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Decoding arenavirus pathogenesis: essential roles for alpha-dystroglycan-virus interactions and the immune response.

Pathogenesis following a virus infection results from interactions between the virus and its host. The outcome is determined by tipping the balance between virulence of the virus or susceptibility/resistance of the host to favor one or the other. This review focuses on two important members of the Old World arenavirus family: Lassa fever virus (LFV), a robust human pathogen that causes a severe acute hemorrhagic disease; and lymphocytic choriomeningitis virus (LCMV), also a human pathogen but better known in the context of its rodent model. Research with this model has uncovered and illuminate

Rabies human diploid cell vaccine elicits cross-neutralising and cross-protecting immune responses against European and Australian bat lyssaviruses.

The ability of antibodies elicited against the rabies human diploid cell vaccine (HDCV) to neutralise European bat Lyssaviruses (EBLV types-1 and -2), Australian bat Lyssavirus and classical rabies virus (RABV) has been evaluated using modified fluorescent antibody virus neutralisation (mFAVN) assays. Ninety-six percent (48 of 50) of the human post-vaccinated sera tested cross-neutralised these viruses (>or=0.5 IU/ml). Cross-protection experiments using inbred mice (RIII, k/k haplotype) were also assessed. Mice were given HDCV (twice by the intra-peritoneal route) and challenged (intra-cranial

Differential Immune Responses to Hemorrhagic Fever-Causing Arenaviruses.

The family Arenaviridae contains several pathogens of major clinical importance. The Old World (OW) arenavirus Lassa virus is endemic in West Africa and is estimated to cause up to 300,000 infections each year. The New World (NW) arenaviruses Junín and Machupo periodically cause hemorrhagic fever outbreaks in South America. While these arenaviruses are highly pathogenic in humans, recent evidence indicates that pathogenic OW and NW arenaviruses interact with the host immune system differently, which may have differential impacts on viral pathogenesis. Severe Lassa fever cases are characterized…

[South American Hemorrhagic Fever viruses and the cutting edge of the vaccine and antiviral development].

South American Hemorrhagic Fever is caused by the Arenavirus, which belong to the Family Arenaviridae, genus mammarenavirus, infection at South America. South American Hemorrhagic Fever includes 1. Argentinian Hemorrhagic fever caused by Junin virus, 2. Brazilian hemorrhagic fever caused by Sabia virus, 3. Venezuelan Hemorrhagic fever caused by Guanarito virus, 4. Bolivian Hemorrhagic fever caused by Machupo virus, and 5. Unassigned hemorrhagic fever caused by Chapare virus. These viruses are classified in New World (NW) Arenavirus, which is different from Old World Arenavirus (ex. Lassa virus…

A fractional-order analysis of recurrent Lassa fever transmission in Nigeria.

The recurrence of Lassa fever in Nigeria is sustained by human, hospital, rodent, and environmental routes. However, many existing models do not simultaneously capture asymptomatic infection, nosocomial spread, imperfect isolation, and epidemiological memory. This study develops a Caputo fractional-order model that integrates these mechanisms within a single system. The model is shown to admit a unique, non-negative, bounded solution in a positively invariant feasible region. The human-environment reproduction threshold is derived using the next-generation matrix method, while the rodent subsy

Alteration of ssRNA Torsion and Water Influx into ssRNA Pocket in K309A and S247A Mutations.

BACKGROUND: Lassa Virus (LV) infection is an endemic disease from West Africa posing threat to the entire world. A thorough understanding of the mechanistic workings of the genome products of LV may be a key to develop drug candidates for the treatment of LV infection. METHODS: Molecular dynamic simulation has been used to provide insight into the mechanistic basis for total loss of ssRNA interaction in Nucleoprotein (NP) K309A, partial loss in S247A, and no loss in S237A by following the hydrogen bond interaction, water influx into the ssRNA pocket and glycosidic torsion angle (χ) of the ssR…

Hunting and consumption of rodents by children in the Lassa fever endemic area of Faranah, Guinea.

As a consequence of the Ebola outbreak, human-animal contact has gained importance for zoonotic transmission surveillance. In Faranah (Upper Guinea), daily life is intertwined with rodents, such as the Natal multimammate mouse, Mastomys natalensis; a reservoir for Lassa virus (LASV). However, this contact is rarely perceived as a health risk by residents, although Lassa fever (LF) is known to be endemic to this region. Conversely, these observations remain a great concern for global health agendas. Drawing on ethnographic research involving interviews, focus group discussions, participant obse…

Metagenomic sequencing at the epicenter of the Nigeria 2018 Lassa fever outbreak.

The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health

When Viruses Don't Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses.

Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographi … ic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.

Сканирование по всему геному дает основания для положительного отбора генов, связанных с лихорадкой Ласса.

Быстро развивающиеся вирусы и другие патогены могут оказывать огромное воздействие на эволюцию человека, поскольку естественный отбор приводит к увеличению распространенности генетических вариантов, обеспечивающих устойчивость к болезням. С появлением больших наборов данных о генетической вариации человека мы можем искать подписи естественного отбора в геноме человека под воздействием таких микроорганизмов, вызывающих болезни. Исходя из этого подхода, мы ранее гипотезуем, что вирус Ласса (LASV), возможно, был движущей силой естественного отбора населения Западной Африки, где геморрагическая ли

Совпадение в аннотации оригинала
Rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevale … y such disease-causing microorganisms. Based on this approach, we have previously hypothesized that Lassa virus (LASV) may have been a driver of natural selection in West African populations where Lassa haemorrhagic fever is endemic. In this study, we provide further evidence for this notion. By applying tests for selection to genome-wide data from the Intern …

Genomic and phylogenetic characterization of Merino Walk virus, a novel arenavirus isolated in South Africa.

Merino Walk virus (MWV), a proposed novel tentative species of the family Arenaviridae, was isolated from a rodent, Myotomys unisulcatus, collected at Merino Walk, Eastern Cape, South Africa, in 1985. Full-length genomic sequence confirmed MWV as an arenavirus related distantly to Mobala, Mopeia and Ippy viruses, all members of the Old World arenavirus complex. We propose MWV as a tentative novel species in the Lassa-lymphocytic choriomeningitis virus complex, based on its isolation from a novel rodent species and its genetic and serological characteristics.

Arenavirus taxonomy: a review.

Despite a late beginning, the construction of the arenavirus taxon and its placement in the scheme of the International Committee on Taxonomy of Viruses has now been completed. The bringing together of the member viruses has already provided valuable indications of promising laboratory and field study approaches; in the future this classification will contribute further to our understanding of the natural history and disease processes of the human pathogens of the group.

Flunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses.

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vR…

Variations in Core Packing of GP2 from Old World Mammarenaviruses in their Post-Fusion Conformations Affect Membrane-Fusion Efficiencies.

Lassa virus (LASV) is a notorious human pathogen in West Africa. Its class I trimeric spike complex displays a distinct architecture, and its cell entry mechanism involves unique attributes not shared by other related viruses. We determined the crystal structure of the GP2 fusion glycoprotein from the spike complex of LASV (GP2LASV) in its post-fusion conformation. GP2LASV adopts a canonical helical bundle configuration similarly to other viruses in its family. The core packing of GP2LASV, however, is more organized compared to GP2 from other viruses reducing the formation of internal hydropho…

The use of mice lacking type I or both type I and type II interferon responses in research on hemorrhagic fever viruses. Part 2: Vaccine efficacy studies.

For more than 20 years, researchers have used laboratory mice lacking type I or both type I and II interferon (IFN) responses to study high-containment viruses that cause hemorrhagic fevers (HF) in humans. With the exception of Rift Valley fever virus, agents that cause viral HF in humans, such as Ebola and Lassa virus, do not cause disease in mature immunocompetent mice. In contrast, IFN-deficient mice typically develop severe or fatal disease when inoculated with these agents. The sensitivity of IFN-deficient mice to disease has led to their widespread use in biocontainment laboratories to a…