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Strengthened in-country sequencing generated 28 Lassa virus genomes from human clinical cases in Guinea, expanding knowledge of Lassa fever in the country. Phylogeographic analysis revealed cross-border exchange between Liberia and the N'Zérékoré region and a Sierra Leone introduction into Guéckédou. Enhanced genomic surveillance is crucial to guide public health.

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.

Lassa fever, caused by the Lassa virus (LASV), is a deadly disease characterized by hemorrhages. Annually, it affects approximately 300,000 people in West Africa and causes about 5,000 deaths. It currently has no approved vaccine and is categorized as a top-priority disease. Apart from its endemicity to West Africa, there have been exported cases in almost all continents, including several European countries. Distinct Lassa virus lineages circulate in specific regions, and have been reported to show varying immunological behaviors and may contribute to differing disease outcomes. It is therefore important to rapidly identify which lineage caused an outbreak or an exported case. We present CLASV, a machine learning-based lineage assignment tool built using a Random Forest classifier. CLASV processes raw nucleotide sequences and assigns them to the dominant circulating lineages (II, III, and IV/V) rapidly and accurately. CLASV is implemented in Python for ease of integration into existing workflows and is freely available for public use.

Lassa virus (LASV), which causes considerable morbidity and mortality annually, has a high genetic diversity across West Africa. LASV glycoprotein (GP) expresses this diversity, but most LASV vaccine candidates utilize only the Lineage IV LASV Josiah strain GP antigen as an immunogen and homologous challenge with Lineage IV LASV. In addition to the sequence variation amongst the LASV lineages, these lineages are also distinguished in their presentations. Inter-lineage variations within previously mapped B-cell and T-cell LASV GP epitopes and the breadth of protection in LASV vaccine/challenge studies were examined critically. Multiple alignments of the GP primary sequence of strains from each LASV lineage showed that LASV GP has diverging degrees of amino acid conservation within known epitopes among LASV lineages. Conformational B-cell epitopes spanning different sites in GP subunits were less impacted by LASV diversity. LASV GP diversity should influence the approach used for LASV vaccine design. Expression of LASV GP on viral vectors, especially in its prefusion configuration, has shown potential for protective LASV vaccines that can overcome LASV diversity. Advanced vaccine candidates should demonstrate efficacy against all LASV lineages for evidence of a pan-LASV vaccine.

Lassa virus (LASV), a zoonotic, bi-segmented arenavirus endemic to West Africa, causes seasonal epidemics with substantial morbidity and mortality. Increasing frequency of exported cases emphasizes the need for near real-time genomic surveillance to support outbreak response and clinical decision-making. We developed a suite of open-access resources on the Nextstrain and Nextclade platforms tailored to LASV. These include live phylogenetic and phylogeographic visualization, as well as Nextclade builds for rapid mutation detection and lineage assignment based on the L and S segments and the glycoprotein complex (GPC). A dedicated GPC phylogeny enables tracking of clinically relevant mutations, including immunologically relevant variants such as alanine at position 76 (A76), which is prevalent in lineage II and is implicated in reduced binding of monoclonal antibody 25.10C. The Nextclade tools distinguish LASV from other mammarenaviruses and assign lineages with Matthews correlation coefficients exceeding 85%. These tools are available at https://nextstrain.org/lassa for immediate use in surveillance, data annotation, outbreak response, and potentially support clinical decision-making in both endemic regions and exported-case scenarios. A key limitation is dependence on genomic data quality and recency. Although sampling-to-submission delays have decreased over the past 40 years, the average delay in the past five years remains ∼2 years. In many endemic LASV regions, challenges, such as limited resources, infrastructure, and previous experiences of stigmatization and political repercussions linked to outbreak reporting, restrict data sharing. The resulting disparities and delays may hinder comprehensive surveillance and timely response, with implications for global public health.

Lassa virus (LASV) is endemic in parts of West Africa where it causes Lassa fever (LF), a viral hemorrhagic fever with frequent fatal outcomes. The diverse LASV strains are grouped into six major lineages based on the geographical location of the isolated strains. In this study, we have focused on the lineage II strains from southern Nigeria. We determined the viral sequences from positive cases of LF reported at tertiary hospitals in Ebonyi and Enugu between 2012 and 2016. Reverse transcription-polymerase chain reaction (RT-PCR) showed that 29 out of 123 suspected cases were positive for the virus among which 11 viral gene sequences were determined. Phylogenetic analysis of the complete coding sequences of the four viral proteins revealed that lineage II strains are broadly divided into two genetic clades that diverged from a common ancestor 195 years ago. One clade, consisting of strains from Ebonyi and Enugu, was more conserved than the other from Irrua, although the four viral proteins were evolving at similar rates in both clades. These results suggested that the viruses of these clades have been distinctively evolving in geographically separate parts of southern Nigeria. Furthermore, the epidemiological data of the 2014 outbreak highlighted the role of human-to-human transmission in this outbreak, which was supported by phylogenetic analysis showing that 13 of the 16 sequences clustered together. These results provide new insights into the evolution of LASV in southern Nigeria and have important implications for vaccine development, diagnostic assay design, and LF outbreak management.

Mammarenaviruses include several known human pathogens, such as the prototypic lymphocytic choriomeningitis virus (LCMV) that can cause neurological diseases and Lassa virus (LASV) that causes endemic hemorrhagic fever infection. LASV-infected patients show diverse clinical manifestations ranging from asymptomatic infection to hemorrhage, multi-organ failures and death, the mechanisms of which have not been well characterized. We have previously shown that the matrix protein Z of pathogenic arenaviruses, including LASV and LCMV, can strongly inhibit the ability of the innate immune protein RIG-I to suppress type I interferon (IFN-I) expression, which serves as a mechanism of viral immune evasion and virulence. Here, we show that Z proteins of diverse LASV isolates derived from rodents and humans have a high degree of sequence variations at their N- and C-terminal regions and produce variable degrees of inhibition of human RIG-I (hRIG-I) function in an established IFN-β promoter-driven luciferase (LUC) reporter assay. Additionally, we show that Z proteins of four known LCMV strains can also inhibit hRIG-I at variable degrees of efficiency. Collectively, our results confirm that Z proteins of pathogenic LASV and LCMV can inhibit hRIG-I and suggest that strain variations of the Z proteins can influence their efficiency to suppress host innate immunity that might contribute to viral virulence and disease heterogeneity.

Lassa mammarenavirus (LASV) is the etiologic agent of Lassa fever. In endemic regions in West Africa, LASV genetic diversity tends to cluster by geographic area. Seven LASV lineages are recognized, but the role of viral genetic determinants on disease presentation in humans is uncertain. We investigated the geographic structure and distribution of LASV in West Africa. We found strong spatial clustering of LASV populations, with two major east–west and north–south diversity gradients. Analysis of ancestry components indicated that known LASV lineages diverged from an ancestral population that most likely circulated in Nigeria, although alternative locations, such as Togo, cannot be excluded. Extant sequences carrying the largest contribution of this ancestral population include the prototype Pinneo strain, the Togo isolates, and a few viruses isolated in Nigeria. The LASV populations that experienced the strongest drift circulate in Mali and the Ivory Coast. By focusing on sequences form a single LASV sublineage (IIg), we identified an ancestry component possibly associated with protection from a fatal disease outcome. Although the same ancestry component tends to associate with lower viral loads in plasma, the small sample size requires that these results are treated with extreme caution.

Lassa fever is an acute viral illness characterized by multi-organ failure and hemorrhagic manifestations. Lassa fever is most frequently diagnosed in Nigeria, Sierra Leone, Liberia, and Guinea, although sporadic cases have been recorded in other West African countries, including Mali. The etiological agent of Lassa fever is Lassa virus (LASV), an Arenavirus which is maintained in nature and frequently transmitted to humans by Mastomys natalensis. The purpose of this study was to better define the geographic distribution of LASV-infected rodents in sub-Saharan Mali. Small mammals were live-trapped at various locations across Mali for the purpose of identifying potential zoonotic pathogens. Serological and molecular assays were employed and determined LASV infected rodents were exclusively found in the southern Mali near the border of Côte d'Ivoire. Overall, 19.4% of Mastomys natalensis sampled in this region had evidence of LASV infection, with prevalence rates for individual villages ranging from 0 to 52%. Full-length genomic sequences were determined using high throughput sequencing methodologies for LASV isolates generated from tissue samples of rodents collected in four villages and confirmed the phylogenetic clustering of Malian LASV with strain AV. The risk of human infections with LASV is greatest in villages in southern Mali. Lassa fever should be considered in the differential diagnosis for febrile individuals and appropriate diagnostic techniques need to be established to determine the incidence of infection and disease in these regions.

This study aimed at reconstructing the spatial and temporal evolution of Lassa virus (LASV) in the natural host population. To this end, we generated 132 partial nucleoprotein sequences of LASV from M. natalensis trapped in 12 villages around Faranah, Upper Guinea, over a period of 12 years. This study reveals two main features of LASV evolution in M. natalensis . First, the virus evolves in the reservoir with a molecular clock rate of 9 (7–11) × 10 –4 position –1 year –1 implying that contemporary LASV lineages circulate in the Faranah area since less than 100 years. Second, viruses circulating in a specific village are diverse and polyphyletic. We observed, however, there are monophyletic clusters at village and sub-village level at specific points in time. In conclusion, our data indicate that the temporal and spatial pattern of LASV evolution in the natural reservoir is characterized by a combination of stationary circulation within a village and virus movement between villages. The latter feature is relevant for rodent control strategies, as it implies that recurrence of the virus from neighbouring villages may occur in villages where the virus has previously been eradicated.