Biology subjects

Lemey, P.

Publications and source records attributed to Lemey, P..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Massive outbreak of Influenza A H5N1 in elephant seals at Peninsula Valdes, Argentina: increased evidence for mammal-to-mammal transmission

H5N1 high pathogenicity avian influenza (HPAI) viruses of the clade 2.3.4.4b have killed thousands of marine mammals in South America since 2022. In October 2023, following outbreaks in sea lions in Argentina, we recorded unprecedented mass mortality ([~]17,000 individuals) in southern elephant seals (Mirounga leonina) at Peninsula Valdes. Seal pups were disproportionately affected. Adult seals departed early, disrupting social and breeding structure. Frequent interactions with sea lions and scavenging by seagulls were observed. Deaths of terns concurred with seals but peaked weeks later. HPAI H5N1 was confirmed in seals and terns. Moreover, genomic characterization showed viruses from pinnipeds and terns in Argentina form a distinct clade with marine mammal viruses from Peru, Chile and Brazil. These mammal-clade viruses share an identical set of mammalian adaptation mutations which are notably also found in the terns. Our combined ecological and phylogenetic data support mammal-to-mammal transmission and occasional mammal-to-bird spillover. To our knowledge, this is the first multinational transmission of H5N1 viruses in mammals ever observed globally. The implication that H5N1 viruses are becoming more evolutionary flexible and adapting to mammals in new ways could have global consequences for wildlife, humans, and/or livestock.

microbiology↗

bioRxiv2024

How fast are viruses spreading in the wild?

Genomic data collected from viral outbreaks can be exploited to reconstruct the dispersal history of viral lineages in a two-dimensional space using continuous phylogeographic inference. These spatially explicit reconstructions can subsequently be used to estimate dispersal metrics allowing to unveil the dispersal dynamics and evaluate the capacity to spread among hosts. Heterogeneous sampling intensity of genomic sequences can however impact the accuracy of dispersal insights gained through phylogeographic inference. In our study, we implement a simulation framework to evaluate the robustness of three dispersal metrics -- a lineage dispersal velocity, a diffusion coefficient, and an isolation-by-distance signal metric -- to the sampling effort. Our results reveal that both the diffusion coefficient and isolation-by-distance signal metrics appear to be robust to the number of samples considered for the phylogeographic reconstruction. We then use these two dispersal metrics to compare the dispersal pattern and capacity of various viruses spreading in animal populations. Our comparative analysis reveals a broad range of isolation-by-distance patterns and diffusion coefficients mostly reflecting the dispersal capacity of the main infected host species but also, in some cases, the likely signature of rapid and/or long-distance dispersal events driven by human-mediated movements through animal trade. Overall, our study provides key recommendations for the lineage dispersal metrics to consider in future studies and illustrates their application to compare the spread of viruses in various settings.

evolutionary biology↗

bioRxiv2024

Population genetics, phylogeography and gene flow of mainland and island vampire bat (Desmodus rotundus) populations: an investigation into mainland-island bat movement

Movement of animals and plants from mainland populations contributes to the genetic diversity and viability of geographically isolated island biota, but also carries risks of pathogen introductions. The bat fauna of the island of Trinidad reflects species diversity on the neighbouring South American mainland and includes the common vampire bat (Desmodus rotundus). We determined relationships between Trinidad and mainland vampire bat populations and the extent of mainland-island movement by comparing the genetic structure (nuclear and mitochondrial) and morphology of the Trinidadian D. rotundus population to populations in neighbouring regions of the South American mainland and estimating evolutionary histories and patterns of gene flow. Results indicate that Trinidadian D. rotundus are genetically and morphologically distinct from mainland populations, although limited unidirectional male-biased mainland to island gene flow occurs at an estimated rate of 3.3 migrants per year. Two geographically-defined Desmodus cytochrome b clades were identified within Trinidad (i.e., one restricted to the South-Western peninsula which grouped with Venezuelan sequences and the other found throughout the rest of the island which grouped with sequences from Suriname and Guyana) suggesting long-standing female philopatry. The geographic distribution of these clades mirrors that of two previously identified geographically defined rabies virus (RABV) lineages introduced to Trinidad from the mainland. This finding suggests that bat dispersals and RABV introductions occur via both the northern and south-western island peninsulas, with subsequent male-driven intra-island viral spread enabled by bat nuclear homogeneity of these populations. These study findings will contribute to the development of contemporary evidence-based vampire bat population control and rabies prevention programs within island populations.

evolutionary biology↗

bioRxiv2023

Association of poultry vaccination with the interspecies transmission and molecular evolution of H5 subtype avian influenza virus

The effectiveness of vaccinating poultry in preventing the transmission of highly pathogenic avian influenza viruses (AIVs) has been questioned for years and its impact on wild birds is uncertain 1-3. Here we reconstruct movements of H5 subtype AIV lineages among vaccinated poultry, unvaccinated poultry, and wild birds, worldwide from 1996 to 2023. We find that lineage transitions among host types are lagged and that movements from wild birds to unvaccinated poultry were more frequent than those from wild birds to vaccinated poultry. However, we also find that the HA gene of the AIV lineage that circulated predominately among Chinese poultry with high vaccination coverage underwent faster evolution and greater nonsynonymous divergence than other lineages. Further, this Chinese poultry lineage contained more codons inferred to be under positive selection, including at known antigenic sites, and its rates of nonsynonymous divergence and adaptative fixation increased after mass poultry vaccination began. Our results indicate that the epidemiological, ecological and evolutionary consequences of widespread AIV vaccination in poultry may be linked in complex ways, and that much work is needed to better understand how such interventions may affect AIV transmission to, within and from wild birds.

evolutionary biology↗

bioRxiv2023

Revisiting the origins of the Sobemovirus genus: a case for ancient origins of plant viruses

The discrepancy between short- and long-term rate estimates, known as the time-dependent rate phenomenon (TDRP), poses a challenge to extrapolating evolutionary rates over time and reconstructing evolutionary history of viruses. The TDRP reveals a decline in evolutionary rate estimates with the measurement timescale, explained empirically by a power-law rate decay, notably observed in animal and human viruses. A mechanistic evolutionary model, the Prisoner of War (PoW) model, has been proposed to address TDRP in viruses. Although TDRP has been studied in animal viruses, its impact on plant virus evolutionary history remains largely unexplored. Here, we investigated the consequences of TDRP in plant viruses by applying the PoW model to reconstruct the evolutionary history of sobemoviruses, plant pathogens with significant importance due to their impact on agriculture and plant health. Our analysis showed that the Sobemovirus genus dates back over four million years, indicating an ancient origin. We found evidence that supports deep host jumps to Poaceae, Fabaceae, and Solanaceae occurring between tens to hundreds of thousand years ago, followed by specialization. Remarkably, the TDRP-corrected evolutionary history of sobemoviruses was extended far beyond previous estimates that had suggested their emergence during the Neolithic period. By incorporating sequences collected through metagenomic analyses, the resulting phylogenetic tree showcases increased genetic diversity, reflecting a deep history of sobemovirus species with major radiation events taking place during the Neolithic period, suggesting rapid diversification in that period. Our findings make a case for the possibility of deep evolutionary origins of plant viruses.

evolutionary biology↗

bioRxiv2023

Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic

Zoonotic spillovers of viruses have occurred through the animal trade worldwide. The start of the COVID-19 pandemic was traced epidemiologically to the Huanan Wholesale Seafood Market, the site with the most reported wildlife vendors in the city of Wuhan, China. Here, we analyze publicly available qPCR and sequencing data from environmental samples collected in the Huanan market in early 2020. We demonstrate that the SARS-CoV-2 genetic diversity linked to this market is consistent with market emergence, and find increased SARS-CoV-2 positivity near and within a particular wildlife stall. We identify wildlife DNA in all SARS-CoV-2 positive samples from this stall. This includes species such as civets, bamboo rats, porcupines, hedgehogs, and one species, raccoon dogs, known to be capable of SARS-CoV-2 transmission. We also detect other animal viruses that infect raccoon dogs, civets, and bamboo rats. Combining metagenomic and phylogenetic approaches, we recover genotypes of market animals and compare them to those from other markets. This analysis provides the genetic basis for a short list of potential intermediate hosts of SARS-CoV-2 to prioritize for retrospective serological testing and viral sampling.

genomics↗

bioRxiv2023

The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2

The emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 has led to increased sampling of related sarbecoviruses circulating primarily in horseshoe bats. These viruses undergo frequent recombination and exhibit spatial structuring across Asia. Employing recombination-aware phylogenetic inference on bat sarbecoviruses, we find that the closest-inferred bat virus ancestors of SARS-CoV and SARS-CoV-2 existed just [~]1-3 years prior to their emergence in humans. Phylogeographic analyses examining the movement of related sarbecoviruses demonstrate that they traveled at similar rates to their horseshoe bat hosts and have been circulating for thousands of years in Asia. The closest-inferred bat virus ancestor of SARS-CoV likely circulated in western China, and that of SARS-CoV-2 likely circulated in a region comprising southwest China and northern Laos, both a substantial distance from where they emerged. This distance and recency indicate that the direct ancestors of SARS-CoV and SARS-CoV-2 could not have reached their respective sites of emergence via the bat reservoir alone. Our recombination-aware dating and phylogeographic analyses reveal a more accurate inference of evolutionary history than performing only whole-genome or single gene analyses. These results can guide future sampling efforts and demonstrate that viral genomic fragments extremely closely related to SARS-CoV and SARS-CoV-2 were circulating in horseshoe bats, confirming their importance as the reservoir species for SARS viruses.

evolutionary biology↗

bioRxiv2023

The evolutionary history of hepaciviruses

In the search for natural reservoirs of hepatitis C virus (HCV), a broad diversity of non-human viruses within the Hepacivirus genus has been uncovered. However, the evolutionary dynamics that shaped the diversity and timescale of hepaciviruses evolution remain elusive. To gain further insights into the origins and evolution of this genus, we screened a large dataset of wild mammal samples (n = 1,672) from Africa and Asia, and generated 34 full-length hepacivirus genomes. Phylogenetic analysis of these data together with publicly available genomes emphasizes the importance of rodents as hepacivirus hosts and we identify 13 rodent species and 3 rodent genera (in Cricetidae and Muridae families) as novel hosts of hepaciviruses. Through co-phylogenetic analyses, we demonstrate that hepacivirus diversity has been affected by cross-species transmission events against the backdrop of detectable signal of virus-host co-divergence in the deep evolutionary history. Using a Bayesian phylogenetic multidimensional scaling approach, we explore the extent to which host relatedness and geographic distances have structured present-day hepacivirus diversity. Our results provide evidence for a substantial structuring of mammalian hepacivirus diversity by host as well as geography, with a somewhat more irregular diffusion process in geographic space. Finally, using a mechanistic model that accounts for substitution saturation, we provide the first formal estimates of the timescale of hepacivirus evolution and estimate the origin of the genus to be about 22 million years ago. Our results offer a comprehensive overview of the micro- and macroevolutionary processes that have shaped hepacivirus diversity and enhance our understanding of the long-term evolution of the Hepacivirus genus. SignificanceSince the discovery of Hepatitis C virus, the search for animal virus homologues has gained significant traction, opening up new opportunities to study their origins and long-term evolutionary dynamics. Capitalizing on a large-scale screening of wild mammals, and genomic sequencing, we expand the novel rodent host range of hepaciviruses and document further virus diversity. We infer a significant influence of frequent cross-species transmission as well as some signal for virus-host co-divergence, and find comparative host and geographic structure. We also provide the first formal estimates of the timescale of hepaciviruses indicating an origin of about 22 million years ago. Our study offers new insights in hepacivirus evolutionary dynamics with broadly applicable methods that can support future research in virus evolution.

microbiology↗

bioRxiv2023

Synchrony of Bird Migration with Avian Influenza Global Spread; Implications for Vulnerable Bird Orders

Highly pathogenic avian influenza virus (HPAIV) A H5 clade 2.3.4.4 has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, it is unclear how seasonal bird migration facilitates global virus dispersal, and which avian species are exposed to HPAI H5 clade 2.3.4.4 viruses and where. To shed light on ongoing global outbreaks, we sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences. First, based on viral phylogeography and bird migration networks, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing vulnerable bird orders at geographical origins and destinations of HPAIV H5 lineage movements. Notably, we highlight the potential importance of relatively under-discussed Suliformes and Ciconiiformes, in addition to Anseriformes and Charadriiformes, in virus lineage movements. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behaviour and life history in avian influenza studies.

ecology↗

bioRxiv2023

Parasite hybridization promotes spreading of endosymbiotic viruses

Viruses are the most abundant biological entities on Earth and play a significant role in the evolution of many organisms and ecosystems. In pathogenic protozoa, the presence of endosymbiotic viruses has been linked to an increased risk of treatment failure and severe clinical outcome. Here, we studied the molecular epidemiology of the zoonotic disease cutaneous leishmaniasis in Peru and Bolivia through a joint evolutionary analysis of Leishmania braziliensis parasites and their endosymbiotic Leishmania RNA virus. We show that parasite populations circulate in isolated pockets of suitable habitat and are associated with single viral lineages that appear in low prevalence. In contrast, groups of hybrid parasites were geographically and ecologically dispersed, and commonly infected from a pool of genetically diverse viruses. Our results suggest that parasite hybridization, likely due to increased human migration and ecological perturbations, increased the frequency of endosymbiotic interactions known to play a key role in disease severity.

evolutionary biology↗

bioRxiv2023

Putative APOBEC3 deaminase editing in MPXV as evidence for sustained human transmission since at least 2016.

Mpox is often described as being endemic in West and Central Africa as a zoonotic disease that transmits through contact with the reservoir rodent host, likely a species of African squirrel. In May 2022, human cases of Mpox were detected spreading internationally beyond countries with known endemic reservoirs. At time of writing, 84,700 confirmed cases have been reported in 110 countries. When the first cases from 2022 were sequenced, it was seen that they shared 42 single nucleotide differences from the closest mpox virus (MPXV) genome sampled in 2018. This number of changes within 3-4 years is unexpectedly large and points to a much greater evolutionary rate than expected for a poxvirus. Strikingly, most nucleotide changes are of a specific type - a dinucleotide change from TC->TT or its reverse complement GA->AA. This mutation type is characteristic of the action of APOBEC3 deaminases; host-enzymes with reported antiviral function. Analysis of MPXV genomes sampled from 2017 to 2022 showed further evidence of TC->TT mutation pattern enrichment, with 93% of transmitted single nucleotide mutations since 2017 consistent with APOBEC3 editing. Assuming APOBEC-editing is characteristic of MPXV infection in human hosts, we propose an APOBEC clock that - at a rate of ~6 APOBEC3 mutations per year - estimates MPXV has been circulating in humans since 2016. This evolutionary pattern of host-enzyme editing has implications for the longer-term fitness of the virus in this epidemic as such mechanisms are primarily antiviral in function, but in the context of a poxvirus also provide a source of variation that may conceivably facilitate adaptation.

evolutionary biology↗

bioRxiv2022

Evolution of influenza A virus hemagglutinin H1 and H3 across host species

The Influenza A virus (IAV) hemagglutinin protein (HA) has been studied extensively, but its evolution has not been thoroughly compared among major host species. We compared H3 and H1 evolutionary rates among 49 lineages differentiated by host (avian, canine, equine, human, swine), phylogeny, and geography. Rates of nonsynonymous evolution, relative to synonymous rates, were higher in mammalian than avian hosts. Human seasonal HA and classical swine H1 accumulated 11-13 glycosylation sites, primarily in the antigenically important head domain, whereas lower numbers were maintained in other hosts. Canines had the highest ratio of nonsynonymous to synonymous changes in the more conserved stalk domain. Amino acid changes in canine viruses occurred disproportionately at residues located at protein interfaces. This suggests that they were adaptations affecting the major structural rearrangement of HA, which is critical for cell entry. These findings invite further study of how host ecology and physiology affect natural selection. AUTHOR SUMMARYInfluenza virus evolution is of practical importance to health in addition to being an excellent system for the study of parasite/host evolution. Our work explores a largely untapped aspect of influenza evolution: sequence evolution in non-human hosts. This is important in its own right, in terms of both science and domestic animal health. It also puts the evolution of human influenza in a larger, comparative context. Our results also provide evidence concerning the evolution of the hemagglutinin stem domain, which has not been a focus of study but has new importance due to the development of stem-based universal influenza vaccines.

evolutionary biology↗

bioRxiv2022

Discovery of Flaviviridae-derived endogenous viral elements in shrew genomes provide novel insights into Pestivirus ancient history

As viral genomic imprints in host genomes, endogenous viral elements (EVEs) shed light on the deep evolutionary history of viruses, ancestral host ranges, and ancient viral-host interactions. In addition, they may provide crucial information for calibrating viral evolutionary timescales. In this study, we conducted a comprehensive in silico screening of a large dataset of available mammalian genomes for EVEs deriving from members of the viral family Flaviviridae, an important group of viruses including well-known human pathogens. We identified two novel pestivirus-like EVEs in the reference genome of the Indochinese shrew (Crocidura indochinensis). Homologs of these novel EVEs were subsequently detected in vivo by molecular detection and sequencing in 27 shrew species, including 26 species representing a wide distribution within the Crocidurinae subfamily and one in the Soricinae subfamily. Based on this wide distribution, we estimate that the integration event occurred before the last common ancestor of the subfamily, about 10.8 million years ago, attesting to an ancient origin of pestiviruses and Flaviviridae in general. Moreover, we provide the first description of Flaviviridae-derived EVEs in mammals even though the family encompasses numerous mammal-infecting members, including major human pathogens such as Zika, dengue, or hepatitis C viruses. This also suggests that shrews were past and perhaps also current natural reservoirs of pestiviruses. Taken together, our results expand the current known Pestivirus host range and provide novel insight into the ancient evolutionary history of pestiviruses and the Flaviviridae family in general.

microbiology↗

bioRxiv2022

Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function

Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.

evolutionary biology↗

bioRxiv2021

Full protection against all four SARS-CoV-2 variants of concern (VOC) in hamsters requires revision of spike antigen used for vaccination.

Current first-generation COVID-19 vaccines are based on prototypic spike sequences from ancestral 2019 SARS-CoV-2 strains. However, the ongoing pandemic is fueled by variants of concern (VOC) that threaten to escape vaccine-mediated protection. Here we show in a stringent hamster model that immunization using prototypic spike expressed from a potent YF17D viral vector (1) provides vigorous protection against infection with ancestral virus (B lineage) and VOC Alpha (B.1.1.7), however, is insufficient to provide maximum protection against the Beta (B.1.351) variant. To improve vaccine efficacy, we created a revised vaccine candidate that carries an evolved spike antigen. Vaccination of hamsters with this updated vaccine candidate provides full protection against intranasal challenge with all four VOCs Alpha, Beta, Gamma (P.1) and Delta (B.1.617.2) resulting in complete elimination of infectious virus from the lungs and a marked improvement in lung pathology. Vaccinated hamsters did also no longer transmit the Delta variant to non-vaccinated sentinels. Hamsters immunized with our modified vaccine candidate also mounted marked neutralizing antibody responses against the recently emerged Omicron (B.1.1.529) variant, whereas the old vaccine employing prototypic spike failed to induce immunity to this antigenically distant virus. Overall, our data indicate that current first-generation COVID-19 vaccines need to be urgently updated to cover newly emerging VOCs to maintain vaccine efficacy and to impede virus spread at the community level. Significance StatementSARS-CoV-2 keeps mutating rapidly, and the ongoing COVID-19 pandemic is fueled by new variants escaping immunity induced by current first-generation vaccines. There is hence an urgent need for universal vaccines that cover variants of concern (VOC). In this paper we show that an adapted version of our vaccine candidate YF-S0* provides full protection from infection, virus transmission and disease by VOCs Alpha, Beta, Gamma and Delta, and also results in markedly increased levels of neutralizing antibodies against recently emerged Omicron VOC in a stringent hamster model. Our findings underline the necessity to update COVID-19 vaccines to curb the pandemic, providing experimental proof on how to maintain vaccine efficacy in view of an evolving SARS-CoV-2 diversity.

microbiology↗

bioRxiv2021

Total virome characterizations of game animals in China reveals a spectrum of emerging viral pathogens

Game animals are wildlife species often traded and consumed as exotic food, and are potential reservoirs for SARS-CoV and SARS-CoV-2. We performed a meta-transcriptomic analysis of 1725 game animals, representing 16 species and five mammalian orders, sampled across China. From this we identified 71 mammalian viruses, with 45 described for the first time. Eighteen viruses were considered as potentially high risk to humans and domestic animals. Civets (Paguma larvata) carried the highest number of potentially high risk viruses. We identified the transmission of Bat coronavirus HKU8 from a bat to a civet, as well as cross-species jumps of coronaviruses from bats to hedgehogs and from birds to porcupines. We similarly identified avian Influenza A virus H9N2 in civets and Asian badgers, with the latter displaying respiratory symptoms, as well as cases of likely human-to-wildlife virus transmission. These data highlight the importance of game animals as potential drivers of disease emergence. HighlightsO_LI1725 game animals from five mammalian orders were surveyed for viruses C_LIO_LI71 mammalian viruses were discovered, 18 with a potential risk to humans C_LIO_LICivets harbored the highest number of potential high risk viruses C_LIO_LIA species jump of an alphacoronavirus from bats to a civet was identified C_LIO_LIH9N2 influenza virus was detected in a civet and an Asian badger C_LIO_LIHumans viruses were also identified in game animals C_LI

zoology↗

bioRxiv2021

Spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Competitive interactions between pathogen strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures, however, this has rarely been measured due to inadequate data and analytical tools. Bordetella pertussis (B. pertussis), responsible for 160,000 deaths annually1, provides a rare natural experiment as many countries have switched from whole cell vaccines to acellular vaccines, which have very different immunogenic properties2,3. Here we use 3,344 sequences from 23 countries and build phylogenetic models to reveal that B. pertussis has substantial diversity within communities, with the relative fitness of local genotypes changing in response to switches in vaccine policy. We demonstrate that the number of transmission chains circulating within subnational regions is strongly associated with host population size. It takes 5-10 years for individual lineages to be homogeneously distributed throughout Europe or the United States. Increased fitness of pertactin-deficient strains following implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of national vaccine policies in shifting local diversity of a pathogen that still poses a large burden on global public health.

genetics↗

bioRxiv2021

Predicting the evolution of Lassa Virus endemic area and population at risk over the next decades

Lassa fever is listed among the diseases that pose the greatest risks to public health by the World Health Organization. This severe viral hemorrhagic fever is caused by Lassa virus, a zoonotic pathogen that repeatedly spills over to humans from its rodent reservoirs. It is currently not known how climate change, transformations in land use, and human population growth could affect the endemic area of this virus, currently limited to parts of West Africa. By exploring the environmental data associated with virus occurrence, we show how temperature, precipitation and the presence of pastures determine ecological suitability for virus circulation. We project that regions in Central and East Africa will likely become suitable for Lassa virus over the next decades and estimate that the total population living in areas suitable for Lassa virus may grow from about 100 million to 700 million by 2070. By analysing geotagged viral genomes, we find that in the event of Lassa virus being introduced into a new suitable region, its spread might remain spatially limited over the first decades. Our results highlight how the endemic area of Lassa virus may expand well beyond West Africa in the next decades due to human impact on the environment, putting hundreds of million more people at risk of infection.

microbiology↗