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Forecasting the risk of pathogen spillover from reservoir populations of wild or domestic animals is essential for the effective deployment of interventions such as wildlife vaccination or culling. Due to the sporadic nature of spillover events and limited availability of data, developing and validating robust, spatially explicit, predictions is challenging. Recent efforts have begun to make progress in this direction by capitalizing on machine learning methodologies. An important weakness of existing approaches, however, is that they generally rely on combining human and reservoir infection data during the training process and thus conflate risk attributable to the prevalence of the pathogen in the reservoir population with the risk attributed to the realized rate of spillover into the human population. Because effective planning of interventions requires that these components of risk be disentangled, we developed a multi-layer machine learning framework that separates these processes. Our approach begins by training models to predict the geographic range of the primary reservoir and the subset of this range in which the pathogen occurs. The spillover risk predicted by the product of these reservoir specific models is then fit to data on realized patterns of historical spillover into the human population. The result is a geographically specific spillover risk forecast that can be easily decomposed and used to guide effective intervention. Applying our method to Lassa virus, a zoonotic pathogen that regularly spills over into the human population across West Africa, results in a model that explains a modest but statistically significant portion of geographic variation in historical patterns of spillover. When combined with a mechanistic mathematical model of infection dynamics, our spillover risk model predicts that 897,700 humans are infected by Lassa virus each year across West Africa, with Nigeria accounting for more than half of these human infections.

Marburg and Ebola viruses can cause large hemorrhagic fever (HF) outbreaks with high case fatality (80-90%) in human and great apes. Identification of the natural reservoir of these viruses is one of the most important topics in this field and a fundamental key to understanding their natural history. Despite the discovery of this virus family almost 40 years ago, the search for the natural reservoir of these lethal pathogens remains an enigma despite numerous ecological studies. Here, we report the discovery of Marburg virus in a common species of fruit bat (Rousettus aegyptiacus) in Gabon as shown by finding virus-specific RNA and IgG antibody in individual bats. These Marburg virus positive bats represent the first naturally infected non-primate animals identified. Furthermore, this is the first report of Marburg virus being present in this area of Africa, thus extending the known range of the virus. These data imply that more areas are at risk for MHF outbreaks than previously realized and correspond well with a recently published report in which three species of fruit bats were demonstrated to be likely reservoirs for Ebola virus.

Here we describe the complete genome of a new ebolavirus, Bombali virus (BOMV) detected in free-tailed bats in Sierra Leone (little free-tailed ( Chaerephon pumilus ) and Angolan free-tailed ( Mops condylurus )). The bats were found roosting inside houses, indicating the potential for human transmission. We show that the viral glycoprotein can mediate entry into human cells. However, further studies are required to investigate whether exposure has actually occurred or if BOMV is pathogenic in humans. Genomic characterization of a new ebolavirus, detected in free-tailed bats in Sierra Leone, whose viral glycoprotein can mediate entry into human cells.

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.

Bats are increasingly studied for their ability to coexist with diverse viruses of human health importance. While this focus has yielded insights into host–pathogen dynamics, baseline physiological data from healthy bats remain limited, constraining comparative and mechanistic understanding. Serum proteomics offers a direct window into circulating proteins that underpin immune regulation, cellular maintenance, and metabolism. Here, we characterize the serum proteome of clinically healthy, captive Egyptian rousette bats ( Rousettus aegyptiacus ), the only known natural reservoir host species of Marburg virus. Using untargeted proteomic profiling, we identified and ranked over 400 proteins across major functional categories. Prominent findings included extensive representation of complement components spanning all activation pathways, high levels of interferon-responsive proteins, and abundant proteasome subunits, including immunoproteasome components. The dataset further revealed a robust profile of oxidoreductases and antioxidant enzymes, consistent with mechanisms of redox balance and iron regulation, alongside an apolipoprotein profile suggestive of dietary specialization. An unexpected finding was the unusually high abundance of type XX collagen, potentially linked to tissue remodeling demands of flight. Exploratory sex-based analyses suggested trends in stress response and immune-related proteins, although sample size limited statistical resolution. This work provides the first-look of the Egyptian rousette bat serum proteome, providing a reference point for cross-species comparisons and future studies of bat immunity, metabolism, and longevity. By identifying constitutive molecular features in healthy individuals, these findings expand the use of proteomics for understanding non-traditional model organisms and set the stage for future targeted functional investigations.

Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that has caused large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Currently, no licensed vaccine or therapeutics exists to treat this potentially deadly disease. The explosive nature of RVFV outbreaks and the severe consequences of its accidental or intentional introduction into RVFV-free areas provide the impetus for the development of novel vaccine candidates for use in both livestock and humans. Rationally designed vaccine candidates using reverse genetics have been used to develop deletion mutants of two known RVFV virulence factors, the NSs and NSm genes. These recombinant viruses were demonstrated to be protective and immunogenic in rats, mice, and sheep, without producing clinical illness in these animals. Here, we expand upon those findings and evaluate the single deletion mutant (ΔNSs rRVFV) and double deletion mutant (ΔNSs-ΔNSm rRVFV) vaccine candidates in the common marmoset (Callithrix jacchus), a non-human primate (NHP) model resembling severe human RVF disease. We demonstrate that both the ΔNSs and ΔNSs-ΔNSm rRVFV vaccine candidates were found to be safe and immunogenic in the current study. The vaccinated animals received a single dose of vaccine that led to the development of a robust antibody response. No vaccine-induced adverse reactions, signs of clinical illness or infectious virus were detected in the vaccinated marmosets. All vaccinated animals that were subsequently challenged with RVFV were protected against viremia and liver disease. In summary, our results provide the basis for further development of the ΔNSs and ΔNSs-ΔNSm rRVFV as safe and effective human RVFV vaccines for this significant public health threat.

Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening.

Egyptian rousette bats (Rousettus aegyptiacus) are natural reservoir hosts of Marburg virus (MARV), and Ravn virus (RAVV; collectively called marburgviruses) and have been linked to human cases of Marburg virus disease (MVD). We investigated the clinical and pathologic effects of experimental MARV infection in Egyptian rousettes through a serial euthanasia study and found clear evidence of mild but transient disease. Three groups of nine, captive-born, juvenile male bats were inoculated subcutaneously with 10,000 TCID50 of Marburg virus strain Uganda 371Bat2007, a minimally passaged virus originally isolated from a wild Egyptian rousette. Control bats (n = 3) were mock-inoculated. Three animals per day were euthanized at 3, 5–10, 12 and 28 days post-inoculation (DPI); controls were euthanized at 28 DPI. Blood chemistry analyses showed a mild, statistically significant elevation in alanine aminotransferase (ALT) at 3, 6 and 7 DPI. Lymphocyte and monocyte counts were mildly elevated in inoculated bats after 9 DPI. Liver histology revealed small foci of inflammatory infiltrate in infected bats, similar to lesions previously described in wild, naturally-infected bats. Liver lesion severity scores peaked at 7 DPI, and were correlated with both ALT and hepatic viral RNA levels. Immunohistochemical staining detected infrequent viral antigen in liver (3–8 DPI, n = 8), spleen (3–7 DPI, n = 8), skin (inoculation site; 3–12 DPI, n = 20), lymph nodes (3–10 DPI, n = 6), and oral submucosa (8–9 DPI, n = 2). Viral antigen was present in histiocytes, hepatocytes and mesenchymal cells, and in the liver, antigen staining co-localized with inflammatory foci. These results show the first clear evidence of very mild disease caused by a filovirus in a reservoir bat host and provide support for our experimental model of this virus-reservoir host system.

In humans, Rift Valley fever virus (RVFV) infection typically presents as a self-limiting febrile illness but can cause severe complications. Neurological disease manifestations are particularly concerning as they are associated with increased mortality and long-term morbidity. This study demonstrated that vaccination with live attenuated RVFV was effective in preventing central nervous system (CNS) disease in the CC057/Unc mouse model of late-onset RVF encephalitis. Vaccine candidates (ΔNSs and ΔNSsΔNSm) were safe and immunogenic and elicited both RVFV-specific humoral and cellular immunity. Vaccinated mice survived percutaneous wild-type (WT) RVFV challenge and were protected from CNS disease. Naïve mice that received passive transfer of serum from vaccinated animals 2 days post-WT challenge were protected against late-onset encephalitis. These data demonstrate that humoral immunity is sufficient to protect against RVF encephalitis in CC057/Unc mice and suggest the potential of these vaccine candidates to prevent CNS disease in humans.

Climate change is expected to significantly alter the ecological dynamics of zoonotic diseases, yet its long-term impact on rodent-borne hemorrhagic fevers in South America remains poorly understood. Here, we developed a robust predictive modeling framework that integrates species distribution models with a mechanistic force-of-infection approach to evaluate the effects of climate change on zoonotic risk of New World Arenaviruses. Using climate projections under Shared Socioeconomic Pathways SSP2-4.5 (moderate) and SSP5-8.5 (severe), our models predict a substantial increase in spillover risk across endemic and non-endemic regions over the next two decades. Projected increases in spillover risk for Guanarito, Machupo, and Junin viruses are primarily driven by climate-induced shifts in temperature seasonality, reduced precipitation, and expanding anthropogenic land use, particularly cropland and urban areas within reservoir habitats. Our projections identify transboundary arenaviral hotspots, underscoring the urgent need for coordinated climate-adaptive public health policies, including cross-border surveillance efforts, land-use planning, and resilient rural health systems.