpanzees may be facing energetic stress when sick. By monitoring immune challenges in wild-living animals, our study demonstrates that immune defenses have costs and that these costs are context-specific.
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http://dx.doi.org/10.3389/fvets.2020.00485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472655PMC
August 2020

Role of Wildlife in Emergence of Ebola Virus in Kaigbono (Likati), Democratic Republic of the Congo, 2017.

Emerg Infect Dis 2020 09;26(9):2205-2209

After the 2017 Ebola virus (EBOV) outbreak in Likati, a district in northern Democratic Republic of the Congo, we sampled small mammals from the location where the primary case-patient presumably acquired the infection. None tested positive for EBOV RNA or antibodies against EBOV, highlighting the ongoing challenge in detecting animal reservoirs for EBOV.
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http://dx.doi.org/10.3201/eid2609.191552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454093PMC
September 2020

Measles virus and rinderpest virus divergence dated to the sixth century BCE.

Science 2020 06;368(6497):1367-1370

Epidemiology of Highly Pathogenic Microorganisms Project Group, Robert Koch Institute, Berlin, Germany.

Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the exact date of emergence for this disease is controversial. We sequenced the genome of a 1912 measles virus and used selection-aware molecular clock modeling to determine the divergence date of measles virus and rinderpest virus. This divergence date represents the earliest possible date for the establishment of measles in human populations. Our analyses show that the measles virus potentially arose as early as the sixth century BCE, possibly coinciding with the rise of large cities.
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http://dx.doi.org/10.1126/science.aba9411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713999PMC
June 2020

Author Correction: Evidence for Human Streptococcus pneumoniae in wild and captive chimpanzees: A potential threat to wild populations.

Sci Rep 2020 May 29;10(1):9062. Epub 2020 May 29.

Epidemiology of highly pathogenic microorganisms, Robert Koch-Institute, 13353, Berlin, Germany.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-66183-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260240PMC
May 2020

Yaws Disease Caused by Treponema pallidum subspecies pertenue in Wild Chimpanzee, Guinea, 2019.

Emerg Infect Dis 2020 06;26(6):1283-1286

Yaws-like lesions are widely reported in wild African great apes, yet the causative agent has not been confirmed in affected animals. We describe yaws-like lesions in a wild chimpanzee in Guinea for which we demonstrate infection with Treponema pallidum subsp. pertenue. Assessing the conservation implications of this pathogen requires further research.
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http://dx.doi.org/10.3201/eid2606.191713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258472PMC
June 2020

Serological evidence for human exposure to Bacillus cereus biovar anthracis in the villages around Taï National Park, Côte d'Ivoire.

PLoS Negl Trop Dis 2020 05 14;14(5):e0008292. Epub 2020 May 14.

Robert Koch Institute, Centre for Biological Threats and Special Pathogens, ZBS 2: Highly Pathogenic Microorganisms, Berlin, Germany.

Bacillus cereus biovar anthracis (Bcbva) is an untypical anthrax-causing pathogen responsible for high wildlife mortality in Taï National Park (TNP), Côte d'Ivoire. However, nothing is known about its effect on the rural population living in the region bordering TNP. Contact to bushmeat is a known risk factor for exposure to a variety of zoonotic pathogens, but no human infections with Bcbva were noted so far. Therefore, we performed a retrospective seroprevalence analysis with sera from 1,386 study volunteers. We used assays which detect antibodies against the protective antigen PA, which is synthesized by both Bcbva and classic B. anthracis, and against the recently described antigen pXO2-60, a 35-kDa protein only produced by Bcbva. We found a high seroprevalence (22.37%) of antibodies against PA, and approximately half of those sera (10.46%) were also positive for the Bcbva-specific antigen pXO2-60. All sera negative for PA were also negative for antibodies against pXO2-60, confirming specificity and suitability of the PA/pXO2-60 combined serological assay. The fact that a large fraction of sera was positive for PA but negative for pXO2-60 can most likely be explained by lower immunogenicity of pXO2-60, but exposure to classic B. anthracis cannot be excluded. As only Bcbva has been detected in the TNP area so far, exposure to Bcbva can be suspected from the presence of antibodies against PA alone. In a questionnaire, most study participants reported contact to bushmeat and livestock carcasses. Unfortunately, risk factor analysis indicated that neither animal contacts, sex, age, nor country of origin were significant predictors of Bcbva seroprevalence. Nevertheless, our study added to an assessment of the distribution of Bcbva and its impact on the human population, and our data can serve to raise awareness of anthrax in the affected regions.
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http://dx.doi.org/10.1371/journal.pntd.0008292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224451PMC
May 2020

Monkeypox virus emergence in wild chimpanzees reveals distinct clinical outcomes and viral diversity.

Nat Microbiol 2020 07 27;5(7):955-965. Epub 2020 Apr 27.

Project Group Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, Berlin, Germany.

Monkeypox is a viral zoonotic disease on the rise across endemic habitats. Despite the growing importance of monkeypox virus, our knowledge on its host spectrum and sylvatic maintenance is limited. Here, we describe the recent repeated emergence of monkeypox virus in a wild, human-habituated western chimpanzee (Pan troglodytes verus, hereafter chimpanzee) population from Taï National Park, Ivory Coast. Through daily monitoring, we show that further to causing its typical exanthematous syndrome, monkeypox can present itself as a severe respiratory disease without a diffuse rash. By analysing 949 non-invasively collected samples, we identify the circulation of at least two distinct monkeypox virus lineages and document the shedding of infectious particles in faeces and flies, suggesting that they could mediate indirect transmission. We also show that the carnivorous component of the Taï chimpanzees' diet, mainly consisting of the sympatric monkeys they regularly hunt, did not change nor shift towards rodent consumption (the presumed reservoir) before the outbreaks, suggesting that the sudden emergence of monkeypox virus in this population is probably due to changes in the ecology of the virus itself. Using long-term mortality surveillance data from Taï National Park, we provide evidence of little to no prior viral activity over at least two decades. We conclude that great ape sentinel systems devoted to the longitudinal collection of behavioural and health data can help clarify the epidemiology and clinical presentation of zoonotic pathogens.
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http://dx.doi.org/10.1038/s41564-020-0706-0DOI Listing
July 2020

Differences in MHC-B diversity and KIR epitopes in two populations of wild chimpanzees.

Immunogenetics 2019 11 3;71(10):617-633. Epub 2019 Dec 3.

Department of Primatology, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103, Leipzig, Germany.

The major histocompatibility complex (MHC) class I genes play a critical role within the immune system, both by the presentation of antigens from intracellular pathogens to immunocompetent cells and by the interaction with killer cell immunoglobulin-like receptors (KIR) on natural killer cells (NK cells). Genes of the MHC are highly diverse, and MHC variation can have effects on the immune functionality of individuals; hence, comparisons of MHC diversity among closely related phylogenetic taxa may give insight into the factors responsible for the shaping of its diversity. The four geographically separated chimpanzee subspecies differ in their overall genetic diversity, have different population histories, and are confronted with different pathogens in their natural habitat, all of which may affect MHC class I DNA sequence diversity. Here, we compare the MHC-B exon two DNA sequence diversity from 24 wild western and 46 wild eastern chimpanzees using necropsy and noninvasively collected fecal samples, respectively. We found a higher MHC-B exon two nucleotide diversity, in our western than eastern chimpanzees. The inclusion of previously published MHC-B exon two data from other western and eastern chimpanzees supported this finding. In addition, our results confirm and extend the finding of a very low C1 epitope frequency at eastern chimpanzee MHC-B molecules, which likely affects the ability of these molecules to interact with NK cells. While the understanding of the differing pathogen environments encountered by disparate populations of a species is a challenging endeavor, these findings highlight the potential for these pathogens to selectively shape immune system variation.
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http://dx.doi.org/10.1007/s00251-019-01148-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900261PMC
November 2019

Novel Polyomaviruses in Mammals from Multiple Orders and Reassessment of Polyomavirus Evolution and Taxonomy.

Viruses 2019 10 10;11(10). Epub 2019 Oct 10.

P3 "Viral Evolution", Robert Koch Institute, 13353 Berlin, Germany.

As the phylogenetic organization of mammalian polyomaviruses is complex and currently incompletely resolved, we aimed at a deeper insight into their evolution by identifying polyomaviruses in host orders and families that have either rarely or not been studied. Sixteen unknown and two known polyomaviruses were identified in animals that belong to 5 orders, 16 genera, and 16 species. From 11 novel polyomaviruses, full genomes could be determined. Splice sites were predicted for large and small T antigen (LTAg, STAg) coding sequences (CDS) and examined experimentally in transfected cell culture. In addition, splice sites of seven published polyomaviruses were analyzed. Based on these data, LTAg and STAg annotations were corrected for 10/86 and 74/86 published polyomaviruses, respectively. For 25 polyomaviruses, a spliced middle T CDS was observed or predicted. Splice sites that likely indicate expression of additional, alternative T antigens, were experimentally detected for six polyomaviruses. In contrast to all other mammalian polyomaviruses, three closely related cetartiodactyl polyomaviruses display two introns within their LTAg CDS. In addition, the VP2 of Glis glis (edible dormouse) polyomavirus 1 was observed to be encoded by a spliced transcript, a unique experimental finding within the family. Co-phylogenetic analyses based on LTAg CDS revealed a measurable signal of codivergence when considering all mammalian polyomaviruses, most likely driven by relatively recent codivergence events. Lineage duplication was the only other process whose influence on polyomavirus evolution was unambiguous. Finally, our analyses suggest that an update of the taxonomy of the family is required, including the creation of novel genera of mammalian and non-mammalian polyomaviruses.
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http://dx.doi.org/10.3390/v11100930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833039PMC
October 2019

Detection of possible spillover of a novel hantavirus in a Natal mastomys from Guinea.

Virus Genes 2020 Feb 25;56(1):95-98. Epub 2019 Oct 25.

Robert Koch Institut, Berlin, Germany.

To date, only two rodent-borne hantaviruses have been detected in sub-Saharan Africa. Here, we report the detection of a yet unknown hantavirus in a Natal mastomys (Mastomys natalensis) in Méliandou, Guinea, in 2014. The phylogenetic placement of this virus suggests that it might represent a cross-order spillover event from an unknown bat or eulipotyphlan host.
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http://dx.doi.org/10.1007/s11262-019-01709-4DOI Listing
February 2020

Metabarcoding of eukaryotic parasite communities describes diverse parasite assemblages spanning the primate phylogeny.

Mol Ecol Resour 2020 Jan 4;20(1):204-215. Epub 2019 Nov 4.

Primate Genetics Laboratory, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany.

Despite their ubiquity, in most cases little is known about the impact of eukaryotic parasites on their mammalian hosts. Comparative approaches provide a powerful method to investigate the impact of parasites on host ecology and evolution, though two issues are critical for such efforts: controlling for variation in methods of identifying parasites and incorporating heterogeneity in sampling effort across host species. To address these issues, there is a need for standardized methods to catalogue eukaryotic parasite diversity across broad phylogenetic host ranges. We demonstrate the feasibility of a metabarcoding approach for describing parasite communities by analysing faecal samples from 11 nonhuman primate species representing divergent lineages of the primate phylogeny and the full range of sampling effort (i.e. from no parasites reported in the literature to the best-studied primates). We detected a number of parasite families and regardless of prior sampling effort, metabarcoding of only ten faecal samples identified parasite families previously undescribed in each host (x̅ = 8.5 new families per species). We found more overlap between parasite families detected with metabarcoding and published literature when more research effort-measured as the number of publications-had been conducted on the host species' parasites. More closely related primates and those from the same continent had more similar parasite communities, highlighting the biological relevance of sampling even a small number of hosts. Collectively, results demonstrate that metabarcoding methods are sensitive and powerful enough to standardize studies of eukaryotic parasite communities across host species, providing essential new tools for macroecological studies of parasitism.
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http://dx.doi.org/10.1111/1755-0998.13101DOI Listing
January 2020

Cytomegalovirus distribution and evolution in hominines.

Virus Evol 2019 Jul 1;5(2):vez015. Epub 2019 Aug 1.

Max Planck Institute for Evolutionary Anthropology (MPI EVA), Leipzig, Germany.

Herpesviruses are thought to have evolved in very close association with their hosts. This is notably the case for cytomegaloviruses (CMVs; genus ) infecting primates, which exhibit a strong signal of co-divergence with their hosts. Some herpesviruses are however known to have crossed species barriers. Based on a limited sampling of CMV diversity in the hominine (African great ape and human) lineage, we hypothesized that chimpanzees and gorillas might have mutually exchanged CMVs in the past. Here, we performed a comprehensive molecular screening of all 9 African great ape species/subspecies, using 675 fecal samples collected from wild animals. We identified CMVs in eight species/subspecies, notably generating the first CMV sequences from bonobos. We used this extended dataset to test competing hypotheses with various degrees of co-divergence/number of host switches while simultaneously estimating the dates of these events in a Bayesian framework. The model best supported by the data involved the transmission of a gorilla CMV to the panine (chimpanzee and bonobo) lineage and the transmission of a panine CMV to the gorilla lineage prior to the divergence of chimpanzees and bonobos, more than 800,000 years ago. Panine CMVs then co-diverged with their hosts. These results add to a growing body of evidence suggesting that viruses with a double-stranded DNA genome (including other herpesviruses, adenoviruses, and papillomaviruses) often jumped between hominine lineages over the last few million years.
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http://dx.doi.org/10.1093/ve/vez015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671425PMC
July 2019

Tropical rainforest flies carrying pathogens form stable associations with social nonhuman primates.

Mol Ecol 2019 09 18;28(18):4242-4258. Epub 2019 Jul 18.

Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, Berlin, Germany.

Living in groups provides benefits but also incurs costs such as attracting disease vectors. For example, synanthropic flies associate with human settlements, and higher fly densities increase pathogen transmission. We investigated whether such associations also exist in highly mobile nonhuman primate (NHP) Groups. We studied flies in a group of wild sooty mangabeys (Cercocebus atys atys) and three communities of wild chimpanzees (Pan troglodytes verus) in Taï National Park, Côte d'Ivoire. We observed markedly higher fly densities within both mangabey and chimpanzee groups. Using a mark-recapture experiment, we showed that flies stayed with the sooty mangabey group for up to 12 days and for up to 1.3 km. We also tested mangabey-associated flies for pathogens infecting mangabeys in this ecosystem, Bacillus cereus biovar anthracis (Bcbva), causing sylvatic anthrax, and Treponema pallidum pertenue, causing yaws. Flies contained treponemal (6/103) and Bcbva (7/103) DNA. We cultured Bcbva from all PCR-positive flies, confirming bacterial viability and suggesting that this bacterium might be transmitted and disseminated by flies. Whole genome sequences of Bcbva isolates revealed a diversity of Bcbva, probably derived from several sources. We conclude that flies actively track mangabeys and carry infectious bacterial pathogens; these associations represent an understudied cost of sociality and potentially expose many social animals to a diversity of pathogens.
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http://dx.doi.org/10.1111/mec.15145DOI Listing
September 2019

A Novel Orthohepadnavirus Identified in a Dead Maxwell's Duiker () in Taï National Park, Côte d'Ivoire.

Viruses 2019 03 19;11(3). Epub 2019 Mar 19.

Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, 13353 Berlin, Germany.

New technologies enable viral discovery in a diversity of hosts, providing insights into viral evolution. We used one such approach, the virome capture sequencing for vertebrate viruses (VirCapSeq-VERT) platform, on 21 samples originating from six dead Maxwell's duikers () from Taï National Park, Côte d'Ivoire. We detected the presence of an orthohepadnavirus in one animal and characterized its 3128 bp genome. The highest viral copy numbers were detected in the spleen, followed by the lung, blood, and liver, with the lowest copy numbers in the kidney and heart; the virus was not detected in the jejunum. Viral copy numbers in the blood were in the range known from humans with active chronic infections leading to liver histolytic damage, suggesting this virus could be pathogenic in duikers, though many orthohepadnaviruses appear to be apathogenic in other hosts, precluding a formal test of this hypothesis. The virus was not detected in 29 other dead duiker samples from the Côte d'Ivoire and Central African Republic, suggesting either a spillover event or a low prevalence in these populations. Phylogenetic analysis placed the virus as a divergent member of the mammalian clade of orthohepadnaviruses, though its relationship to other orthohepadnaviruses remains uncertain. This represents the first orthohepadnavirus described in an artiodactyl. We have tentatively named this new member of the genus (family ), Taï Forest hepadnavirus. Further studies are needed to determine whether it, or some close relatives, are present in a broader range of artiodactyls, including livestock.
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http://dx.doi.org/10.3390/v11030279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466360PMC
March 2019

CD4 receptor diversity in chimpanzees protects against SIV infection.

Proc Natl Acad Sci U S A 2019 02 4;116(8):3229-3238. Epub 2019 Feb 4.

Sanaga-Yong Chimpanzee Rescue Center, In Defense of Animals-Africa, Portland, OR 97204.

Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells. Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions. Testing the replication fitness of SIVcpz strains in CD4 T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts. These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes. The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles. In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition. CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan. CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep. One allele was associated with lower SIVcpz prevalence rates in the wild. These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry. Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.
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http://dx.doi.org/10.1073/pnas.1821197116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386711PMC
February 2019

Extensive Serological Survey of Multiple African Nonhuman Primate Species Reveals Low Prevalence of Immunoglobulin G Antibodies to 4 Ebola Virus Species.

J Infect Dis 2019 10;220(10):1599-1608

Recherches Translationelles sur VIH et Maladies Infectieuses/Institut national de la santé et de la recherche médicale, Institut de Recherche pour le Développement and University of Montpellier, France.

Bats are considered a reservoir species for Ebola viruses, but nonhuman primates (NHPs) have represented a source of infection in several outbreaks in humans. Here we report serological screening of blood or fecal samples from monkeys (n = 2322) and apes (n = 2327). Thirty-six NHP species from Cameroon, Democratic Republic of the Congo, and Ivory Coast were tested with a sensitive and specific Luminex-based assay for immunoglobulin G antibodies to 4 Ebola virus species. Using the simultaneous presence of antibodies to nucleoproteins and glycoproteins to define positivity, we showed that specific Ebola virus antibodies are not widespread among NHPs. Only 1 mustached monkey (Cercopithecus cephus) from Cameroon was positive for Sudan ebolavirus. These observations support that NHPs are most likely intermediate hosts for Ebola viruses. With the increasing frequency of Ebola outbreaks, it is crucial to identify the animal reservoir and understand the ecology of Ebola viruses to inform disease control.
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http://dx.doi.org/10.1093/infdis/jiz006DOI Listing
October 2019

Urinary neopterin levels increase and predict survival during a respiratory outbreak in wild chimpanzees (Taï National Park, Côte d'Ivoire).

Sci Rep 2018 09 6;8(1):13346. Epub 2018 Sep 6.

Department of Primatology, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103, Leipzig, Germany.

Monitoring immune system activation of wild animals has garnered increasing interest within the field of ecological immunology, leading to an urgent need for non-invasive biomarkers measuring these changes. Urinary neopterin, a marker of the cell-mediated immune response, is validated as an immune-related biomarker in captive and laboratory animals. However, wild animals naturally host higher and chronic pathogen loads. Therefore, detection and quantification of additional infections via neopterin might not be possible against the background of a chronically challenged immune system. To assess the suitability of urinary neopterin in wild animals, we measured neopterin corrected for specific gravity with an enzyme immunoassay in 185 samples collected before, during and after a respiratory disease outbreak in 28 individuals from a group of wild chimpanzees (Taï National Park, Côte d'Ivoire). Urinary neopterin levels were significantly higher during periods when individuals showed respiratory symptoms versus before and after the outbreak. Furthermore, urinary neopterin levels were significantly higher in individuals that died, with higher levels already apparent before the outbreak, suggesting individuals may have an already activated immune system. Measuring urinary neopterin levels, with other biomarkers of energetic condition, stress challenges, and reproduction will contribute towards a deeper understanding of life-history trade-offs in wild animals.
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http://dx.doi.org/10.1038/s41598-018-31563-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127264PMC
September 2018

Evolutionary history of human revealed by genome-wide analyses of related ape parasites.

Proc Natl Acad Sci U S A 2018 09 20;115(36):E8450-E8459. Epub 2018 Aug 20.

Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104;

Wild-living African apes are endemically infected with parasites that are closely related to human , a leading cause of malaria outside Africa. This finding suggests that the origin of was in Africa, even though the parasite is now rare in humans there. To elucidate the emergence of human and its relationship to the ape parasites, we analyzed genome sequence data of strains infecting six chimpanzees and one gorilla from Cameroon, Gabon, and Côte d'Ivoire. We found that ape and human parasites share nearly identical core genomes, differing by only 2% of coding sequences. However, compared with the ape parasites, human strains of exhibit about 10-fold less diversity and have a relative excess of nonsynonymous nucleotide polymorphisms, with site-frequency spectra suggesting they are subject to greatly relaxed purifying selection. These data suggest that human has undergone an extreme bottleneck, followed by rapid population expansion. Investigating potential host-specificity determinants, we found that ape parasites encode intact orthologs of three reticulocyte-binding protein genes (, , and ), which are pseudogenes in all human strains. However, binding studies of recombinant RBP2e and RBP3 proteins to human, chimpanzee, and gorilla erythrocytes revealed no evidence of host-specific barriers to red blood cell invasion. These data suggest that, from an ancient stock of parasites capable of infecting both humans and apes, a severely bottlenecked lineage emerged out of Africa and underwent rapid population growth as it spread globally.
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http://dx.doi.org/10.1073/pnas.1810053115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130405PMC
September 2018

The Use of Neopterin as a Noninvasive Marker in Monitoring Diseases in Wild Chimpanzees.

Ecohealth 2018 12 16;15(4):792-803. Epub 2018 Aug 16.

Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany.

Pathogen analysis in wild great apes is both time- and resource-consuming. Therefore, we examined the potential use of urinary neopterin, a sensitive marker of cell-mediated immune system activation, as a disease marker and unspecific screening tool to facilitate informed pathogen analysis in great ape health monitoring. To test this, urinary neopterin was correlated to other disease markers such as sickness behaviors, fever, and urine parameters. Seasonal variation in urinary neopterin levels was investigated as well. The study encompassed noninvasively collected longitudinal data of young wild chimpanzees from the Taï National Park, Côte d´Ivoire. Relationships between disease markers were examined using a linear mixed model and a case study approach. Seasonal variation in urinary neopterin was tested using a linear mixed model. While the linear mixed model found no obvious relationship between urinary neopterin levels and other disease markers, the case study approach revealed a pattern resembling those found in humans. Urinary neopterin levels indicated seasonal immune system activation peaking in times of low ambient temperatures. We suggest the use of urinary neopterin as an unspecific screening tool in great ape health monitoring to identify relevant samples, individuals, and time periods for selective pathogen analysis and zoonotic risk assessment.
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http://dx.doi.org/10.1007/s10393-018-1357-yDOI Listing
December 2018

Factors influencing bacterial microbiome composition in a wild non-human primate community in Taï National Park, Côte d'Ivoire.

ISME J 2018 10 28;12(10):2559-2574. Epub 2018 Jun 28.

Project Group Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany.

Microbiomes impact a variety of processes including a host's ability to access nutrients and maintain health. While host species differences in microbiomes have been described across ecosystems, little is known about how microbiomes assemble, particularly in the ecological and social contexts in which they evolved. We examined gut microbiome composition in nine sympatric wild non-human primate (NHP) species. Despite sharing an environment and interspecific interactions, individuals harbored unique and persistent microbiomes influenced by host species, social group, and parentage, but surprisingly not by social relationships among members of a social group. We found a branching order of host-species networks constructed using the composition of their microbiomes as characters, which was incongruent with known NHP phylogenetic relationships, with chimpanzees (Pan troglodytes verus) sister to colobines, upon which they regularly prey. In contrast to phylogenetic clustering found in all monkey microbiomes, chimpanzee microbiomes were unique in that they exhibited patterns of phylogenetic overdispersion. This reflects unique ecological processes impacting microbiome composition in chimpanzees and future studies will elucidate the aspects of chimpanzee ecology, life history, and physiology that explain their unique microbiome community structure. Our study of contemporaneous microbiomes of all sympatric diurnal NHP in an ecosystem highlights the diverse dispersal routes shaping these complex communities.
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http://dx.doi.org/10.1038/s41396-018-0166-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154966PMC
October 2018