Vaccine-induced neutralizing antibodies bind to the H protein of a historical measles virus.

Measles is a highly contagious airborne viral disease. It can lead to serious complications and death and is preventable by vaccination. The live-attenuated measles vaccine (LAMV) derived from a measles virus (MV) isolated in 1954 has been in use globally for six decades and protects effectively by providing a durable humoral and cell-mediated immunity. Our study addresses the temporal stability of epitopes on the viral surface glycoprotein hemagglutinin (H) which is the major target of MV-neutralizing antibodies. We investigated the binding of seven vaccine-induced MV-H-specific monoclonal antibodies (mAbs) to cell-free synthesized MV-H proteins derived from the H gene sequences obtained from a lung specimen of a fatal case of measles pneumonia in 1912 and an isolate from a current case. The binding of four out of seven mAbs to the H protein of both MV strains provides evidence of epitopes that are stable for more than 100 years. The binding of the universally neutralizing mAbs RKI-MV-12b and RKI-MV-34c to the H protein of the 1912 MV suggests the long-term stability of highly conserved epitopes on the MV surface.

Brain structure and function: a multidisciplinary pipeline to study hominoid brain evolution.

To decipher the evolution of the hominoid brain and its functions, it is essential to conduct comparative studies in primates, including our closest living relatives. However, strong ethical concerns preclude in vivo neuroimaging of great apes. We propose a responsible and multidisciplinary alternative approach that links behavior to brain anatomy in non-human primates from diverse ecological backgrounds. The brains of primates observed in the wild or in captivity are extracted and fixed shortly after natural death, and then studied using advanced MRI neuroimaging and histology to reveal macro- and microstructures. By linking detailed neuroanatomy with observed behavior within and across primate species, our approach provides new perspectives on brain evolution. Combined with endocranial brain imprints extracted from computed tomographic scans of the skulls these data provide a framework for decoding evolutionary changes in hominin fossils. This approach is poised to become a key resource for investigating the evolution and functional differentiation of hominoid brains.

Kiwira Virus, a Newfound Hantavirus Discovered in Free-tailed Bats (Molossidae) in East and Central Africa.

A novel hantavirus, named Kiwira virus, was molecularly detected in six Angolan free-tailed bats (Mops condylurus, family Molossidae) captured in Tanzania and in one free-tailed bat in the Democratic Republic of Congo. Hantavirus RNA was found in different organs, with the highest loads in the spleen. Nucleotide sequences of large parts of the genomic S and L segments were determined by in-solution hybridisation capture and high throughput sequencing. Phylogenetic analyses placed Kiwira virus into the genus Mobatvirus of the family Hantaviridae, with the bat-infecting Quezon virus and Robina virus as closest relatives. The detection of several infected individuals in two African countries, including animals with systemic hantavirus infection, provides evidence of active replication and a stable circulation of Kiwira virus in M. condylurus bats and points to this species as a natural host. Since the M. condylurus home range covers large regions of Sub-Saharan Africa and the species is known to roost inside and around human dwellings, a potential spillover of the Kiwira virus to humans must be considered.

Archival influenza virus genomes from Europe reveal genomic variability during the 1918 pandemic.

The 1918 influenza pandemic was the deadliest respiratory pandemic of the 20th century and determined the genomic make-up of subsequent human influenza A viruses (IAV). Here, we analyze both the first 1918 IAV genomes from Europe and the first from samples prior to the autumn peak. 1918 IAV genomic diversity is consistent with a combination of local transmission and long-distance dispersal events. Comparison of genomes before and during the pandemic peak shows variation at two sites in the nucleoprotein gene associated with resistance to host antiviral response, pointing at a possible adaptation of 1918 IAV to humans. Finally, local molecular clock modeling suggests a pure pandemic descent of seasonal H1N1 IAV as an alternative to the hypothesis of origination through an intrasubtype reassortment.

Tolerance and Persistence of Ebola Virus in Primary Cells from Mops condylurus, a Potential Ebola Virus Reservoir.

Although there have been documented Ebola virus disease outbreaks for more than 40 years, the natural reservoir host has not been identified. Recent studies provide evidence that the Angolan free-tailed bat (Mops condylurus), an insectivorous microbat, is a possible ebolavirus reservoir. To investigate the potential role of this bat species in the ecology of ebolaviruses, replication, tolerance, and persistence of Ebola virus (EBOV) were investigated in 10 different primary bat cell isolates from M. condylurus. Varying EBOV replication kinetics corresponded to the expression levels of the integral membrane protein NPC1. All primary cells were highly tolerant to EBOV infection without cytopathic effects. The observed persistent EBOV infection for 150 days in lung primary cells, without resultant selective pressure leading to virus mutation, indicate the intrinsic ability of EBOV to persist in this bat species. These results provide further evidence for this bat species to be a likely reservoir of ebolaviruses.

Leprosy in wild chimpanzees.

Humans are considered as the main host for Mycobacterium leprae1, the aetiological agent of leprosy, but spillover has occurred to other mammals that are now maintenance hosts, such as nine-banded armadillos and red squirrels2,3. Although naturally acquired leprosy has also been described in captive nonhuman primates4-7, the exact origins of infection remain unclear. Here we describe leprosy-like lesions in two wild populations of western chimpanzees (Pan troglodytes verus) in Cantanhez National Park, Guinea-Bissau and Taï National Park, Côte d'Ivoire, West Africa. Longitudinal monitoring of both populations revealed the progression of disease symptoms compatible with advanced leprosy. Screening of faecal and necropsy samples confirmed the presence of M. leprae as the causative agent at each site and phylogenomic comparisons with other strains from humans and other animals show that the chimpanzee strains belong to different and rare genotypes (4N/O and 2F). These findings suggest that M. leprae may be circulating in more wild animals than suspected, either as a result of exposure to humans or other unknown environmental sources.

Molecular archeology of human viruses.

The evolution of human-virus associations is usually reconstructed from contemporary patterns of genomic diversity. An intriguing, though still rarely implemented, alternative is to search for the genetic material of viruses in archeological and medical archive specimens to document evolution as it happened. In this chapter, we present lessons from ancient DNA research and incorporate insights from virology to explore the potential range of applications and likely limitations of archeovirological approaches. We also highlight the numerous questions archeovirology will hopefully allow us to tackle in the near future, and the main expected roadblocks to these avenues of research.

Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks.

Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak-between 14 February and 19 June 2021-near the epicentre of the previous epidemic1,2. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency. The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization.

A great ape perspective on the origins and evolution of human viruses.

Over the last two decades, the viromes of our closest relatives, the African great apes (AGA), have been intensively studied. Comparative approaches have unveiled diverse evolutionary patterns, highlighting both stable host-virus associations over extended evolutionary timescales and much more recent viral emergence events. In this chapter, we summarize these findings and outline how they have shed a new light on the origins and evolution of many human-infecting viruses. We also show how this knowledge can be used to better understand the evolution of human health in relation to viral infections.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Clinically Relevant ESBL-Producing K. pneumoniae ST307 and E. coli ST38 in an Urban West African Rat Population.

High-risk ESBL-producing Enterobacteriaceae (ESBL-E) have been described in wild birds and rodents worldwide. Rats are of special interest not only due to their indicator role for environmental pollution with multi-resistant bacteria but also as possible infection source. Data on the presence of high-risk ESBL-E in urban wildlife from Africa remain scarce, however. Twenty-nine animals from three different rat (Rattus) species were captured in the city of Conakry (Guinea, West Africa) in 2015. Rectal swabs were analyzed for ESBL-E using selective media. Species typing and phenotypic antimicrobial resistance analysis to broad-spectrum beta-lactams and other classes of antimicrobials was performed for Enterobacteriaceae-like isolates using the VITEK®2 system (BioMérieux, Germany). Confirmed ESBL-producing E. coli and K. pneumoniae were whole-genome sequenced and resistance genes, phylogenetic background and genes related to bacterial fitness and virulence were analyzed. In total, six of twenty-nine rats (20%) carried ESBL-E (K. pneumoniae and E. coli). All ESBL-producers were multi-drug resistant with blaCTX-M-15 as the dominating ESBL-type. Interestingly, ESBL-associated clonal lineages E. coli ST38 and K. pneumoniae ST307 were found. The ESBL-plasmid in K. pneumoniae ST307 revealed high sequence similarities to pKPN3-307_TypeC, a >200 kbp IncFII plasmid originating from a human clinical ST307 isolate. This was in contrast to the core genome: the rat isolate was distantly related to the human clinical ST307 isolate (27 SNPs/Mbp). In addition, we identified π-fimbrial, capsule 2, and glycogen synthesis clusters in the rodent ST307 isolate, whose involvement in the adaptation to survival outside the host and in human urinary tracts has been suggested. Our results demonstrate the presence of clinically relevant, ESBL-producing K. pneumoniae ST307 and E. coli ST38 clonal lineages in an urban West African rat population. The human community is likely the initial source of ESBL-E however, rats might function as infection source and transmission hub, accelerated by frequent interactions at a human-wildlife interface.

Low antibody prevalence against Bacillus cereus biovar anthracis in Taï National Park, Côte d'Ivoire, indicates high rate of lethal infections in wildlife.

Bacillus cereus biovar anthracis (Bcbva) is a member of the B. cereus group which carries both B. anthracis virulence plasmids, causes anthrax-like disease in various wildlife species and was described in several sub-Saharan African rainforests. Long-term monitoring of carcasses in Taï National Park, Côte d'Ivoire, revealed continuous wildlife mortality due to Bcbva in a broad range of mammalian species. While non-lethal anthrax infections in wildlife have been described for B. anthracis, nothing is known about the odds of survival following an anthrax infection caused by Bcbva. To address this gap, we present the results of a serological study of anthrax in five wildlife species known to succumb to Bcbva in this ecosystem. Specific antibodies were only detected in two out of 15 wild red colobus monkeys (Procolobus badius) and one out of 10 black-and-white colobus monkeys (Colobus polykomos), but in none of 16 sooty mangabeys (Cercocebus atys), 9 chimpanzees (Pan troglodytes verus) and 9 Maxwell's duikers (Cephalophus maxwellii). The combination of high mortality and low antibody detection rates indicates high virulence of this disease across these different mammalian species.

Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest.

Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation.