-
Current Opinion in Virology Aug 2019
Topics: Africa; Animals; Disease Models, Animal; Humans; Lassa Fever; Lassa virus; Sequence Analysis, DNA
PubMed: 31564289
DOI: 10.1016/j.coviro.2019.09.001 -
Critical Reviews in Clinical Laboratory... 2004Lassa virus is a RNA virus belonging to the family of Arenaviridae. It was discovered as the causative agent of a hemorrhagic fever--Lassa fever--about 30 years ago.... (Review)
Review
Lassa virus is a RNA virus belonging to the family of Arenaviridae. It was discovered as the causative agent of a hemorrhagic fever--Lassa fever--about 30 years ago. Lassa fever is endemic in West Africa and is estimated to affect some 100,000 people annually. Great progress in the understanding of the life cycle of arenaviruses, including Lassa virus, has been made in recent years. New insights have been gained in the pathogenesis and molecular epidemiology of Lassa fever, and state-of the-art technologies for diagnosing this life-threatening disease have been developed. The intention of this review is to summarize in particular the recent literature on Lassa virus and Lassa fever. Several aspects ranging from basic research up to clinical practice and laboratory diagnosis are discussed and linked together.
Topics: Gene Expression Regulation, Viral; Genetic Variation; Glycoproteins; Humans; Lassa Fever; Lassa virus; Phylogeny; Viral Proteins; Viral Vaccines
PubMed: 15487592
DOI: 10.1080/10408360490497456 -
Current Topics in Microbiology and... 2023Lassa Fever (LF) is a viral hemorrhagic fever endemic in West Africa. LF begins with flu-like symptoms that are difficult to distinguish from other common endemic...
Lassa Fever (LF) is a viral hemorrhagic fever endemic in West Africa. LF begins with flu-like symptoms that are difficult to distinguish from other common endemic diseases such as malaria, dengue, and yellow fever making it hard to diagnose clinically. Availability of a rapid diagnostic test and other serological and molecular assays facilitates accurate diagnosis of LF. Lassa virus therapeutics are currently in different stages of preclinical development. Arevirumab, a cocktail of monoclonal antibodies, demonstrates a great safety and efficacy profile in non-human primates. Major efforts have been made in the development of a Lassa virus vaccine. Two vaccine candidates, MeV-NP and pLASV-GPC are undergoing evaluation in phase I clinical trials.
Topics: Animals; Lassa virus; Viral Vaccines; Lassa Fever; Primates; Africa, Western
PubMed: 36253593
DOI: 10.1007/82_2022_261 -
Current Topics in Microbiology and... 2023In a pattern repeated across a range of ecological niches, arenaviruses have evolved a compact four-gene genome to orchestrate a complex life cycle in a narrow range of...
In a pattern repeated across a range of ecological niches, arenaviruses have evolved a compact four-gene genome to orchestrate a complex life cycle in a narrow range of susceptible hosts. A number of mammalian arenaviruses cross-infect humans, often causing a life-threatening viral hemorrhagic fever. Among this group of geographically bound zoonoses, Lassa virus has evolved a unique niche that leads to significant and sustained human morbidity and mortality. As a biosafety level 4 pathogen, direct study of the pathogenesis of Lassa virus is limited by the sparse availability, high operating costs, and technical restrictions of the high-level biocontainment laboratories required for safe experimentation. In this chapter, we introduce the relationship between genome structure and the life cycle of Lassa virus and outline reverse genetic approaches used to probe and describe functional elements of the Lassa virus genome. We then review the tools used to obtain viral genomic sequences used for phylogeny and molecular diagnostics, before shifting to a population perspective to assess the contributions of phylogenetic analysis in understanding the evolution and ecology of Lassa virus in West Africa. We finally consider the future outlook and clinical applications for genetic study of Lassa virus.
Topics: Animals; Humans; Lassa virus; Lassa Fever; Phylogeny; Africa, Western; Zoonoses; Mammals
PubMed: 32418034
DOI: 10.1007/82_2020_212 -
F1000Research 2019Lassa virus (LASV) is a highly prevalent mammarenavirus in West Africa and is maintained in nature in a persistently infected rodent host, , which is widely spread in... (Review)
Review
Lassa virus (LASV) is a highly prevalent mammarenavirus in West Africa and is maintained in nature in a persistently infected rodent host, , which is widely spread in sub-Saharan Africa. LASV infection of humans can cause Lassa fever (LF), a disease associated with high morbidity and significant mortality. Recent evidence indicates an LASV expansion outside its traditional endemic areas. In 2017, the World Health Organization (WHO) included LASV in top-priority pathogens and released a Target Product Profile (TPP) for vaccine development. Likewise, in 2018, the US Food and Drug Administration added LF to a priority review voucher program to encourage the development of preventive and therapeutics measures. In this article, we review recent progress in LASV vaccine research and development with a focus on the impact of LASV genetic and biological diversity on the design and development of vaccine candidates meeting the WHO's TPP for an LASV vaccine.
Topics: Africa, Western; Animals; Humans; Lassa Fever; Lassa virus; Murinae; Viral Vaccines
PubMed: 30774934
DOI: 10.12688/f1000research.16989.1 -
Bioscience Reports Feb 2022Lassa virus (LASV), an arenavirus endemic to West Africa, causes Lassa fever-a lethal hemorrhagic fever. Entry of LASV into the host cell is mediated by the glycoprotein... (Review)
Review
Lassa virus (LASV), an arenavirus endemic to West Africa, causes Lassa fever-a lethal hemorrhagic fever. Entry of LASV into the host cell is mediated by the glycoprotein complex (GPC), which is the only protein located on the viral surface and comprises three subunits: glycoprotein 1 (GP1), glycoprotein 2 (GP2), and a stable signal peptide (SSP). The LASV GPC is a class one viral fusion protein, akin to those found in viruses such as human immunodeficiency virus (HIV), influenza, Ebola virus (EBOV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These viruses are enveloped and utilize membrane fusion to deliver their genetic material to the host cell. Like other class one fusion proteins, LASV-mediated membrane fusion occurs through an orchestrated sequence of conformational changes in its GPC. The receptor-binding subunit, GP1, first engages with a host cell receptor then undergoes a unique receptor switch upon delivery to the late endosome. The acidic pH and change in receptor result in the dissociation of GP1, exposing the fusion subunit, GP2, such that fusion can occur. These events ultimately lead to the formation of a fusion pore so that the LASV genetic material is released into the host cell. Interestingly, the mature GPC retains its SSP as a third subunit-a feature that is unique to arenaviruses. Additionally, the fusion domain contains two separate fusion peptides, instead of a standard singular fusion peptide. Here, we give a comprehensive review of the LASV GPC components and their unusual features.
Topics: Glycoproteins; Humans; Lassa virus; Viral Envelope Proteins; Virus Internalization
PubMed: 35088070
DOI: 10.1042/BSR20211930 -
Current Opinion in Virology Aug 2019In humans, Lassa virus infection can result in disease with hemorrhagic manifestations and high fatality rates. There are no approved treatments or vaccines available... (Review)
Review
In humans, Lassa virus infection can result in disease with hemorrhagic manifestations and high fatality rates. There are no approved treatments or vaccines available and the inherent danger of studying Lassa virus means it can only be studied in high containment labs (BSL4). Under these conditions, mouse models are becoming an important instrument in the study of Lassa virus infection, disease and host responses. While guinea pigs and non-human primates are the critical components in assessing treatments and vaccines and have recently been used with great affect in this capacity.
Topics: Animals; Disease Models, Animal; Guinea Pigs; Humans; Lassa Fever; Lassa virus; Mice; Murinae; Primates; Viral Vaccines
PubMed: 31442921
DOI: 10.1016/j.coviro.2019.07.005 -
Current Opinion in Virology Aug 2018The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding... (Review)
Review
The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding and fusion subunits. Recent engineering efforts to stabilize the glycoprotein of the Old World arenavirus Lassa in a native, yet cleaved state, allowed the first structure of any arenavirus prefusion GPC trimer to be determined. Comparison of this structure with the structures of other arenavirus glycoprotein subunits reveals surprising findings: that the receptor binding subunit, GP1, of Lassa virus is conformationally labile, while the GP1 subunit of New World arenaviruses is not, and that the arenavirus GPC adopts a trimeric state unlike other glycoproteins with similar fusion machinery. Structural analysis, combined with recent biochemical data regarding antibody epitopes and receptor binding requirements, provides a basis for rational vaccine design.
Topics: Arenavirus; Epitopes; Glycoproteins; Humans; Lassa virus; Protein Binding; Protein Structure, Tertiary; Viral Envelope Proteins; Virus Internalization
PubMed: 29843991
DOI: 10.1016/j.coviro.2018.05.002 -
Current Topics in Microbiology and... 2023Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic fever that is endemic in West Africa. LASV virions are enveloped and contain two...
Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic fever that is endemic in West Africa. LASV virions are enveloped and contain two single-stranded RNA genome segments. Both segments are ambisense and encode two proteins. The nucleoprotein associates with viral RNAs forming ribonucleoprotein complexes. The glycoprotein complex mediates viral attachment and entry. The Zinc protein serves as the matrix protein. Large is a polymerase that catalyzes viral RNA transcription and replication. LASV virion entry occurs via a clathrin-independent endocytic pathway usually involving alpha-dystroglycan and lysosomal associated membrane protein 1 as surface and intracellular receptors, respectively. Advances in understanding LASV structural biology and replication have facilitated development of promising vaccine and drug candidates.
Topics: Humans; Lassa virus; Lassa Fever; Biology; Africa, Western
PubMed: 37100973
DOI: 10.1007/82_2023_262 -
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