Reverse Genetics Approaches to Control Arenavirus


Several arenavirus cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. To date, no licensed vaccines are available to combat human arenavirus infections, and anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetics approaches provides investigators with a novel and powerful approach for the investigation of the arenavirus molecular and cell biology. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription and the identification of novel anti-arenaviral drug targets without requiring the use of live forms of arenaviruses. Likewise, it is now feasible to rescue infectious arenaviruses entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify anti-arenaviral drugs and development of novel live-attenuated arenavirus vaccines. Recently, reverse genetics have also allowed the generation of tri-segmented arenaviruses expressing foreign genes, facilitating virus detection and opening the possibility of implementing live-attenuated arenavirus-based vaccine vector approaches. Likewise, the development of single-cycle infectious, reporter-expressing, arenaviruses has provided a new experimental method to s…

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In 2019, a small outbreak of Bolivian hemorrhagic fever was reported at a hospital in La Paz, Bolivia.  The following background data on Bolivian hemorrhagic fever are abstracted from Gideon www.GideonOnline.com and the Gideon e-book series. [1,2]  Primary references are available from the author.
Bolivian hemorrhagic fever (BHF) is caused by Machupo virus (Arenaviridae, Tacaribe complex, Mammarenavirus).  The disease was initially described in 1959 as a sporadic hemorrhagic illness in rural areas of Beni department, eastern Bolivia; and the virus itself was first identified in 1963.  BHF is most common…

Source: GIDEON blogCategory: Databases & Libraries Authors: Tags: Ebooks Epidemiology Outbreaks ProMED Source Type: blogs

Publication date: Available online 19 January 2019Source: Antiviral ResearchAuthor(s): Anne Leske, Irke Waßmann, Kevin Schnepel, Kyle Shifflett, Julia Holzerland, Linus Bostedt, Patrick Bohn, Thomas C. Mettenleiter, Ana M. Briggiler, Julia Brignone, Delia Enria, Sandra M. Cordo, Thomas Hoenen, Allison GrosethAbstractArenaviruses cause several viral hemorrhagic fevers endemic to Africa and South America. The respective causative agents are classified as biosafety level (BSL) 4 pathogens. Unlike for most other BSL4 agents, for the New World arenavirus Junín virus (JUNV) both a highly effective vaccination (Candi…

Assessing cross-reactivity of Junín virus-directed neutralizing antibodies.
Antiviral Res. 2019 Jan 19;:
Authors: Leske A, Waßmann I, Schnepel K, Shifflett K, Holzerland J, Bostedt L, Bohn P, Mettenleiter TC, Briggiler AM, Brignone J, Enria D, Cordo SM, Hoenen T, Groseth A
Abstract
Arenaviruses cause several viral hemorrhagic fevers endemic to Africa and South America. The respective causative agents are classified as biosafety level (BSL) 4 pathogens. Unlike for most other BSL4 agents, for the New World arenavirus Junín virus (JUNV) both a highly effective vaccination (Candid#1) a…

Source: Antiviral ResearchCategory: Virology Authors: Tags: Antiviral Res Source Type: research

by Almudena Mari Saez, Mory Cherif Haidara, Amara Camara, Fod é Kourouma, Mickaël Sage, N’Faly Magassouba, Elisabeth Fichet-Calvet

Lassa fever is a viral haemorrhagic fever caused by an arenavirus. The disease is endemic in West African countries, including Guinea. The rodentsMastomys natalensis andMastomys erythroleucus have been identified as Lassa virus reservoirs in Guinea. In the absence of a vaccine, rodent control and human behavioural changes are the only options to prevent Lassa fever in highly endemic areas. We performed a 4 year intervention based on chemical rodent control, utilizing anticoagulant …

Publication date: Available online 19 July 2018Source: Antiviral ResearchAuthor(s): Eric C. Dunham, Anne Leske, Kyle Shifflett, Ari Watt, Heinz Feldmann, Thomas Hoenen, Allison GrosethAbstractInfection with Junín virus (JUNV) is currently being effectively managed in the endemic region using a combination of targeted vaccination and plasma therapy. However, the long-term sustainability of plasma therapy is unclear and similar resources are not available for other New World arenaviruses. As a result, there has been renewed interest regarding the potential of drug-based therapies. To facilitate work on this issue, we …

Abstract
Infection with Junín virus (JUNV) is currently being effectively managed in the endemic region using a combination of targeted vaccination and plasma therapy. However, the long-term sustainability of plasma therapy is unclear and similar resources are not available for other New World arenaviruses. As a result, there has been renewed interest regarding the potential of drug-based therapies. To facilitate work on this issue, we present the establishment and subsequent optimization of a JUNV minigenome system to a degree suitable for high-throughput miniaturization, thereby providing a screening plat…

Source: Antiviral ResearchCategory: Virology Authors: Tags: Antiviral Res Source Type: research

Lassa virus is an Old World arenavirus endemic to West Africa that causes severe hemorrhagic fever. Vaccine development has focused on the envelope glycoprotein complex (GPC) that extends from the virion envelope. The often inadequate antibody immune response elicited by both vaccine and natural infection has been, in part, attributed…

Source: Proceedings of the National Academy of SciencesCategory: Science Authors: Tags: Biological Sciences Source Type: research

In this study, we investigated the spatial behavior ofM. natalensis and other small rodents in two capture-mark-recapture and four dyed bait (Rhodamine B) experiments in Lassa fever-endemic villages in Upper Guinea. During the capture-mark-recapture studies, 23% of the recapturedM. natalensis moved between the houses and proximate fields. WhileM. natalensis was found over the entire study grid (2  ha), other rodent species (Praomys daltoni, Praomys rostratus, Lemniscomys striatus, Mus spp.) were mostly trapped in the surrounding fields. Distances between recapture occasions never exceeded 100  m for all rodent sp…

Source: EcoHealthCategory: Environmental Health Source Type: research

Abstract
Arenavirus is a genetic term for viruses belonging to the family Arenaviridae and is presented from lymphocytic choriomeningitis virus (LCMV), which shows almost no pathogenicity to humans, to Lassa virus, Junin virus, Machupo virus, Chapare virus, Lujo virus, Sabia virus, and Guanarito virus, which shows high pathogenicity to humans. These viruses except for LCMV are risk group 4 pathogens specified by World Health Organization. Based on this designation, it is designated as Class I pathogens in Japan. Although there have been no reports excluding one imported case of the Lassa fever patient, it is not s…

Abstract
Lassa virus (LASV) is the most prevalent rodent-borne arenavirus circulated in West Africa. With population at risk from Senegal to Nigeria, LASV causes Lassa fever and is responsible for thousands of deaths annually. High genetic diversity of LASV is one of the challenges for vaccine R&D. We developed multivalent virus-like particle vectors (VLPVs) derived from the human Venezuelan equine encephalitis TC-83 IND vaccine (VEEV) as the next generation of alphavirus-based bicistronic RNA replicon particles. The genes encoding VEEV structural proteins were replaced with LASV glycoproteins (GPC) from distantly…

Source: VaccineCategory: Allergy & Immunology Authors: Tags: Vaccine Source Type: research



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