Therapeutic activity and biodistribution of a nano-sized polymer-dexamethasone conjugate intended for the targeted treatment of rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory autoimmune disease caused by alteration of the immune system. Current therapies have several limitations and the use of nanomedicines represents a promising strategy to overcome them. By employing a mouse model of adjuvant induced arthritis, we aimed to evaluate the biodistribution and therapeutic effects of glucocorticoid dexamethasone conjugated to a nanocarrier based on biocompatible N-(2-hydroxypropyl) methacrylamide copolymers. We observed an increased accumulation of dexamethasone polymer nanomedicines in the arthritic mouse paw using non-invasive fluorescent in vivo imaging and confirmed it by the analysis of tissue homogenates. The dexamethasone conjugate exhibited a dose-dependent healing effect on arthritis and an improved therapeutic outcome compared to free dexamethasone. Particularly, significant reduction of accumulation of RA mediator RANKL was observed. Overall, our data suggest that the conjugation of dexamethasone to a polymer nanocarrier by means of stimuli-sensitive spacer is suitable strategy for improving rheumatoid arthritis therapy.

Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases.

The application of polymer-based drug delivery systems is advantageous for improved pharmacokinetics, controlled drug release, and decreased side effects of therapeutics for inflammatory disease. Herein, we describe the synthesis and characterization of linear N-(2-hydroxypropyl)methacrylamide-based polymer conjugates designed for controlled release of the anti-inflammatory drug dexamethasone through pH-sensitive bonds. The tailored release rates were achieved by modifying DEX with four oxo-acids introducing reactive oxo groups to the DEX derivatives. Refinement of reaction conditions yielded four well-defined polymer conjugates with varied release profiles which were more pronounced at the lower pH in cell lysosomes. In vitro evaluations in murine peritoneal macrophages, human synovial fibroblasts, and human peripheral blood mononuclear cells demonstrated that neither drug derivatization nor polymer conjugation affected cytotoxicity or anti-inflammatory properties. Subsequent in vivo tests using a murine arthritis model validated the superior anti-inflammatory efficacy of the prepared DEX-bearing conjugates with lower release rates. These nanomedicines showed much higher therapeutic activity compared to the faster release systems or DEX itself.

The bii4africa dataset of faunal and floral population intactness estimates across Africa's major land uses.

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species' population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate 'intactness scores': the remaining proportion of an 'intact' reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region's major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems.

Trypanosome diversity in small mammals in Uganda and the spread of Trypanosoma lewisi to native species.

Uganda's diverse small mammalian fauna thrives due to its rich habitat diversity, which hosts a wide range of blood parasites, including trypanosomes, particularly the subgenus Herpetosoma typical for rodent hosts. We screened a total of 711 small mammals from various habitats for trypanosomes, with 253 microscopically examined blood smears and 458 tissue samples tested by nested PCR of the 18S rRNA gene. Of 51 rodent and 12 shrew species tested, microscopic screening reaches 7% overall prevalence (with four rodent species positive out of 15 and none of the shrew species out of four), while nested PCR indicated a prevalence of 13% (17 rodent and five shrew species positive out of 49 and 10, respectively). We identified 27 genotypes representing 11 trypanosome species, of which the majority (24 genotypes/9 species) belong to the Herpetosoma subgenus. Among these, we detected 15 new genotypes and two putative new species, labeled AF24 (found in Lophuromys woosnami) and AF25 (in Graphiurus murinus). Our finding of three new genotypes of the previously detected species AF01 belonging to the subgenus Ornithotrypanum in two Grammomys species and Oenomys hypoxanthus clearly indicates the consistent occurrence of this avian trypanosome in African small mammals. Additionally, in Aethomys hindei, we detected the putative new species of the subgenus Aneza. Within the T. lewisi subclade, we detected eleven genotypes, including six new; however, only the genotype AF05b from Mus and Rattus represents the invasive T. lewisi. Our study has improved our understanding of trypanosome diversity in African small mammals. The detection of T. lewisi in native small mammals expands the range of host species and highlighting the need for a broader approach to the epidemiology of T. lewisi.

Lack of host specialization despite selective host use in brood parasitic cuckoo catfish.

Host-parasite dynamics involve coevolutionary arms races, which may lead to host specialization and ensuing diversification. Our general understanding of the evolution of host specialization in brood parasites is compromised by a restricted focus on bird and insect lineages. The cuckoo catfish (Synodontis multipunctatus) is an obligate parasite of parental care of mouthbrooding cichlids in Lake Tanganyika. Given the ecological and taxonomic diversity of mouthbrooding cichlids in the lake, we hypothesized the existence of sympatric host-specific lineages in the cuckoo catfish. In a sample of 779 broods from 20 cichlid species, we found four species parasitized by cuckoo catfish (with prevalence of parasitism of 2%-18%). All parasitized cichlids were from the tribe Tropheini, maternal mouthbrooders that spawn over a substrate (rather than in open water). Phylogenetic analysis based on genomic (ddRAD sequencing) and mitochondrial (Dloop) data from cuckoo catfish embryos showed an absence of host-specific lineages. This was corroborated by analyses of genetic structure and co-ancestry matrix. Within host species, parasitism was not associated with any individual characteristic we recorded (parent size, water depth), but was costly as parasitized parents carried smaller clutches of their own offspring. We conclude that the cuckoo catfish is an intermediate generalist and discuss costs, benefits and constraints of host specialization in this species and brood parasites in general.

Subspecific rodent taxa as the relevant host taxonomic level for mammarenavirus host specificity.

Mastomys natalensis-borne mammarenaviruses appear specific to subspecific M. natalensis taxa rather than to the whole species. Yet mammarenaviruses carried by M. natalensis are known to spill over and jump hosts in northern sub-Saharan Africa. Phylogeographic studies increasingly show that, like M. natalensis, small mammals in sub-Saharan Africa are often genetically structured into several subspecific taxa. Other mammarenaviruses may thus also form virus-subspecific host taxon associations. To investigate this, and if mammarenaviruses carried by M. natalensis in southern Africa are less prone to spill-over, we screened 1225 non-M. natalensis samples from Tanzania where many small mammal taxa meet. We found mammarenavirus RNA in 6 samples. Genetic/genomic characterisation confirmed they were not spill-over from M. natalensis. We detected host jumps among rodent tribe members and an association between mammarenaviruses and subspecific taxa of Mus minutoides and Grammomys surdaster, indicating host genetic structure may be crucial to understand virus distribution and host specificity.

Cryptic diversity of Crocidura shrews in the savannahs of Eastern and Southern Africa.

Crocidura (Eulipotyphla, Soricidae) is the most species-rich genus among mammals, with high cryptic diversity and complicated taxonomy. The hirta-flavescens group of Crocidura represents the most abundant and widespread shrews in savannahs of eastern and southern Africa, making them a suitable phylogeographical model for assessing the role of paleoclimatic changes on current biodiversity in open African habitats. We present the first comprehensive study on the phylogeography, evolutionary history, geographical distribution, systematics, and taxonomy of the group, using the integration of mitochondrial, genome-wide (ddRAD sequencing), morphological and morphometrical data collected from specimens over most of the known geographic distribution. Our genomic data confirmed the monophyly of this group and its sister relationship with the olivieri group of Crocidura. There is a substantial genetic variation within the hirta-flavescens group, with three highly supported clades showing parapatric distribution and which can be distinguished morphologically: C. hirta, distributed in both the Zambezian and Somali-Masai bioregions, C. flavescens, known from South Africa and south-western Zambia, and C. cf. flavescens, which is known to occur only in central and western Tanzania. Morphometric data revealed relatively minor differences between C. hirta and C. cf. flavescens, but they differ in the colouration of the pelage. Diversification of the hirta-flavescens group has most likely happened during phases of grassland expansion and contraction during Plio-Pleistocene climatic cycles. Eastern African Rift system, rivers, and the distinctiveness of Zambezian and Somali-Masai bioregions seem to have also shaped the pattern of their diversity, which is very similar to sympatric rodent species living in open habitats. Finally, we review the group's taxonomy and propose to revalidate C. bloyeti, currently a synonym of C. hirta, including the specimens treated as C. cf. flavescens.

Unexpectedly high diversity of trypanosomes in small sub-Saharan mammals.

The extremely species-rich genus Trypanosoma has recently been divided into 16 subgenera, most of which show fairly high host specificity, including the subgenus Herpetosoma parasitizing mainly rodents. Although most Herpetosoma spp. are highly host-specific, the best-known representative, Trypanosoma lewisi, has a cosmopolitan distribution and low host specificity. The present study investigates the general diversity of small mammal trypanosomes in East and Central Africa and the penetration of invasive T. lewisi into communities of native rodents. An extensive study of blood and tissue samples from Afrotropical micromammals (1528 rodents, 135 shrews, and five sengis belonging to 37 genera and 133 species) captured in the Central African Republic, Ethiopia, Kenya, Malawi, Mozambique, Tanzania, and Zambia revealed 187 (11.2%) trypanosome-positive individuals. The prevalence of trypanosomes in host genera ranged from 2.1% in Aethomys to 37.1% in Lemniscomys. The only previously known trypanosome detected in our dataset was T. lewisi, newly found in Ethiopia, Kenya, and Tanzania in a wide range of native rodent hosts. Besides T. lewisi, 18S rRNA sequencing revealed 48 additional unique Herpetosoma genotypes representing at least 15 putative new species, which doubles the known sequence-based diversity of this subgenus, and approaches the true species richness in the study area. The other two genotypes represent two new species belonging to the subgenera Ornithotrypanum and Squamatrypanum. The trypanosomes of white-toothed shrews (Crocidura spp.) form a new phylogroup of Herpetosoma, unrelated to flagellates previously detected in insectivores. With 13 documented species, Ethiopia was the richest region for trypanosome diversity, which corresponds to the very diverse environments and generally high biodiversity of this country. We conclude that besides T. lewisi, the subgenus Herpetosoma is highly host-specific (e.g., species parasitizing the rodent genera Acomys and Gerbilliscus). Furthermore, several newly detected trypanosome species are specific to their endemic hosts, such as brush-furred mice (Lophuromys), dormice (Graphiurus), and white-toothed shrews (Crocidura).

Detection and genetic diversity of Mopeia virus in Mastomys natalensis from different habitats in the Limpopo National Park, Mozambique.

Mammarenaviruses have been a growing concern for public health in Africa since the 1970s when Lassa virus cases in humans were first described in west Africa. In southern Africa, a single outbreak of Lujo virus was reported to date in South Africa in 2008 with a case fatality rate of 80%. The natural reservoir of Lassa virus is Mastomys natalensis while for the Lujo virus the natural host has yet to be identified. Mopeia virus was described for the first time in M. natalensis in the central Mozambique in 1977 but few studies have been conducted in the region. In this study, rodents were trapped between March and November 2019in villages, croplands fields and mopane woodland forest. The aim was to assess the potential circulation and to evaluate the genetic diversity of mammarenaviruses in M. natalensis trapped in the Limpopo National Park and its buffer zone in Massingir district, Mozambique. A total of 534 M. natalensis were screened by RT-PCR and the overall proportion of positive individuals was 16.9%. No significant differences were detected between the sampled habitats (χ2 = 0.018; DF = 1; p = 0.893). The Mopeia virus (bootstrap value 91%) was the Mammarenavirus circulating in the study area sites, forming a specific sub-clade with eight different sub-clusters. We concluded that Mopeia virus circulates in all habitats investigated and it forms a different sub-clade to the one reported in central Mozambique in 1977.

Molecular detection and genomic characterization of diverse hepaciviruses in African rodents.

Hepatitis C virus (HCV; genus Hepacivirus) represents a major public health problem, infecting about three per cent of the human population. Because no animal reservoir carrying closely related hepaciviruses has been identified, the zoonotic origins of HCV still remain unresolved. Motivated by recent findings of divergent hepaciviruses in rodents and a plausible African origin of HCV genotypes, we have screened a large collection of small mammals samples from seven sub-Saharan African countries. Out of 4,303 samples screened, eighty were found positive for the presence of hepaciviruses in twenty-nine different host species. We, here, report fifty-six novel genomes that considerably increase the diversity of three divergent rodent hepacivirus lineages. Furthermore, we provide strong evidence for hepacivirus co-infections in rodents, which were exclusively found in four sampled species of brush-furred mice. We also detect evidence of recombination within specific host lineages. Our study expands the available hepacivirus genomic data and contributes insights into the relatively deep evolutionary history of these pathogens in rodents. Overall, our results emphasize the importance of rodents as a potential hepacivirus reservoir and as models for investigating HCV infection dynamics.

Phylogenomics of African radiation of Praomyini (Muridae: Murinae) rodents: First fully resolved phylogeny, evolutionary history and delimitation of extant genera.

The tribe Praomyini is a diversified group including 64 species and eight extant rodent genera. They live in a broad spectrum of habitats across whole sub-Saharan Africa. Members of this tribe are often very abundant, they have a key ecological role in ecosystems, they are hosts of many potentially pathogenic microorganisms and comprise numerous agricultural pests. Although this tribe is well supported by both molecular and morphological data, its intergeneric relationships and the species contents of several genera are not yet fully resolved. Recent molecular data suggest that at least three genera in current sense are paraphyletic. However, in these studies the species sampling was sparse and the resolution of relationships among genera was poor, probably due to a fast radiation of the tribe dated to the Miocene and insufficient amount of genetic data. Here we used genomic scale data (395 nuclear loci = 610,965 bp long alignment and mitogenomes = 14,745 bp) and produced the first fully resolved species tree containing most major lineages of the Praomyini tribe (i.e. all but one currently delimited genera and major intrageneric clades). Results of a fossil-based divergence dating analysis suggest that the radiation started during the Messinian stage (ca. 7 Ma) and was likely linked to a fragmentation of the pan-African Miocene forest. Some lineages remained in the rain forests, while many others adapted to a broad spectrum of new open lowland and montane habitats that appeared at the beginning of Pliocene. Our analyses clearly confirmed the presence of three polyphyletic genera (Praomys, Myomyscus and Mastomys). We review current knowledge of these three genera and suggest corresponding taxonomic changes. To keep genera monophyletic, we propose taxonomic re-arrangements and delimit four new genera. Furthermore, we discovered a new highly divergent genetic lineage of Praomyini in southwestern Ethiopia, which is described as a new species and genus.

Prevalence of Orthohantavirus-Reactive Antibodies in Humans and Peri-Domestic Rodents in Northern Ethiopia.

In 2012, Tigray orthohantavirus was discovered in Ethiopia, but its seasonal infection in small mammals, and whether it poses a risk to humans was unknown. The occurrence of small mammals, rodents and shrews, in human inhabitations in northern Ethiopia is affected by season and presence of stone bunds. We sampled small mammals in two seasons from low- and high-density stone bund fields adjacent to houses and community-protected semi-natural habitats in Atsbi and Hagere Selam, where Tigray orthohantavirus was first discovered. We collected blood samples from both small mammals and residents using filter paper. The presence of orthohantavirus-reactive antibodies in blood was then analyzed using immunofluorescence assay (human samples) and enzyme linked immunosorbent assays (small mammal samples) with Puumala orthohantavirus as antigen. Viral RNA was detected by RT-PCR using small mammal blood samples. Total orthohantavirus prevalence (antibodies or virus RNA) in the small mammals was 3.37%. The positive animals were three Stenocephalemys albipes rats (prevalence in this species = 13.04%). The low prevalence made it impossible to determine whether season and stone bunds were associated with orthohantavirus prevalence in the small mammals. In humans, we report the first detection of orthohantavirus-reactive IgG antibodies in Ethiopia (seroprevalence = 5.26%). S. albipes lives in close proximity to humans, likely increasing the risk of zoonotic transmission.

Historical biogeography, systematics, and integrative taxonomy of the non-Ethiopian speckled pelage brush-furred rats (Lophuromys flavopunctatus group).

BACKGROUND: The speckled-pelage brush-furred rats (Lophuromys flavopunctatus group) have been difficult to define given conflicting genetic, morphological, and distributional records that combine to obscure meaningful accounts of its taxonomic diversity and evolution. In this study, we inferred the systematics, phylogeography, and evolutionary history of the L. flavopunctatus group using maximum likelihood and Bayesian phylogenetic inference, divergence times, historical biogeographic reconstruction, and morphometric discriminant tests. We compiled comprehensive datasets of three loci (two mitochondrial [mtDNA] and one nuclear) and two morphometric datasets (linear and geometric) from across the known range of the genus Lophuromys. RESULTS: The mtDNA phylogeny supported the division of the genus Lophuromys into three primary groups with nearly equidistant pairwise differentiation: one group corresponding to the subgenus Kivumys (Kivumys group) and two groups corresponding to the subgenus Lophuromys (L. sikapusi group and L. flavopunctatus group). The L. flavopunctatus group comprised the speckled-pelage brush-furred Lophuromys endemic to Ethiopia (Ethiopian L. flavopunctatus members [ETHFLAVO]) and the non-Ethiopian ones (non-Ethiopian L. flavopunctatus members [NONETHFLAVO]) in deeply nested relationships. There were distinctly geographically structured mtDNA clades among the NONETHFLAVO, which were incongruous with the nuclear tree where several clades were unresolved. The morphometric datasets did not systematically assign samples to meaningful taxonomic units or agree with the mtDNA clades. The divergence dating and ancestral range reconstructions showed the NONETHFLAVO colonized the current ranges over two independent dispersal events out of Ethiopia in the early Pleistocene. CONCLUSION: The phylogenetic associations and divergence times of the L. flavopunctatus group support the hypothesis that paleoclimatic impacts and ecosystem refugia during the Pleistocene impacted the evolutionary radiation of these rodents. The overlap in craniodental variation between distinct mtDNA clades among the NONETHFLAVO suggests unraveling underlying ecomorphological drivers is key to reconciling taxonomically informative morphological characters. The genus Lophuromys requires a taxonomic reassessment based on extensive genomic evidence to elucidate the patterns and impacts of genetic isolation at clade contact zones.

Complex reticulate evolution of speckled brush-furred rats (Lophuromys) in the Ethiopian centre of endemism.

The Ethiopian highlands represent a remarkable biodiversity 'hot spot' with a very high number of endemic species, even among vertebrates. Ethiopian representatives of a species complex of speckled brush-furred rats (Lophuromys flavopunctatus sensu lato) inhabit highland habitats ranging from low-elevation forests to Afroalpine grasslands. These may serve as a suitable model for understanding evolutionary processes leading to high genetic and ecological diversity in montane biodiversity hot spots. Here, we analyse the most comprehensive genetic data set of this group, comprising 315 specimens (all nine putative Ethiopian Lophuromys taxa sampled across most of their distribution ranges) genotyped at one mitochondrial and four nuclear markers, and thousands of SNPs from ddRAD sequencing. We performed phylogenetic analyses, delimited species and mapped their distribution and estimated divergence time between species (under the species-tree framework) and mitochondrial lineages. We found significant incongruence between mitochondrial and nuclear phylogenies, most probably caused by multiple interspecific introgression events. We discuss alternative scenarios of Ethiopian Lophuromys evolution, from retention of ancestral polymorphism to hybridization upon secondary contact of partially reproductively isolated lineages leading to reticulate evolution. Finally, we use the diversity of the speckled brush-furred rats for the description of the main biogeographic patterns in the fauna of the Ethiopian highlands.

Nuclear phylogenomics, but not mitogenomics, resolves the most successful Late Miocene radiation of African mammals (Rodentia: Muridae: Arvicanthini).

The tribe Arvicanthini (Muridae: Murinae) is a highly diversified group of rodents (ca. 100 species) and with 18 African genera (plus one Asiatic) represents probably the most successful adaptive radiation of extant mammals in Africa. They colonized a broad spectrum of habitats (from rainforests to semi-deserts) in whole sub-Saharan Africa and their members often belong to most abundant parts of mammal communities. Despite intensive efforts, the phylogenetic relationships among major lineages (i.e. genera) remained obscured, which was likely caused by the intensive radiation of the group, dated to the Late Miocene. Here we used genomic scale data (377 nuclear loci; 581,030 bp) and produced the first fully resolved species tree containing all currently delimited genera of the tribe. Mitogenomes were also extracted, and while the results were largely congruent, there was less resolution at basal nodes of the mitochondrial phylogeny. Results of a fossil-based divergence dating analysis suggest that the African radiation started early after the colonization of Africa by a single arvicanthine ancestor from Asia during the Messinian stage (ca. 7 Ma), and was likely linked with a fragmentation of the pan-African Miocene forest. Some lineages remained in the rain forest, while many others successfully colonized broad spectrum of new open habitats (e.g. savannas, wetlands or montane moorlands) that appeared at the beginning of Pliocene. One lineage even evolved partially arboricolous life style in savanna woodlands, which allowed them to re-colonize equatorial forests. We also discuss delimitation of genera in Arvicanthini and propose corresponding taxonomic changes.

Mitogenomics of the endemic Ethiopian rats: looking for footprints of adaptive evolution in sky islands.

Organisms living in high altitude must adapt to environmental conditions with hypoxia and low temperature, e.g. by changes in the structure and function of proteins associated with oxidative phosphorylation in mitochondria. Here we analysed the signs of adaptive evolution in 27 mitogenomes of endemic Ethiopian rats (Stenocephalemys), where individual species adapted to different elevation. Significant signals of positive selection were detected in 10 of the 13 mitochondrial protein-coding genes, with a majority of functional substitutions in the NADH dehydrogenase complex. Higher frequency of positively selected sites was found in phylogenetic lineages corresponding to Afroalpine specialists.

Multilocus phylogeny of African striped grass mice (Lemniscomys): Stripe pattern only partly reflects evolutionary relationships.

Murine rodents are one of the most evolutionary successful groups of extant mammals. They are also important for human as vectors and reservoirs of zoonoses and agricultural pests. Unfortunately, their fast and relatively recent diversification impedes our understanding of phylogenetic relationships and species limits of many murine taxa, including those with very conspicuous phenotype that has been frequently used for taxonomic purposes. One of such groups are the striped grass mice (genus Lemniscomys), distributed across sub-Saharan Africa in 11 currently recognized species. These are traditionally classified into three morphological groups according to different pelage colouration on the back: (a) L. barbarus group (three species) with several continuous pale longitudinal stripes; (b) L. striatus group (four species) with pale stripes diffused into short lines or dots; and (c) L. griselda group (four species) with a single mid-dorsal black stripe. Here we reconstructed the most comprehensive molecular phylogeny of the genus Lemniscomys to date, using the largest currently available multi-locus genetic dataset of all but two species. The results show four main lineages (=species complexes) with the distribution corresponding to the major biogeographical regions of Africa. Surprisingly, the four phylogenetic lineages are only in partial agreement with the morphological classification, suggesting that the single-stripe and/or multi-striped phenotypes evolved independently in multiple lineages. Divergence dating showed the split of Lemniscomys and Arvicanthis genera at the beginning of Pleistocene; most of subsequent speciation processes within Lemniscomys were affected by Pleistocene climate oscillations, with predominantly allopatric diversification in fragmented savanna biome. We propose taxonomic suggestions and directions for future research of this striking group of African rodents.

Three arenaviruses in three subspecific natal multimammate mouse taxa in Tanzania: same host specificity, but different spatial genetic structure?

Mastomys natalensis is widespread in sub-Saharan Africa and hosts several arenavirus species, including the pathogenic zoonotic Lassa virus in West Africa. Mitochondrial lineages sub-divide the range of M. natalensis and have been associated with cryptic structure within the species. To test specificity of arenaviruses to hosts carrying these lineages, we screened 1772 M. natalensis in a large area of Tanzania where three mitochondrial lineages meet. We detected fifty-two individuals that were positive for one of three arenaviruses: Gairo, Morogoro, and Luna virus. This is the first record of Luna virus in Tanzania. We confirmed the specificity of each arenavirus to a distinct host mitochondrial lineage except for three cases in one locality at the centre of a host hybrid zone. No arenaviruses were detected in a large part of the study area. Morogoro and Gairo virus showed differences in prevalence (Morogoro virus lower than Gairo virus) and in genetic structure (Morogoro virus more structured than Gairo virus). However, both viruses have genetic neighbourhood size estimates of the same order of magnitude as Lassa virus. While differences in arenavirus and/or host evolutionary and ecological dynamics may exist, Tanzanian arenaviruses could be suited to model Lassa virus dynamics in M. natalensis.

The phylogeny of the African wood mice (Muridae, Hylomyscus) based on complete mitochondrial genomes and five nuclear genes reveals their evolutionary history and undescribed diversity.

Wood mice of the genus Hylomyscus, are small-sized rodents widely distributed in lowland and montane rainforests in tropical Africa, where they can be locally abundant. Recent morphological and molecular studies have increased the number of recognized species from 8 to 18 during the last 15 years. We used complete mitochondrial genomes and five nuclear genes to infer the number of candidate species within this genus and depict its evolutionary history. In terms of gene sampling and geographical and taxonomic coverage, this is the most comprehensive review of the genus Hylomyscus to date. The six species groups (aeta, alleni, anselli, baeri, denniae and parvus) defined on morphological grounds are monophyletic. Species delimitation analyses highlight undescribed diversity within this genus: perhaps up to 10 taxa need description or elevation from synonymy, pending review of type specimens. Our divergence dating and biogeographical analyses show that diversification of the genus occurred after the end of the Miocene and is closely linked to the history of the African forest. The formation of the Rift Valley combined with the declining global temperatures during the Late Miocene caused the fragmentation of the forests and explains the first split between the denniae group and remaining lineages. Subsequently, periods of increased climatic instability during Plio-Pleistocene probably resulted in elevated diversification in both lowland and montane forest taxa.

Tigray Orthohantavirus Infects Two Related Rodent Species Adapted to Different Elevations in Ethiopia.

Orthohantaviruses are RNA viruses that some members are known to cause severe zoonotic diseases in humans. Orthohantaviruses are hosted by rodents, soricomorphs (shrews and moles), and bats. Only two orthohantaviruses associated with murid rodents are known in Africa, Sangassou orthohantavirus (SANGV) in two species of African wood mice (Hylomyscus), and Tigray orthohantavirus (TIGV) in the Ethiopian white-footed rat (Stenocephalemys albipes). In this article, we report evidence that, like SANGV, two strains of TIGV occur in two genetically related rodent species, S. albipes and S. sp. A, occupying different elevational zones in the same mountain. Investigating the other members of the genus Stenocephalemys for TIGV could reveal the real diversity of TIGV in the genus.