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Current Opinion in Virology Aug 2019Lassa fever is a unique viral hemorrhagic fever that is endemic in parts of West Africa, primarily Sierra Leone, Guinea, Liberia, and Nigeria. The disease is caused by... (Review)
Review
Lassa fever is a unique viral hemorrhagic fever that is endemic in parts of West Africa, primarily Sierra Leone, Guinea, Liberia, and Nigeria. The disease is caused by the Lassa virus, an Old World arenavirus that has as primary reservoir host the multimammate rodent Mastomys nataliensis, which lives in association with humans. Recent estimates suggest LF causes two million cases and 5000-10000 deaths annually, mainly in West Africa. Clinical diagnosis and laboratory confirmation have always been major challenges for effective management and control of the disease in afflicted areas of West Africa. Recent advancements in molecular biology, recombinant DNA technology, and genomics sequencing has facilitated major advancement in development of better diagnostic and surveillance tools for Lassa fever virus. These include, the multiplex, magnetic bead-based immunodiagnostics for both Lassa virus antigens and antibodies; molecular probe-based quantitative real-time PCR for genomic signatures; rapid diagnostics tests that detects the most prevalent West African lineages; and the successful utilization of next-generation sequencing technology to diagnose and characterize Lassa virus in West Africa. These advances will continue to improve disease treatment, control, and prevention. In this review we will discuss progression of Lassa virus diagnostics from the past and into the future.
Topics: Africa, Western; Antigens, Viral; Clinical Laboratory Techniques; Genomics; Humans; Lassa Fever; Lassa virus; Molecular Diagnostic Techniques; Serologic Tests
PubMed: 31518896
DOI: 10.1016/j.coviro.2019.08.002 -
Current Topics in Microbiology and... 2016The family Arenaviridae currently comprises over 20 viral species, each of them associated with a main rodent species as the natural reservoir and in one case possibly... (Review)
Review
The family Arenaviridae currently comprises over 20 viral species, each of them associated with a main rodent species as the natural reservoir and in one case possibly phyllostomid bats. Moreover, recent findings have documented a divergent group of arenaviruses in captive alethinophidian snakes. Human infections occur through mucosal exposure to aerosols or by direct contact of abraded skin with infectious materials. Arenaviruses merit interest both as highly tractable experimental model systems to study acute and persistent infections and as clinically important human pathogens including Lassa (LASV) and Junin (JUNV) viruses, the causative agents of Lassa and Argentine hemorrhagic fevers (AHFs), respectively, for which there are no FDA-licensed vaccines, and current therapy is limited to an off-label use of ribavirin (Rib) that has significant limitations. Arenaviruses are enveloped viruses with a bi-segmented negative strand (NS) RNA genome. Each genome segment, L (ca 7.3 kb) and S (ca 3.5 kb), uses an ambisense coding strategy to direct the synthesis of two polypeptides in opposite orientation, separated by a noncoding intergenic region (IGR). The S genomic RNA encodes the virus nucleoprotein (NP) and the precursor (GPC) of the virus surface glycoprotein that mediates virus receptor recognition and cell entry via endocytosis. The L genome RNA encodes the viral RNA-dependent RNA polymerase (RdRp, or L polymerase) and the small (ca 11 kDa) RING finger protein Z that has functions of a bona fide matrix protein including directing virus budding. Arenaviruses were thought to be relatively stable genetically with intra- and interspecies amino acid sequence identities of 90-95 % and 44-63 %, respectively. However, recent evidence has documented extensive arenavirus genetic variability in the field. Moreover, dramatic phenotypic differences have been documented among closely related LCMV isolates. These data provide strong evidence of viral quasispecies involvement in arenavirus adaptability and pathogenesis. Here, we will review several aspects of the molecular biology of arenaviruses, phylogeny and evolution, and quasispecies dynamics of arenavirus populations for a better understanding of arenavirus pathogenesis, as well as for the development of novel antiviral strategies to combat arenavirus infections.
Topics: Animals; Antiviral Agents; Arenaviridae Infections; Arenavirus; Evolution, Molecular; Genetic Variation; Genome, Viral; Humans; Phylogeny; Virus Replication
PubMed: 26472215
DOI: 10.1007/82_2015_468 -
Clinical Microbiology and Infection :... Apr 2019Viral haemorrhagic fever can be caused by one of a diverse group of viruses that come from four different families of RNA viruses. Disease severity can vary from mild... (Review)
Review
Viral haemorrhagic fever can be caused by one of a diverse group of viruses that come from four different families of RNA viruses. Disease severity can vary from mild self-limiting febrile illness to severe disease characterized by high fever, high-level viraemia, increased vascular permeability that can progress to shock, multi-organ failure and death. Despite the urgent need, effective treatments and preventative vaccines are currently lacking for the majority of these viruses. A number of factors preclude the effective study of these diseases in humans including the high virulence of the agents involved, the sporadic nature of outbreaks of these viruses, which are typically in geographically isolated areas with underserviced diagnostic capabilities, and the requirements for high level bio-containment. As a result, animal models that accurately mimic human disease are essential for advancing our understanding of the pathogenesis of viral haemorrhagic fevers. Moreover, animal models for viral haemorrhagic fevers are necessary to test vaccines and therapeutic intervention strategies. Here, we present an overview of the animal models that have been established for each of the haemorrhagic fever viruses and identify which aspects of human disease are modelled. Furthermore, we discuss how experimental design considerations, such as choice of species and virus strain as well as route and dose of inoculation, have an influence on animal model development. We also bring attention to some of the pitfalls that need to be avoided when extrapolating results from animal models.
Topics: Animals; Arenaviridae; Bunyaviridae; Disease Models, Animal; Filoviridae; Flaviviridae; Hemorrhagic Fevers, Viral; Humans
PubMed: 24690109
DOI: 10.1111/1469-0691.12630 -
Methods in Molecular Biology (Clifton,... 2022Reverse genetics systems provide a powerful tool to generate recombinant arenavirus expressing reporters to facilitate the investigation of the arenavirus life cycle and...
Reverse genetics systems provide a powerful tool to generate recombinant arenavirus expressing reporters to facilitate the investigation of the arenavirus life cycle and also for the discovery of antiviral countermeasures. The plasmid-encoded viral ribonucleoprotein components initiate the transcription and replication of a plasmid-driven full-length viral genome, resulting in infectious virus. Thereby, this approach is ideal for the generation of recombinant arenaviruses expressing reporter genes that can be used as valid surrogates for virus replication. By splitting the small viral segment (S) into two viral segments (S1 and S2), each of them encoding a reporter gene, recombinant tri-segmented arenavirus can be rescued. Bi-reporter-expressing recombinant tri-segmented arenaviruses represent an excellent tool to study the biology of arenaviruses, including the identification and characterization of both prophylactic and therapeutic countermeasures for the treatment of arenaviral infections. In this chapter, we describe a detailed protocol on the generation and in vitro characterization of recombinant arenaviruses containing a tri-segment genome expressing two reporter genes based on the prototype member in the family, lymphocytic choriomeningitis virus (LCMV). Similar experimental approaches can be used for the generation of bi-reporter-expressing tri-segment recombinant viruses for other members in the arenavirus family.
Topics: Arenaviridae Infections; Genes, Reporter; Humans; Lymphocytic choriomeningitis virus; Reverse Genetics; Virus Replication
PubMed: 35821475
DOI: 10.1007/978-1-0716-2453-1_17 -
Expert Review of Vaccines 2024
Topics: Humans; Vaccines; Virus Replication; Lassa virus; Lassa Fever; Arenaviridae Infections
PubMed: 38044877
DOI: 10.1080/14760584.2023.2290683 -
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 -
Travel Medicine and Infectious Disease 2022Only two naturally occurring human Sabiá virus (SABV) infections have been reported, and those occurred over 20 years ago.
BACKGROUND
Only two naturally occurring human Sabiá virus (SABV) infections have been reported, and those occurred over 20 years ago.
METHODS
We diagnosed two new cases of SABV infection using metagenomics in patients thought to have severe yellow fever and described new features of histopathological findings.
RESULTS
We characterized clinical manifestations, histopathology and analyzed possible nosocomial transmission. Patients presented with hepatitis, bleeding, neurological alterations and died. We traced twenty-nine hospital contacts and evaluated them clinically and by RT-PCR and neutralizing antibodies. Autopsies uncovered unique features on electron microscopy, such as hepatocyte "pinewood knot" lesions. Although previous reports with similar New-World arenavirus had nosocomial transmission, our data did not find any case in contact tracing.
CONCLUSIONS
Although an apparent by rare, Brazilian mammarenavirus infection is an etiology for acute hemorrhagic fever syndrome. The two fatal cases had peculiar histopathological findings not previously described. The virological diagnosis was possible only by contemporary techniques such as metagenomic assays. We found no subsequent infections when we used serological and molecular tests to evaluate close contacts.
Topics: Antibodies, Neutralizing; Arenaviruses, New World; Brazil; Cross Infection; Humans; Yellow Fever
PubMed: 35537676
DOI: 10.1016/j.tmaid.2022.102351 -
Current Opinion in Virology Jun 2016Surface glycoproteins direct cellular targeting, attachment, and membrane fusion of arenaviruses and are the primary target for neutralizing antibodies. Despite... (Review)
Review
Surface glycoproteins direct cellular targeting, attachment, and membrane fusion of arenaviruses and are the primary target for neutralizing antibodies. Despite significant conservation of the glycoprotein architecture across the arenavirus family, there is considerable variation in the molecular recognition mechanisms used during host cell entry. We review recent progress in dissecting these infection events and describe how arenaviral glycoproteins can be targeted by small-molecule antivirals, the natural immune response, and immunoglobulin-based therapeutics. Arenaviral glycoprotein-mediated assembly and infection pathways present numerous opportunities and challenges for therapeutic intervention.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Antiviral Agents; Arenaviridae Infections; Arenavirus; Humans; Membrane Fusion; Membrane Glycoproteins; Mice; Viral Envelope Proteins; Viral Vaccines; Virus Internalization
PubMed: 27104809
DOI: 10.1016/j.coviro.2016.04.001 -
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 -
Current Opinion in Virology Aug 2019Lassa fever is a zoonotic disease caused by the Lassa virus, a rodent-borne arenavirus endemic to West Africa. Recent steady increase in reported cases of the disease in... (Review)
Review
Lassa fever is a zoonotic disease caused by the Lassa virus, a rodent-borne arenavirus endemic to West Africa. Recent steady increase in reported cases of the disease in Nigeria, where 123 deaths occurred in 546 confirmed cases in 2019 has further underlined the need to accelerate the development of vaccines for preventing the disease. Intensified research and development of Lassa fever medical countermeasures have yielded some vaccine candidates with preclinical scientific plausibility using predominantly novel technology. The more advanced candidates are based on recombinant measles, Vesicular Stomatitis Virus or Mopiea and Lassa virus reassortants expressing Lassa virus antigens, and the deoxyribonucleic acid platform. However, the Lassa fever portfolio still lags behind other neglected tropical diseases', and further investments are needed for continued development and additional research, such as the safety and efficacy of these vaccine candidates in special populations.
Topics: Animals; Antigens, Viral; Clinical Trials as Topic; Disease Models, Animal; Humans; Lassa Fever; Lassa virus; Rodentia; Viral Vaccines
PubMed: 31472333
DOI: 10.1016/j.coviro.2019.07.006