Sabrina Locatelli

African origin of the malaria parasite Plasmodium vivax

Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa.

Cross-species transmission of simian retroviruses: how and why they could lead to the emergence of new diseases in the human population.

The HIV-1 group M epidemic illustrates the extraordinary impact and consequences resulting from a single zoonotic transmission. Exposure to blood or other secretions of infected animals, through hunting and butchering of bushmeat, or through bites and scratches inflicted by pet nonhuman primates (NHPs), represent the most plausible source for human infection with simian immunodeficiency virus (SIV), simian T-cell lymphotropic virus (STLV) and simian foamy virus. The chance for cross-species transmissions could increase when frequency of exposure and retrovirus prevalence is high. According to the most recent data, human exposure to SIV or STLV appears heterogeneous across the African countries surveyed. Exposure is not sufficient to trigger disease: viral and host molecular characteristics and compatibility are fundamental factors to establish infection. A successful species jump is achieved when the pathogen becomes transmissible between individuals within the new host population. To spread efficiently, HIV likely required changes in human behavior. Given the increasing exposure to NHP pathogens through hunting and butchering, it is likely that SIV and other simian viruses are still transmitted to the human population. The behavioral and socio-economic context of the twenty-first century provides favorable conditions for the emergence and spread of new epidemics. Therefore, it is important to evaluate which retroviruses the human population is exposed to and to better understand how these viruses enter, infect, adapt and spread to its new host.

Molecular epidemiology of simian immunodeficiency virus infection in wild-living gorillas.

ABSTRACT Chimpanzees and gorillas are the only nonhuman primates known to harbor viruses closely related to HIV-1. Phylogenetic analyses showed that gorillas acquired the simian immunodeficiency virus SIVgor from chimpanzees, and viruses from the SIVcpz/SIVgor lineage have been transmitted to humans on at least four occasions, leading to HIV-1 groups M, N, O, and P. To determine the geographic distribution, prevalence, and species association of SIVgor, we conducted a comprehensive molecular epidemiological survey of wild gorillas in Central Africa. Gorilla fecal samples were collected in the range of western lowland gorillas (n = 2,367) and eastern Grauer gorillas (n = 183) and tested for SIVgor antibodies and nucleic acids. SIVgor antibody-positive samples were identified at 2 sites in Cameroon, with no evidence of infection at 19 other sites, including 3 in the range of the Eastern gorillas. In Cameroon, based on DNA and microsatellite analyses of a subset of samples, we estimated the prevalence of SIVgor to be 1.6% (range, 0% to 4.6%), which is significantly lower than the prevalence of SIVcpzPtt in chimpanzees (5.9%; range, 0% to 32%). All newly identified SIVgor strains formed a monophyletic lineage within the SIVcpz radiation, closely related to HIV-1 groups O and P, and clustered according to their field site of origin. At one site, there was evidence for intergroup transmission and a high intragroup prevalence. These isolated hot spots of SIVgor-infected gorilla communities could serve as a source for human infection. The overall low prevalence and sporadic distribution of SIVgor could suggest a decline of SIVgor in wild populations, but it cannot be excluded that SIVgor is still more prevalent in other parts of the geographical range of gorillas.

Evidence from Cameroon reveals differences in the genetic structure and histories of chimpanzee populations

The history of the genus Pan is a topic of enduring interest. Chimpanzees (Pan troglodytes) are often divided into subspecies, but the population structure and genetic history of chimpanzees across Africa remain unclear. Some population genetics studies have led to speculation that, until recently, this species constituted a single population with ongoing gene flow across its range, which resulted in a continuous gradient of allele frequencies. Chimpanzees, designated here as P. t. ellioti, occupy the Gulf of Guinea region that spans southern Nigeria and western Cameroon at the center of the distribution of this species. Remarkably, few studies have included individuals from this region, hindering the examination of chimpanzee population structure across Africa. Here, we analyzed microsatellite genotypes of 94 chimpanzees, including 32 designated as P. t. ellioti. We find that chimpanzees fall into three major populations: (i) Upper Guinea in western Africa (P. t. verus); (ii) the Gulf of Guinea region (P. t. ellioti); and (iii) equatorial Africa (P. t. troglodytes and P. t. schweinfurthii). Importantly, the Gulf of Guinea population is significantly different genetically from the others, sharing a last common ancestor with the populations in Upper Guinea ~0.46 million years ago (mya) and equatorial Africa ~0.32 mya. Equatorial chimpanzees are subdivided into up to three populations occupying southern Cameroon, central Africa, and eastern Africa, which may have constituted a single population until ~0.10–0.11 mya. Finally, occasional hybridization may be occurring between the Gulf of Guinea and southern Cameroon populations.

Evidence for continuing cross-species transmission of SIVsmm to humans: characterization of a new HIV-2 lineage in rural Côte d'Ivoire.

HIV types 1 and 2 (HIV-1 and HIV-2) are the result of multiple cross-species transmissions of their simian counterparts (SIVs) to humans. We studied whether new SIVs lineages have been transmitted to humans in rural Côte d’Ivoire and identified a novel HIV-2 variant (HIV-2-07IC-TNP03) not related to any of the previously defined HIV-2 groups. This finding shows that sooty mangabey viruses continue to be transmitted to humans, causing new zoonotic outbreaks.

No evidence for transmission of SIVwrc from western red colobus monkeys (piliocolobus badius badius) to wild west african chimpanzees (pan troglodytes verus) despite high exposure through hunting

BackgroundSimian Immunodeficiency Viruses (SIVs) are the precursors of Human Immunodeficiency Viruses (HIVs) which have lead to the worldwide HIV/AIDS pandemic. By studying SIVs in wild primates we can better understand the circulation of these viruses in their natural hosts and habitat, and perhaps identify factors that influence susceptibility and transmission within and between various host species. We investigated the SIV status of wild West African chimpanzees (Pan troglodytes verus) which frequently hunt and consume the western red colobus monkey (Piliocolobus badius badius), a species known to be infected to a high percentage with its specific SIV strain (SIVwrc).ResultsBlood and plasma samples from 32 wild chimpanzees were tested with INNO-LIA HIV I/II Score kit to detect cross-reactive antibodies to HIV antigens. Twenty-three of the samples were also tested for antibodies to 43 specific SIV and HIV lineages, including SIVwrc. Tissue samples from all but two chimpanzees were tested for SIV by PCRs using generic SIV primers that detect all known primate lentiviruses as well as primers designed to specifically detect SIVwrc. Seventeen of the chimpanzees showed varying degrees of cross-reactivity to the HIV specific antigens in the INNO-LIA test; however no sample had antibodies to SIV or HIV strain - and lineage specific antigens in the Luminex test. No SIV DNA was found in any of the samples.ConclusionsWe could not detect any conclusive trace of SIV infection from the red colobus monkeys in the chimpanzees, despite high exposure to this virus through frequent hunting. The results of our study raise interesting questions regarding the host-parasite relationship of SIVwrc and wild chimpanzees in their natural habitat.

Chimpanzee population structure in Cameroon and Nigeria is associated with habitat variation that may be lost under climate change

BackgroundThe Nigeria-Cameroon chimpanzee (Pan troglodytes ellioti) is found in the Gulf of Guinea biodiversity hotspot located in western equatorial Africa. This subspecies is threatened by habitat fragmentation due to logging and agricultural development, hunting for the bushmeat trade, and possibly climate change. Although P. t. ellioti appears to be geographically separated from the neighboring central chimpanzee (P. t. troglodytes) by the Sanaga River, recent population genetics studies of chimpanzees from across this region suggest that additional factors may also be important in their separation. The main aims of this study were: 1) to model the distribution of suitable habitat for P. t. ellioti across Cameroon and Nigeria, and P. t. troglodytes in southern Cameroon, 2) to determine which environmental factors best predict their optimal habitats, and 3) to compare modeled niches and test for their levels of divergence from one another. A final aim of this study was to examine the ways that climate change might impact suitable chimpanzee habitat across the region under various scenarios.ResultsEcological niche models (ENMs) were created using the software package Maxent for the three populations of chimpanzees that have been inferred to exist in Cameroon and eastern Nigeria: (i) P. t. troglodytes in southern Cameroon, (ii) P. t. ellioti in northwestern Cameroon, and (iii) P. t. ellioti in central Cameroon. ENMs for each population were compared using the niche comparison test in ENMtools, which revealed complete niche divergence with very little geographic overlap of suitable habitat between populations.ConclusionsThese findings suggest that a positive relationship may exist between environmental variation and the partitioning of genetic variation found in chimpanzees across this region. ENMs for each population were also projected under three different climate change scenarios for years 2020, 2050, and 2080. Suitable habitat of P. t. ellioti in northwest Cameroon / eastern Nigeria is expected to remain largely unchanged through 2080 in all considered scenarios. In contrast, P. t. ellioti in central Cameroon, which represents half of the population of this subspecies, is expected to experience drastic reductions in its ecotone habitat over the coming century.

The population genetics of wild chimpanzees in Cameroon and Nigeria suggests a positive role for selection in the evolution of chimpanzee subspecies

BackgroundChimpanzees (Pan troglodytes) can be divided into four subspecies. Substantial phylogenetic evidence suggests that these subspecies can be grouped into two distinct lineages: a western African group that includes P. t. verus and P. t. ellioti and a central/eastern African group that includes P. t. troglodytes and P. t. schweinfurthii. The geographic division of these two lineages occurs in Cameroon, where the rages of P. t. ellioti and P. t. troglodytes appear to converge at the Sanaga River. Remarkably, few population genetic studies have included wild chimpanzees from this region.ResultsWe analyzed microsatellite genotypes of 187 wild, unrelated chimpanzees, and mitochondrial control region sequencing data from 604 chimpanzees. We found that chimpanzees in Cameroon and eastern Nigeria comprise at least two, and likely three populations. Both the mtDNA and microsatellite data suggest that there is a primary separation of P. t. troglodytes in southern Cameroon from P. t. ellioti north and west of the Sanaga River. These two populations split ~200-250 thousand years ago (kya), but have exchanged one migrant per generation since separating. In addition, P. t. ellioti consists of two populations that split from one another ~4 kya. One population is located in the rainforests of western Cameroon and eastern Nigeria, whereas the second population appears to be confined to a savannah-woodland mosaic in central Cameroon.ConclusionsOur findings suggest that there are as many as three genetically distinct populations of chimpanzees in Cameroon and eastern Nigeria. P. t. troglodytes in southern Cameroon comprises one population that is separated from two populations of P. t. ellioti in western and central Cameroon, respectively. P. t. ellioti and P. t. troglodytes appear to be characterized by a pattern of isolation-with-migration, and thus, we propose that neutral processes alone can not explain the differentiation of P. t. ellioti and P. t. troglodytes.

Origin of the human malaria parasite Plasmodium falciparum in gorillas

Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.

The Evolution of Resistance to Simian Immunodeficiency Virus (SIV): A Review

Examining how pathogens cross species boundaries, spread within species, and persist within their hosts is an essential part of understanding the factors that underpin the evolution of virulence and host resistance. Here, we review current knowledge about the genetic diversity, molecular epidemiology, prevalence, and pathogenicity of simian immunodeficiency viruses (SIVs). SIVs have crossed species boundaries from simian hosts to humans on at least 12 separate occasions, one of which led to the global HIV–AIDS crisis. Though SIVs infect a wide range of primates, scientists have only recently begun to describe the natural history of SIV infection in their natural hosts. Several new studies reveal how both viral and host factors are responsible for the transmission to, and adaptation in, new hosts. These studies also suggest that the spread of the virus may be affected by host-specific traits, including social structure, mating system and demographic history. These studies challenge the traditional view that SIV is relatively benign in its natural host, and instead suggest that a highly dynamic relationship exists between SIV and its simian hosts.