scholarly journals Lassa Fever Virus Binds Matriglycan—A Polymer of Alternating Xylose and Glucuronate—On α-Dystroglycan

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1679
Author(s):  
Soumya Joseph ◽  
Kevin P. Campbell
Keyword(s):  
Viral Entry ◽  
Tyrosine Kinases ◽  
Lassa Fever ◽  
Fever Virus ◽  
Phagocytic Cells ◽  
Hemorrhagic Fevers ◽  
Lassa Fever Virus ◽  
Clade C ◽  
Additional Cell ◽  
Life Threatening

Lassa fever virus (LASV) can cause life-threatening hemorrhagic fevers for which there are currently no vaccines or targeted treatments. The late Prof. Stefan Kunz, along with others, showed that the high-affinity host receptor for LASV, and other Old World and clade-C New World mammarenaviruses, is matriglycan—a linear repeating disaccharide of alternating xylose and glucuronic acid that is polymerized uniquely on α-dystroglycan by like-acetylglucosaminyltransferase-1 (LARGE1). Although α-dystroglycan is ubiquitously expressed, LASV preferentially infects vascular endothelia and professional phagocytic cells, which suggests that viral entry requires additional cell-specific factors. In this review, we highlight the work of Stefan Kunz detailing the molecular mechanism of LASV binding and discuss the requirements of receptors, such as tyrosine kinases, for internalization through apoptotic mimicry.

scholarly journals pH-Induced Activation of Arenavirus Membrane Fusion Is Antagonized by Small-Molecule Inhibitors

2008 ◽  
Vol 82 (21) ◽  
pp. 10932-10939 ◽  
Author(s):  
Joanne York ◽  
Dongcheng Dai ◽  
Sean M. Amberg ◽  
Jack H. Nunberg
Keyword(s):  
Membrane Fusion ◽  
Small Molecule ◽  
Viral Entry ◽  
De Novo ◽  
Lassa Fever ◽  
Molecular Target ◽  
Active Inhibitor ◽  
Hemorrhagic Fevers ◽  
Lassa Fever Virus ◽  
Small Molecule Compound

ABSTRACT The arenavirus envelope glycoprotein (GPC) mediates viral entry through pH-induced membrane fusion in the endosome. This crucial process in the viral life cycle can be specifically inhibited in the New World arenaviruses by the small-molecule compound ST-294. Here, we show that ST-294 interferes with GPC-mediated membrane fusion by targeting the interaction of the G2 fusion subunit with the stable signal peptide (SSP). We demonstrate that amino acid substitutions at lysine-33 of the Junín virus SSP confer resistance to ST-294 and engender de novo sensitivity to ST-161, a chemically distinct inhibitor of the Old World Lassa fever virus. These compounds, as well as a broadly active inhibitor, ST-193, likely share a molecular target at the SSP-G2 interface. We also show that both ST-294 and ST-193 inhibit pH-induced dissociation of the G1 receptor-binding subunit from GPC, a process concomitant with fusion activation. Interestingly, the inhibitory activity of these molecules can in some cases be overcome by further lowering the pH used for activation. Our results suggest that these small molecules act to stabilize the prefusion GPC complex against acidic pH. The pH-sensitive interaction between SSP and G2 in GPC represents a robust molecular target for the development of antiviral compounds for the treatment of arenavirus hemorrhagic fevers.

Molecular Detection and Characterisation of Lassa Fever Virus among Patients Attending Tertiary Hospitals in Jos, Central Nigeria

2018 ◽  
Vol 28 (4) ◽  
pp. 1-8
Author(s):  
Solomon Chuwang Chollom ◽  
Daniel Zanyu Egah ◽  
Patricial Lar ◽  
Sophia Osawe ◽  
Alash’le Abimiku
Keyword(s):  
Molecular Detection ◽  
Lassa Fever ◽  
Fever Virus ◽  
Lassa Fever Virus ◽  
Tertiary Hospitals

scholarly journals Old World and Clade C New World Arenaviruses Mimic the Molecular Mechanism of Receptor Recognition Used by α-Dystroglycan's Host-Derived Ligands

2007 ◽  
Vol 81 (11) ◽  
pp. 5685-5695 ◽  
Author(s):  
Jillian M. Rojek ◽  
Christina F. Spiropoulou ◽  
Kevin P. Campbell ◽  
Stefan Kunz
Keyword(s):  
New World ◽  
Critical Role ◽  
Lassa Fever ◽  
Lymphocytic Choriomeningitis ◽  
Old World ◽  
Ecm Proteins ◽  
Receptor Recognition ◽  
Lassa Fever Virus ◽  
Clade C

ABSTRACT α-Dystroglycan (DG) is an important cellular receptor for extracellular matrix (ECM) proteins and also serves as the receptor for Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) and clade C New World arenaviruses. In the host cell, α-DG is subject to a remarkably complex pattern of O glycosylation that is crucial for its interactions with ECM proteins. Two of these unusual sugar modifications, protein O mannosylation and glycan modifications involving the putative glycosyltransferase LARGE, have recently been implicated in arenavirus binding. Considering the complexity of α-DG O glycosylation, our present study was aimed at the identification of the specific O-linked glycans on α-DG that are recognized by arenaviruses. As previously shown for LCMV, we found that protein O mannosylation of α-DG is crucial for the binding of arenaviruses of distinct phylogenetic origins, including LFV, Mobala virus, and clade C New World arenaviruses. In contrast to the highly conserved requirement for O mannosylation, more generic O glycans present on α-DG are dispensable for arenavirus binding. Despite the critical role of O-mannosyl glycans for arenavirus binding under normal conditions, the overexpression of LARGE in cells deficient in O mannosylation resulted in highly glycosylated α-DG that was functional as a receptor for arenaviruses. Thus, modifications by LARGE but not O-mannosyl glycans themselves are most likely the crucial structures recognized by arenaviruses. Together, the data demonstrate that arenaviruses recognize the same highly conserved O-glycan structures on α-DG involved in ECM protein binding, indicating a strikingly similar mechanism of receptor recognition by pathogen- and host-derived ligands.

Lassa Fever Virus in Senegal

1988 ◽  
Vol 157 (3) ◽  
pp. 605-605 ◽  
Author(s):  
J. F. Saluzzo ◽  
F. Adam ◽  
J. B. McCormick ◽  
J. P. Digoutte
Keyword(s):  
Lassa Fever ◽  
Fever Virus ◽  
Lassa Fever Virus

scholarly journals Outbreak of Measles in vaccinated population in Southeastern Nigeria

2021 ◽  
Vol 22 (3) ◽  
pp. 336-343
Author(s):  
J.A. Shenge ◽  
G.N. Odaibo ◽  
D.O. Olaleye
Keyword(s):  
Rural Communities ◽  
Cell Lines ◽  
Measles Virus ◽  
Venous Blood ◽  
Febrile Illness ◽  
Lassa Fever ◽  
Fever Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Southeastern Nigeria ◽  
Lassa Fever Virus

Background: Outbreaks of respiratory disease, febrile illness and rash occurred in two adjoining rural communities of Imo State, Southeastern, Nigeria, at different times between 2006 and 2020. Laboratory investigation was carried out to determine the aetiological agent of the outbreak. Methodology: Oropharyngeal swabs were collected from 6 individuals showing symptoms of disease, within 3-4 days of appearance of rash. Venous blood samples were also collected from a total of 41 symptomatic persons, their contacts and individuals with resolved infections. Swabs were inoculated into Vero, HEp-2c, B95a and MDCK cell lines. Sera were analyzed using enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G and M to rubella and measles viruses, while immunofluorescence assay was used to detect Lassa fever virus immunoglobulins. Descriptive data were analyzed using the Statistical Package for the Social Sciences (SPSS). Results: Four of the 6 (66.7%) swab samples showed viral activity or cytopathic effect characterized by clumping of cells in Vero cells while 2 (33.3%) in Hep-2c characterized by rounding up of cells. Thirty-nine (95.1%) sera were positive for measles IgG while 13 (31.7%) were positive for IgM. Thirty-six (87.8%) sera were positive for rubella IgG but none was positive for IgM. None of the sera was positive for Lassa fever virus IgG and IgM. Conclusion: Measles virus was responsible for the outbreak among previously vaccinated population in the communities, while Rubella and Lassa fever viruses were excluded as the etiological agents of the outbreak. Keywords: Epidemics; IgG and IgM; Cell lines; Vaccination; Measles virus   French title: Épidémie de rougeole dans la population vaccinée du sud-est du Nigéria Contexte: Des flambées de maladies respiratoires, de maladies fébriles et d'éruptions cutanées sont survenues dans deux communautés rurales voisines de l'État d'Imo, dans le sud-est du Nigéria, à des moments différents entre 2006 et 2020. Une enquête en laboratoire a été menée pour déterminer l'agent étiologique de l'épidémie. Méthodologie: Des écouvillons oropharyngés ont été prélevés sur 6 individus présentant des symptômes de maladie, dans les 3 à 4 jours suivant l'apparition de l'éruption cutanée. Des échantillons de sang veineux ont également été prélevés sur un total de 41 personnes symptomatiques, leurs contacts et des personnes souffrant d'infections résolues. Des écouvillons ont été inoculés dans des lignées cellulaires Vero, HEp-2c, B95a et MDCK. Les sérums ont été analysés en utilisant un test immuno-enzymatique (ELISA) pour les immunoglobulines G et M contre les virus de la rubéole et de la rougeole, tandis que le test d'immunofluorescence a été utilisé pour détecter les immunoglobulines du virus de la fièvre de Lassa. Les données descriptives ont été analysées à l'aide du progiciel statistique pour les sciences sociales (SPSS). Résultats: Quatre des 6 échantillons sur écouvillon (66,7%) ont montré une activité virale ou un effet cytopathique caractérisé par l'agglutination des cellules dans les cellules Vero, tandis que 2 (33,3%) dans Hep-2c étaient caractérisés par un arrondissement des cellules. Trente-neuf (95,1%) sérums étaient positifs pour les IgG contre la rougeole tandis que 13 (31,7%) étaient positifs pour les IgM. Trente-six (87,8%) sérums étaient positifs pour les IgG contre la rubéole, mais aucun n'était positif pour les IgM. Aucun des sérums n'était positif pour les IgG et IgM du virus de la fièvre de Lassa. Conclusion: Le virus de la rougeole était responsable de l'épidémie parmi la population précédemment vaccinée dans les communautés, tandis que les virus de la rubéole et de la fièvre de Lassa ont été exclus comme agents étiologiques de l'épidémie. Mots clés: épidémies; IgG et IgM; Lignées cellulaires; Vaccination; Virus de la rougeole

scholarly journals Boosting understanding of Lassa Fever virus epidemiology: Field testing a novel assay to identify past Lassa Fever virus infection in blood and oral fluids of survivors and unexposed controls in Sierra Leone

2021 ◽  
Vol 15 (3) ◽  
pp. e0009255
Author(s):  
Onome Akpogheneta ◽  
Steve Dicks ◽  
Donald Grant ◽  
Zainab Kanneh ◽  
Brima Jusu ◽  
...  
Keyword(s):  
Sierra Leone ◽  
Sensitivity And Specificity ◽  
Large Scale ◽  
Oral Fluid ◽  
Field Testing ◽  
Lassa Fever ◽  
Fever Virus ◽  
World Health ◽  
Hospitalised Patients ◽  
Lassa Fever Virus

Background Despite identification 50 years ago, the true burden of Lassa Fever (LF) across Africa remains undefined for reasons including research focus on hospitalised patients, lack of validated field-feasible tools which reliably identify past infection, and the fact that all assays require blood samples making large-scale surveys difficult. Designated a priority pathogen of epidemic potential requiring urgent research by the World Health Organisation, a better understanding of LF sero-epidemiology is essential to developing and evaluating new interventions including vaccines. We describe the first field testing of a novel species-neutral Double Antigen Binding Assay (DABA) designed to detect antibodies to LF in plasma and oral fluid. Methodology/Principal findings Paired plasma and oral fluid were collected in Sierra Leone from survivors discharged from Kenema Government Hospital Lassa Fever Unit between 1980 and 2018, and from controls recruited in Freetown in 2019. Epidemiological sensitivity and specificity of the DABA measured against historical diagnosis in survivors and self-declared non-exposed controls was 81.7% (95% CI 70.7%– 89.9%) and 83.3% (72.7%- 91.1%) respectively in plasma, and 71.8% (60.0%– 81.9%) and 83.3% (72.7%– 91.1%) respectively in oral fluid. Antibodies were identified in people infected up to 15 years and, in one case, 40 years previously. Participants found oral fluid collection easy and painless with 80% happy to give an oral fluid sample regularly. Conclusions/Significance Given the difficulties of assay validation in a resource-limited setting, including unexpected exposures and diagnostics of varying accuracy, the new assay performed well in both plasma and oral fluid. Sensitivity and specificity are expected to be higher when case/control ascertainment is more definitive and further work is planned to investigate this. Even at the performance levels achieved, the species-neutral DABA has the potential to facilitate the large-scale seroprevalence surveys needed to underpin essential developments in LF control, as well as support zoonotic investigations.

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