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Nature Reviews. Microbiology Feb 2023Lassa virus (LASV) is endemic in the rodent populations of Sierra Leone, Nigeria and other countries in West Africa. Spillover to humans occurs frequently and results in... (Review)
Review
Lassa virus (LASV) is endemic in the rodent populations of Sierra Leone, Nigeria and other countries in West Africa. Spillover to humans occurs frequently and results in Lassa fever, a viral haemorrhagic fever (VHF) associated with a high case fatality rate. Despite advances, fundamental gaps in knowledge of the immunology, epidemiology, ecology and pathogenesis of Lassa fever persist. More frequent outbreaks, the potential for further geographic expansion of Mastomys natalensis and other rodent reservoirs, the ease of procurement and possible use and weaponization of LASV, the frequent importation of LASV to North America and Europe, and the emergence of novel LASV strains in densely populated West Africa have driven new initiatives to develop countermeasures for LASV. Although promising candidates are being evaluated, as yet there are no approved vaccines or therapeutics for human use. This Review discusses the virology of LASV, the clinical course of Lassa fever and the progress towards developing medical countermeasures.
Topics: Humans; Lassa Fever; Lassa virus; Africa, Western; Viral Vaccines
PubMed: 36097163
DOI: 10.1038/s41579-022-00789-8 -
Oncotarget Oct 2015
Topics: Arenaviridae Infections; Arenavirus; Exoribonucleases; Host-Pathogen Interactions; Humans; Interferon Type I; Viral Proteins
PubMed: 26468986
DOI: 10.18632/oncotarget.6110 -
Microorganisms Apr 2021Lassa fever causes an approximate 5000 to 10,000 deaths annually in West Africa and cases have been imported into Europe and the Americas, challenging public health.... (Review)
Review
Lassa fever causes an approximate 5000 to 10,000 deaths annually in West Africa and cases have been imported into Europe and the Americas, challenging public health. Although Lassa virus was first described over 5 decades ago in 1969, no treatments or vaccines have been approved to treat or prevent infection. In this review, we discuss current therapeutics in the development pipeline for the treatment of Lassa fever, focusing on those that have been evaluated in humans or animal models. Several treatments, including the antiviral favipiravir and a human monoclonal antibody cocktail, have shown efficacy in preclinical rodent and non-human primate animal models and have potential for use in clinical settings. Movement of the promising preclinical treatment options for Lassa fever into clinical trials is critical to continue addressing this neglected tropical disease.
PubMed: 33917071
DOI: 10.3390/microorganisms9040772 -
Viruses Apr 2021Rodent-borne arenaviruses have been traditionally predominantly associated with certain muroid species from genera (African arenaviruses) or with species that belong to...
Rodent-borne arenaviruses have been traditionally predominantly associated with certain muroid species from genera (African arenaviruses) or with species that belong to murid subfamily (New World arenaviruses) [...].
Topics: Amino Acid Sequence; Animals; Arenaviridae Infections; Arenavirus; Fishes; Humans; Rodentia; Snakes
PubMed: 33919632
DOI: 10.3390/v13040703 -
Pathogens (Basel, Switzerland) Mar 2020Lassa virus (LASV), the causative agent of Lassa fever, is estimated to be responsible for up to 300,000 new infections and 5000 deaths each year across Western Africa.... (Review)
Review
Lassa virus (LASV), the causative agent of Lassa fever, is estimated to be responsible for up to 300,000 new infections and 5000 deaths each year across Western Africa. The most recent 2018 and 2019 Nigerian outbreaks featured alarmingly high fatality rates of up to 25.4%. In addition to the severity and high fatality of the disease, a significant population of survivors suffer from long-term sequelae, such as sensorineural hearing loss, resulting in a huge socioeconomic burden in endemic regions. There are no Food and Drug Administration (FDA)-approved vaccines, and therapeutics remain extremely limited for Lassa fever. Development of countermeasures depends on relevant animal models that can develop a disease strongly mimicking the pathogenic features of Lassa fever in humans. The objective of this review is to evaluate the currently available animal models for LASV infection with an emphasis on their pathogenic and histologic characteristics as well as recent advances in the development of a suitable rodent model. This information may facilitate the development of an improved animal model for understanding disease pathogenesis of Lassa fever and for vaccine or antiviral testing.
PubMed: 32155851
DOI: 10.3390/pathogens9030197 -
Cell Host & Microbe Dec 2022The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been...
The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation. These GPC nanoparticles present twenty prefusion GPC trimers on the surface of an icosahedral particle. Cryo-EM studies of GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against the lethal Lassa virus challenge in guinea pigs. Additionally, we isolated a neutralizing antibody that mapped to the putative receptor-binding site, revealing a previously undefined site of vulnerability. Collectively, these findings offer potential approaches to vaccine and therapeutic design for the Lassa virus.
Topics: Guinea Pigs; Rabbits; Animals; Lassa virus; Antibodies, Neutralizing; Lassa Fever; Glycoproteins; Vaccines, Synthetic; Nanoparticles
PubMed: 36400021
DOI: 10.1016/j.chom.2022.10.018 -
Journal of Clinical Microbiology Jun 2017Lassa virus remains an important cause of illness in West Africa and among the travelers returning from this region with an acute febrile illness. The symptoms of Lassa... (Review)
Review
Lassa virus remains an important cause of illness in West Africa and among the travelers returning from this region with an acute febrile illness. The symptoms of Lassa fever can be nonspecific and mimic those of other endemic infections, especially early in illness, making a clinical diagnosis difficult; therefore, laboratory testing is needed to confirm the diagnosis. An early identification of Lassa fever is crucial for maximizing the benefit of available antiviral therapy, as treatment efficacy rapidly decreases following the clinical onset of the disease. This minireview provides an overview of the currently available diagnostic tests for Lassa fever and their strengths and weaknesses.
Topics: Africa, Western; Clinical Laboratory Techniques; Diagnostic Tests, Routine; Humans; Lassa Fever; Lassa virus
PubMed: 28404674
DOI: 10.1128/JCM.00170-17 -
Biotechnology and Bioengineering Mar 2021Lack of experimental human models hinders research on Lassa hemorrhagic fever and the development of treatment strategies. Here, we report the first chip-based model for...
Lack of experimental human models hinders research on Lassa hemorrhagic fever and the development of treatment strategies. Here, we report the first chip-based model for Lassa hemorrhagic syndrome. The chip features a microvessel interfacing collagen network as a simple mimic for extracellular matrix, allowing for quantitative and real-time vascular integrity assessment. Luminal infusion of Lassa virus-like particles led to a dramatic increase in vascular permeability in a viral load-dependent manner. Using this platform, we showed that Fibrin-derived peptide FX06 can be used to suppress the vascular integrity loss. This simple chip-based model proved promising in the assessment of disease severity and provides an easy-to-use platform for future investigation of Lassa pathogenesis and drug development in a human-like setting.
Topics: Human Umbilical Vein Endothelial Cells; Humans; Lab-On-A-Chip Devices; Lassa Fever; Lassa virus; Microfluidic Analytical Techniques; Models, Biological; Shock, Hemorrhagic; Syndrome
PubMed: 33241859
DOI: 10.1002/bit.27636 -
Emerging Infectious Diseases Feb 2016
Topics: Animals; Communicable Diseases; Cross Reactions; Humans; Immunoglobulin G; Immunoglobulin M; Insect Vectors; Mali; Seroepidemiologic Studies; Tick-Borne Diseases
PubMed: 26812625
DOI: 10.3201/eid2202.150688