New Lineage of Lassa Virus, Togo, 2016.
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ABSTRACT:
SUBMITTER: Whitmer SLM
PROVIDER: S-EPMC5823357 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We report two outbreaks of Lassa fever that occurred in Benin in 2014 and 2016 with 20 confirmed cases and 50% (10/20) mortality. Benin was not previously considered to be an endemic country for Lassa fever, resulting in a delay to diagnose the disease and its human transmission. Molecular investigations showed the viral genomes to be similar to that of the Togo strain, which is genetically very different from other known strains and confirms the existence of a new lineage. Endemic circulation of Lassa virus in a new territory and the genetic diversity thus confirm that this virus represents a growing threat for West African people. Given the divergence of the Benin strain from the prototypic Josiah Sierra Leone strain frequently used to generate vaccine candidates, the efficacy of vaccine candidates should also be demonstrated with this strain.
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Project description: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.
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Project description:Lassa virus has been identified in 3 pygmy mice, Mus baoulei, in central Benin. The glycoprotein and nucleoprotein sequences cluster with the Togo strain. These mice may be a new reservoir for Lassa virus in Ghana, Togo, and Benin.
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Project description:We describe the isolation and characterization of a new Lassa virus strain imported into Germany by a traveler who had visited Ghana, Côte D'Ivoire, and Burkina Faso. This strain, designated "AV," originated from a region in West Africa where Lassa fever has not been reported. Viral S RNA isolated from the patient's serum was amplified and sequenced. A long-range reverse transcription polymerase chain reaction allowed amplification of the full-length (3.4 kb) S RNA. The coding sequences of strain AV differed from those of all known Lassa prototype strains (Josiah, Nigeria, and LP) by approximately 20%, mainly at third codon positions. Phylogenetically, strain AV appears to be most closely related to strain Josiah from Sierra Leone. Lassa viruses comprise a group of genetically highly diverse strains, which has implications for vaccine development. The new method for full-length S RNA amplification may facilitate identification and molecular analysis of new arenaviruses or arenavirus strains.
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Project description: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.
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Project description:BackgroundThe changing epidemiology of the Lassa virus from endemic areas to other parts of West Africa has been reported. However, there have been no documented Lassa fever transmission chains in the Benin Republic. Two outbreaks of Lassa fever (November 2014 and January 2016) in the Benin Republic were characterised by a high number of deaths (more than 50%) among 27 confirmed and other unconfirmed cases.ObjectivesWe report the detection, confirmation and relatedness of the Lassa virus strains from the Benin Republic with other isolates within the West African Sub-region.MethodsA total of 70 blood samples (16 from 2014 and 54 from 2016) from suspected cases with signs and symptoms suggestive of viral haemorrhagic fever were received for molecular analysis at the Centre for Human and Zoonotic Virology, College of Medicine, University of Lagos and the Lagos University Teaching Hospital. With the detection of the Lassa virus RNA by reverse transcriptase polymerase chain reaction, sequencing and phylogenetic analyses were performed using the Sanger dideoxy sequencing technology platform and the MEGA6 software.ResultsS segments of the Lassa virus RNA genome were detected in 5 (7.1%) of the 70 samples analysed. Sequencing and a phylogenetic tree construction confirmed that the strain of Lassa virus had close relationships with strains previously isolated from Nigeria.ConclusionWe confirmed the presence of the Lassa virus in the Benin Republic, with 2 strains having molecular epidemiological links with Lineage I and II strains from Nigeria. To reduce the likelihood of outbreaks, there is a need for heightened awareness and strengthened surveillance systems about Lassa fever, particularly in the sub-region.
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Project description:Deep mutational scanning of the Lassa virus Josiah strain glycoprotein complex (GPC)
| PRJNA1071644 | ENA
Project description: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.
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Project description:Previous imported cases of Lassa fever (LF) into the United Kingdom from the Ivory Coast and Mali, as well as the detection of Lassa virus (LASV) among the Mastomys natalensis population within Mali has led to the suggestion that the endemic area for LF is expanding. Initial phylogenetic analyses arrange isolates from Mali and the Ivory Coast separately from the classical lineage IV isolates taken from Sierra Leone, Guinea, and Liberia. The availability of full genome sequences continues to increase, allowing for a more complete phylogenetic comparison of the isolates from Mali and the Ivory Coast to the other existing isolates. In this study, we utilized a Bayesian approach to infer the demographic histories of each LASV isolate for which the full sequence was available. Our results indicate that the isolates from Mali and the Ivory Coast group separately from the isolates of lineage IV, comprising a distinct fifth lineage. The split between lineages IV and V is estimated to have occurred around 200-300 years ago, which coincides with the colonial period of West Africa.
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Project description:The cell entry and humoral immune response of the human pathogen Lassa virus (LV), a biosafety level 4 (BSL4) Old World arenavirus, are not well characterized. LV pseudoparticles (LVpp) are a surrogate model system that has been used to decipher factors and routes involved in LV cell entry under BSL2 conditions. Here, we describe LVpp, which are highly infectious, with titers approaching those obtained with pseudoparticles displaying G protein of vesicular stomatitis virus and their the use for the characterization of LV cell entry and neutralization. Upon cell attachment, LVpp utilize endocytic vesicles for cell entry as described for many pH-dependent viruses. However, the fusion of the LV glycoproteins is activated at unusually low pH values, with optimal fusion occurring between pH 4.5 and 3, a pH range at which fusion characteristics of viral glycoproteins have so far remained largely unexplored. Consistent with a shifted pH optimum for fusion activation, we found wild-type LV and LVpp to display a remarkable resistance to exposure to low pH. Finally, LVpp allow the fast and quantifiable detection of neutralizing antibodies in human and animal sera and will thus facilitate the study of the humoral immune response in LV infections.
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