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Identifying genes under local adaptation is an essential step to understand the mechanisms of adaptive evolution. Pathogen-mediated selection is expected to enhance host fitness by favouring resistance to locally prevalent pathogens. However, such pathogen-driven adaptation has been documented in only a few natural systems. Here, we sequenced the Major Histocompatibility Complex Class I region (MHC-I) of 739 Mastomys natalensis captured in Guinea and Nigeria, where the rodent is reservoir to two distinct Lassa virus (LASV) lineages. As predicted, the MHC-I profiles of the two countries, while showing overlap, did not cluster together. Moreover, different MHC-I alleles were associated with active or past infection measured as PCR-positive or IgG-positive, respectively, in each population. MHC-I allele ManaMHC-I*017 showed a diametric response, with individuals carrying this allele less likely to be found with an ongoing LASV infection in Guinea while more likely in Nigeria. Similarly, individuals with ManaMHC-I*069 were less likely to have a positive antibody test in Guinea but the same allele had little effect on IgG detection in Nigeria, suggesting that an individual’s fitness depends on its immunogenetic repertoire. Together, these findings encapsulate a genetically characterised case of local adaptation in a wild virus–rodent system. Moreover, we hypothesise that aside from differences in virus diversity, genetic variation within regional LASV lineages contributes to the marked differences in host immunogenetic diversity.

Lassa fever is a longstanding public health concern in West Africa. Recent molecular studies have confirmed the fundamental role of the rodent host ( Mastomys natalensis ) in driving human infections, but control and prevention efforts remain hampered by a limited baseline understanding of the disease’s true incidence, geographical distribution and underlying drivers. Here, we show that Lassa fever occurrence and incidence is influenced by climate, poverty, agriculture and urbanisation factors. However, heterogeneous reporting processes and diagnostic laboratory access also appear to be important drivers of the patchy distribution of observed disease incidence. Using spatiotemporal predictive models we show that including climatic variability added retrospective predictive value over a baseline model (11% decrease in out-of-sample predictive error). However, predictions for 2020 show that a climate-driven model performs similarly overall to the baseline model. Overall, with ongoing improvements in surveillance there may be potential for forecasting Lassa fever incidence to inform health planning. Lassa Fever is a rodent-borne viral haemorrhagic fever that is a public health problem in West Africa. Here, the authors develop a spatiotemporal model of the socioecological drivers of disease using surveillance data from Nigeria, and find evidence of climate sensitivity.

Lassa fever is a viral haemorrhagic fever caused by an arenavirus. The disease is endemic in West African countries, including Guinea. The rodents Mastomys natalensis and Mastomys erythroleucus have been identified as Lassa virus reservoirs in Guinea. In the absence of a vaccine, rodent control and human behavioural changes are the only options to prevent Lassa fever in highly endemic areas. We performed a 4 year intervention based on chemical rodent control, utilizing anticoagulant rodenticides in 3 villages and evaluating the rodent abundance before and after treatment. Three additional villages were investigated as controls. Analyses to assess the effectiveness of the intervention, bait consumption and rodent dynamics were performed. Anthropological investigations accompanied the intervention to integrate local understandings of human-rodent cohabitation and rodent control intervention. Patterns of bait consumption showed a peak at days 5-7 and no consumption at days 28-30. There was no difference between Bromadiolone and Difenacoum bait consumption. The main rodent species found in the houses was M. natalensis. The abundance of M. natalensis, as measured by the trapping success, varied between 3.6 and 16.7% before treatment and decreased significantly to 1-2% after treatment. Individuals in treated villages welcomed the intervention and trapping because mice are generally regarded as a nuisance. Immediate benefits from controlling rodents included protection of food and belongings. Before the intervention, local awareness of Lassa fever was non-existent. Despite their appreciation for the intervention, local individuals noted its limits and the need for complementary actions. Our results demonstrate that chemical treatment provides an effective tool to control local rodent populations and can serve as part of an effective, holistic approach combining rodent trapping, use of local rodenticides, environmental hygiene, house repairs and rodent-proof storage. These actions should be developed in collaboration with local stakeholders and communities.

The black rat ( Rattus rattus ) is a globally invasive species that has been widely introduced across Africa. Within its invasive range in West Africa, R. rattus may compete with the native rodent Mastomys natalensis , the primary reservoir host of Lassa virus, a zoonotic pathogen that kills thousands annually. Here, we use rodent trapping data from Sierra Leone and Guinea to show that R. rattus presence reduces M. natalensis density within the human dwellings where Lassa virus exposure is most likely to occur. Further, we integrate infection data from M. natalensis to demonstrate that Lassa virus zoonotic spillover risk is lower at sites with R. rattus . While non-native species can have numerous negative effects on ecosystems, our results suggest that R. rattus invasion has the indirect benefit of decreasing zoonotic spillover of an endemic pathogen, with important implications for invasive species control across West Africa. Mastomys natalensis is a rodent species native to West Africa that is the primary reservoir host for Lassa virus. Here, the authors investigate whether the invasive rodent Rattus rattus decreases M. natalensis density and could therefore indirectly decrease zoonotic transmission of Lassa virus to humans.

Lassa virus (LASV) outbreaks in West Africa pose a significant public health threat. We investigated the infection phenotype and transmission (horizontal and vertical) of LASV strain Ba366 in its natural host, Mastomys natalensis . Here we analyze viral RNA levels in body fluids, virus titers in organs and antibody presence in blood. In adults and 2-week-old animals, LASV causes transient infections with subsequent seroconversion. However, mice younger than two weeks exhibit persistent infections lasting up to 16 months despite antibody presence. LASV can be detected in various body fluids, organs, and cell types, primarily in lung, kidney, and gonadal epithelial cells. Despite the systemic virus presence, no pathological alterations in organs are observed. Infected animals efficiently transmit the virus throughout their lives. Our findings underscore the crucial role of persistently infected individuals, particularly infected females and their progeny, in LASV dissemination within the host population. Mastomys natalensis , a mouse found closely to rural human dwellings in Sub-Saharan Africa, is a major reservoir for Lassa Virus (LASV). Here, the authors show that LASV causes transient infections in adult M. natalensis , but persistent infections in young animals despite antibodies. LASV is found in various organs without causing pathology and infected animals efficiently transmit the virus.

Lassa virus (LASV) causes a deadly haemorrhagic fever in humans, killing several thousand people in West Africa annually. For 40 years, the Natal multimammate rat, Mastomys natalensis , has been assumed to be the sole host of LASV. We found evidence that LASV is also hosted by other rodent species: the African wood mouse Hylomyscus pamfi in Nigeria, and the Guinea multimammate mouse Mastomys erythroleucus in both Nigeria and Guinea. Virus strains from these animals were isolated in the BSL-4 laboratory and fully sequenced. Phylogenetic analyses of viral genes coding for glycoprotein, nucleoprotein, polymerase and matrix protein show that Lassa strains detected in M. erythroleucus belong to lineages III and IV. The strain from H. pamfi clusters close to lineage I (for S gene) and between II & III (for L gene). Discovery of new rodent hosts has implications for LASV evolution and its spread into new areas within West Africa.

Orthohantaviruses, negative-sense single-strand tripartite RNA viruses, are a global public health threat. In humans, orthohantavirus infection causes hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Whole-genome sequencing of the virus helps in identification and characterization of emerging or re-emerging viruses. Next-generation sequencing (NGS) is a potent method to sequence the viral genome, using molecular enrichment methods, from clinical specimens containing low virus titers. Hence, a comparative study on the target enrichment NGS methods is required for whole-genome sequencing of orthohantavirus in clinical samples. In this study, we used the sequence-independent, single-primer amplification, target capture, and amplicon NGS for whole-genome sequencing of Hantaan orthohantavirus (HTNV) from rodent specimens. We analyzed the coverage of the HTNV genome based on the viral RNA copy number, which is quantified by real-time quantitative PCR. Target capture and amplicon NGS demonstrated a high coverage rate of HTNV in Apodemus agrarius lung tissues containing up to 10 3 –10 4 copies/μL of HTNV RNA. Furthermore, the amplicon NGS showed a 10-fold (10 2 copies/μL) higher sensitivity than the target capture NGS. This report provides useful insights into target enrichment NGS for whole-genome sequencing of orthohantaviruses without cultivating the viruses.

Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone's centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon's range, but do not, strongly suggesting host-intrinsic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.

Kupffer cells are specialized, liver-resident macrophages that play central roles in hepatic homeostasis, immune surveillance and pathogen clearance. While well-studied in laboratory mice and rats, methods for isolating and studying Kupffer cells from non-model species remain scarce, limiting research in ecologically and zoonotically relevant hosts such as the Natal multimammate mouse ( ), the natural reservoir of Lassa virus (LASV). We developed and validated an optimized Kupffer cell isolation protocol adaptable to non-model rodents, relying on mechanical and enzymatic liver dissociation, non-parenchymal cell enrichment by Percoll gradient and selection by adherence. Critical parameters affecting yield and viability included maintaining all perfusion and digestion steps at 37 °C, limiting enzymatic digestion to ≤15min and avoiding aggressive mechanical disruption. Under optimized conditions, yields averaged 2.55 ± 1.13 × 10 viable Kupffer cells per gram of liver (≈80% viability). Isolated cells displayed macrophage-like morphology, expressed a Kupffer cell marker profile (CD11b /Iba1 /MHC-II /CD80 ) and demonstrated phagocytic and pinocytic activity. As proof-of-concept, Kupffer cells were infected with LASV or Mopeia virus (MOPV). Both successfully infected Kupffer cells, but infection kinetics differed; LASV persisted at stable levels without cytopathic effect, whereas MOPV replication declined over time, suggesting virus-specific control mechanisms. This protocol provides a robust, reproducible, and species-flexible method for isolating viable Kupffer cells from non-model rodents without requiring species-specific reagents. It enables functional, phenotypic, and virological studies in primary hepatic macrophages from and can be adapted to other wildlife reservoirs, supporting comparative immunology, zoonotic disease ecology, and host-pathogen interaction research in under-characterized species.

Over the past decades, the number of arthropod-borne virus (arbovirus) outbreaks has increased worldwide. Knowledge regarding the sylvatic cycle (i.e., non-human hosts/environment) of arboviruses is limited, particularly in Africa, and the main hosts for virus maintenance are unknown. Previous studies have shown the presence of antibodies against certain arboviruses (i.e., chikungunya-, dengue-, and Zika virus) in African non-human primates and bats. We hypothesize that small mammals, specifically rodents, may function as amplifying hosts in anthropogenic environments. The detection of RNA of most arboviruses is complicated by the viruses’ short viremic period within their hosts. An alternative to determine arbovirus hosts is by detecting antibodies, which can persist several months. Therefore, we developed a high-throughput multiplex immunoassay to detect antibodies against 15 medically relevant arboviruses. We used this assay to assess approximately 1,300 blood samples of the multimammate mouse, Mastomys natalensis from Tanzania. In 24% of the samples, we detected antibodies against at least one of the tested arboviruses, with high seroprevalences of antibodies reacting against dengue virus serotype one (7.6%) and two (8.4%), and chikungunya virus (6%). Seroprevalence was higher in females and increased with age, which could be explained by inherent immunity and behavioral differences between sexes, and the increased chance of exposure to an arbovirus with age. We evaluated whether antibodies against multiple arboviruses co-occur more often than randomly and found that this may be true for some members of the Flaviviridae and Togaviridae . In conclusion, the development of an assay against a wide diversity of medically relevant arboviruses enabled the analysis of a large sample collection of one of the most abundant African small mammals. Our findings highlight that Mastomys natalensis is involved in the transmission cycle of multiple arboviruses and provide a solid foundation to better understand the role of this ubiquitous rodent in arbovirus outbreaks.