Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| lymphocytic choriomeningitis virus (lcmv) infection of macaques: a model for lassa fever. | arenaviruses such as lassa fever virus (lasv) and lymphocytic choriomeningitis virus (lcmv) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (vhf) in non-human primates and in human beings. lcmv is considerably more benign for human beings than lassa virus, however certain strains, like the lcmv-we strain, can cause severe disease when the virus is delivered as a high-dose inoculum. here we describe a rhesus macaque model for lassa fever that ... | 2011 | 21820469 |
| capacity building permitting comprehensive monitoring of a severe case of lassa hemorrhagic fever in sierra leone with a positive outcome: case report. | abstract: lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic west african nations. to date, case reports of lassa fever have focused on laboratory characterisation of serological, biochemical and molecular aspects of the disease imported by infected individuals from western africa to the united states, canada, europe, japan and israel. our report presents the first comprehensive real time diagnosis and characterization of a severe, hemorrha ... | 2011 | 21689444 |
| novel arenavirus sequences in hylomyscus sp. and mus (nannomys) setulosus from c+¦te d'ivoire: implications for evolution of arenaviruses in africa. | this study aimed to identify new arenaviruses and gather insights in the evolution of arenaviruses in africa. during 2003 through 2005, 1,228 small mammals representing 14 different genera were trapped in 9 villages in south, east, and middle west of c+¦te d'ivoire. specimens were screened by pan-old world arenavirus rt-pcrs targeting s and l rna segments as well as immunofluorescence assay. sequences of two novel tentative species of the family arenaviridae, menekre and gbagroube virus, were de ... | 2011 | 21695269 |
| Structure of the Lassa virus nucleoprotein revealed by X-ray crystallography, small-angle X-ray scattering, and electron microscopy. | The nucleoprotein (NP) of Lassa virus (LASV) strain AV was expressed in a recombinant baculovirus system. The crystal structure of full-length NP was solved at a resolution of 2.45 Å. The overall fold corresponds to that of NP of LASV strain Josiah (Qi, X., Lan, S., Wang, W., Schelde, L. M., Dong, H., Wallat, G. D., Ly, H., Liang, Y., and Dong, C. (2010) Nature 468, 779-783) with a root mean square deviation of 0.67 Å for all atoms (6.3% difference in primary sequence). As the packing in the cry ... | 2011 | 21917929 |
| Progress in the experimental therapy of severe arenaviral infections. | A number of viruses in the family Arenaviridae cause severe illness in humans. Lassa virus in West Africa and a number of agents in South America produce hemorrhagic fever in persons exposed to aerosolized excretions of the pathogens' rodent hosts. Because arenaviruses are not transmitted by arthropods, and person-to-person spread is rare, human infections occur singly and sporadically, and are usually not diagnosed until the patient is severely ill. Because the arenaviruses are naturally transm ... | 2011 | 22122440 |
| novel circular, cyclic and acyclic ψ(ch(2)o) containing peptide inhibitors of ski-1/s1p: synthesis, kinetic and biochemical evaluations. | background: subtilisin kexin isozyme-1 (ski-1)/site1protease (s1p) is a ca(+2)-dependent membrane bound pyrolysin-type serine protease of mammalian subtilase super family proprotein convertases (pcs)/proprotein convertase subtilisin kexins (pcsks). it cleaves precursor proteins at the carboxy terminus of a non basic amino acid characterized by the sequence arg/lys-θ-φ-leu/ser/thr↓, where θ = any amino acid except cys, φ = the alkyl side chain containing hydrophobic amino acid. ski-1 cleaves pro- ... | 2011 | 21568902 |
| depletion of gtp pool is not the predominant mechanism by which ribavirin exerts its antiviral effect on lassa virus. | ribavirin (1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is the standard treatment for lassa fever, though its mode of action is unknown. one possibility is depletion of the intracellular gtp pool via inhibition of the cellular enzyme inosine monophosphate dehydrogenase (impdh). this study compared the anti-arenaviral effect of ribavirin with that of two other impdh inhibitors, mycophenolic acid (mpa) and 5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (eicar). all three compounds were ... | 2011 | 21616094 |
| arenavirus reverse genetics: new approaches for the investigation of arenavirus biology and development of antiviral strategies. | several arenaviruses, chiefly lassa virus, cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. on the other hand the prototypic arenavirus lcmv is a superb workhorse for the investigation of virus-host interactions and associated disease. the development of novel antiviral strategies to combat pathogenic arenaviruses would be facilitated by a detailed understanding of the arenavirus molecular and cell biology. to this end, the developm ... | 2011 | 21324503 |
| novel arenavirus, zambia. | to investigate arenavirus in zambia, we characterized virus from the kidneys of 5 arenavirus rna-positive rodents (mastomys natalensis) among 263 captured. full-genome sequences of the viruses suggested that they were new strains similar to lassa virus-related arenaviruses. analyzing samples from additional rodents and other species can elucidate epizootiologic aspects of arenaviruses. | 2011 | 22000372 |
| alix/aip1 is required for np incorporation into mopeia virus z-induced virus-like particles. | during virus particle assembly, the arenavirus nucleoprotein (np) associates with the viral genome to form nucleocapsids, which ultimately become incorporated into new virions at the cell membrane. virion release is facilitated by the viral matrix z protein through its interaction with the cellular endosomal sorting complex required for transport (escrt) machinery. however, the mechanism of nucleocapsid incorporation into virions is not well understood. here, we demonstrate that alix/aip1, an es ... | 2011 | 21248028 |
| structure of the lassa virus nucleoprotein reveals a dsrna-specific 3' to 5' exonuclease activity essential for immune suppression. | lassa fever virus, a member of the family arenaviridae, is a highly endemic category a pathogen that causes 300,000-500,000 infections per year in western africa. the arenaviral nucleoprotein np has been implicated in suppression of the host innate immune system, but the mechanism by which this occurs has remained elusive. here we present the crystal structure at 1.5 å of the immunosuppressive c-terminal portion of lassa virus np and illustrate that, unexpectedly, its 3d fold closely mimics that ... | 2011 | 21262835 |
| inhibition of lassa virus and ebola virus infection in host cells treated with the kinase inhibitors genistein and tyrphostin. | arenaviruses and filoviruses are capable of causing hemorrhagic fever syndrome in humans. limited therapeutic and/or prophylactic options are available for humans suffering from viral hemorrhagic fever. in this report, we demonstrate that pre-treatment of host cells with the kinase inhibitors genistein and tyrphostin ag1478 leads to inhibition of infection or transduction in cells infected with ebola virus, marburg virus, and lassa virus. in all, the results demonstrate that a kinase inhibitor c ... | 2011 | 21947546 |
| early-onset sensorineural hearing loss in lassa fever. | lassa fever (lf) is a viral hemorrhagic disease which affects one-fourth to two million people annually with the fatality rate of about 10,000. it is associated with sensorineural hearing loss (snhl) usually at the convalescent stage. recently, cases of snhl at the acute phase have been reported. this study was done to further investigate the incidence and features of snhl in acute phase of lf. it is a prospective case-control study of lf patients seen with acute snhl conducted between july 2007 ... | 2011 | 20809263 |
| lassa hemorrhagic fever in a late term pregnancy from northern sierra leone with a positive maternal outcome: case report. | abstract: lassa fever (lf) is a devastating viral disease prevalent in west africa. efforts to take on this public health crisis have been hindered by lack of infrastructure and rapid field deployable diagnosis in areas where the disease is prevalent. recent capacity building at the kenema government hospital lassa fever ward (kgh lfw) in sierra leone has lead to a major turning point in the diagnosis, treatment and study of lf. herein we present the first comprehensive rapid diagnosis and real ... | 2011 | 21843352 |
| Progress in recombinant DNA-derived vaccines for Lassa virus and filoviruses. | Developing vaccines for highly pathogenic viruses such as those causing Lassa, Ebola, and Marburg hemorrhagic fevers is a daunting task due to both scientific and logistical constraints. Scientific hurdles to overcome include poorly defined relationships between pathogenicity and protective immune responses, genetic diversity of viruses, and safety in a target population that includes a large number of individuals with compromised immune systems. Logistical obstacles include the requirement for ... | 2011 | 21925552 |
| human dendritic cells infected with the non-pathogenic mopeia virus induce stronger t-cell responses than with lassa virus. | events leading to death in severe cases of lassa fever (lf) are unknown. fatality seems to be linked to high viremia and immunosuppression, with cellular immunity, rather than neutralizing antibodies, appearing to be essential for survival. we previously compared lassa virus (lv) with its genetically close but non pathogenic homolog mopeia virus (mv), which was used to model non fatal lf. we showed that strong and early activation of antigen-presenting cells (apc) may play a crucial role in cont ... | 2011 | 21632749 |
| quantitative analysis of particles, genomes and infectious particles in supernatants of haemorrhagic fever virus cell cultures. | information on the replication of viral haemorrhagic fever viruses is not readily available and has never been analysed in a comparative approach. here, we compared the cell culture growth characteristics of haemorrhagic fever viruses (hfv), of the arenaviridae, filoviridae, bunyaviridae, and flavivridae virus families by performing quantitative analysis of cell culture supernatants by (i) electron microscopy for the quantification of virus particles, (ii) quantitative real time pcr for the quan ... | 2011 | 21349180 |
| arenaviruses and hantaviruses: from epidemiology and genomics to antivirals. | the arenaviruses and hantaviruses are segmented genome rna viruses that are hosted by rodents. due to their association with rodents, they are globally widespread and can infect humans via direct or indirect routes of transmission, causing considerable human morbidity and mortality. nevertheless, despite their obvious and emerging importance as pathogens, there are currently no effective antiviral drugs (except ribavirin which proved effective against lassa virus) with which to treat humans infe ... | 2011 | 21356244 |
| evaluation of lassa antiviral compound st-193 in a guinea pig model. | lassa virus (lasv), a member of the arenaviridae family, causes a viral hemorrhagic fever endemic to west africa, where as many as 300,000 infections occur per year. presently, there are no fda-approved lasv-specific vaccines or antiviral agents, although the antiviral drug ribavirin has shown some efficacy. a recently identified small-molecule inhibitor of arenavirus entry, st-193, exhibits submicromolar antiviral activity in vitro. to determine the antiviral utility of st-193 in vivo, we teste ... | 2011 | 21371508 |
| pathogenesis of lassa fever in cynomolgus macaques. | abstract: | 2011 | 21548931 |
| conserved residues in lassa fever virus z protein modulate viral infectivity at the level of the ribonucleoprotein. | arenaviruses are negative-strand rna viruses that cause human diseases such as lymphocytic choriomeningitis, bolivian hemorrhagic fever, and lassa hemorrhagic fever. no licensed vaccines exist, and current treatment is limited to ribavirin. the prototypic arenavirus, lymphocytic choriomeningitis virus (lcmv), is a model for dissecting virus-host interactions in persistent and acute disease. the ring finger protein z has been identified as the driving force of arenaviral budding and acts as the v ... | 2011 | 21228230 |
| efficient rescue of recombinant lassa virus reveals the influence of s segment noncoding regions on virus replication and virulence. | lassa virus (lasv), is a significant cause of severe, often fatal, hemorrhagic fever in humans throughout western africa, with an estimated 100,000 infections each year. no vaccines are commercially available. we report the development of an efficient reverse genetics system to rescue recombinant lasv and to investigate the contributions of the long 5' and 3' noncoding regions (ncrs) of the s genomic segment to in vitro growth and in vivo virulence. this work demonstrates that deletions of large ... | 2011 | 21307206 |
| [an update on lassa virus]. | lassa virus, the etiologic agent of lassa hemorrhagic fever, infects 100,000 to 300,000 people every year in west africa with an overall mortality rate ranging from 1 to 2%. it was discovered in 1969 and remains a significant public health risk in endemic areas. because airborne transmission is possible and mortality can be high under certain conditions, lassa virus has been classified as a category a bioterrorism agent. early diagnosis is difficult due to insidious non-specific onset and to the ... | 2011 | 22393616 |
| identification of cell surface molecules involved in dystroglycan-independent lassa virus cell entry. | although o-mannosylated dystroglycan is a receptor for lassa virus, a causative agent of lassa fever, recent findings suggest the existence of an alternative receptor(s). here, we identified four molecules as receptors for lassa virus: axl and tyro3, from the tam family and dc-sign and lsectin, from the c-type lectin family. these molecules enhanced lassa virus binding to cells and mediated infection independently of dystroglycan. axl/tyro3-mediated infection required intracellular signaling via ... | 2011 | 22156524 |
| identification of an antioxidant small-molecule with broad-spectrum antiviral activity. | the highly lethal filoviruses, ebola and marburg cause severe hemorrhagic fever in humans and non-human primates. to date there are no licensed vaccines or therapeutics to counter these infections. identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. small molecule chemical screening for ebola virus inhibitors resulted in identification of a compound nsc 62914. the compound was found to exhibit anti-filov ... | 2012 | 22027648 |
| the sensitivity and specificity of lassa virus igm by elisa as screening tool at early phase of lassa fever infection. | early diagnosis, prompt treatment, and disease containment are vital measures in the management of lassa fever (lf), a lethal and contagious arenaviral hemorrhagic disease prevalent in west africa. lassa virus (lav)-specific reverse transcriptase polymerase chain reaction (rt-pcr) test, the gold standard for diagnosis, is unavailable in most centers. serologic detection of lav igm is a more accessible tool and this work was to investigate its adequacy as an early marker for lf. | 2012 | 23661877 |
| vaccine platforms to control arenaviral hemorrhagic fevers. | arenaviruses are rodent-borne emerging human pathogens. diseases caused by these viruses, e.g., lassa fever (lf) in west africa and south american hemorrhagic fevers (hfs), are serious public health problems in endemic areas. we have employed replication-competent and replication-deficient strategies to design vaccine candidates potentially targeting different groups "at risk". our leader lf vaccine candidate, the live reassortant vaccine ml29, is safe and efficacious in all tested animal models ... | 2012 | 23420494 |
| a historical look at the first reported cases of lassa fever: igg antibodies 40 years after acute infection. | lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in west africa. one important question regarding lassa fever is the duration of immunoglobulin g (igg) antibody after infection. we were able to locate three persons who worked in nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of lassa fever in the late 1960s, including the person from whom lassa virus was first isolated. two persons had high titers of ... | 2012 | 23277481 |
| discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole and related heterocycles. | a series of potent arenavirus inhibitors sharing a benzimidazole core were previously reported by our group. sar studies were expanded beyond the previous analysis, which involved the attached phenyl rings and methylamino linker portion, to include modifications focused on the benzimidazole core. these changes included the introduction of various substituents to the bicyclic benzimidazole ring system along with alternate core heterocycles. many of the analogs containing alternate nitrogen-based ... | 2012 | 23265900 |
| structure, function, and evolution of the crimean-congo hemorrhagic fever virus nucleocapsid protein. | crimean-congo hemorrhagic fever virus (cchfv) is an emerging tick-borne virus of the bunyaviridae family that is responsible for a fatal human disease for which preventative or therapeutic measures do not exist. we solved the crystal structure of the cchfv strain baghdad-12 nucleocapsid protein (n), a potential therapeutic target, at a resolution of 2.1 å. n comprises a large globular domain composed of both n- and c-terminal sequences, likely involved in rna binding, and a protruding arm domain ... | 2012 | 22875964 |
| host cell factors as antiviral targets in arenavirus infection. | among the members of the arenaviridae family, lassa virus and junin virus generate periodic annual outbreaks of severe human hemorrhagic fever (hf) in endemic areas of west africa and argentina, respectively. given the human health threat that arenaviruses represent and the lack of a specific and safe chemotherapy, the search for effective antiviral compounds is a continuous demanding effort. since diverse host cell pathways and enzymes are used by rna viruses to fulfill their replicative cycle, ... | 2012 | 23170173 |
| the pi3k/akt pathway contributes to arenavirus budding. | several arenaviruses, chiefly lassa virus (lasv), cause hemorrhagic fever (hf) disease in humans and pose a significant public health concern in regions where they are endemic. on the other hand, evidence indicates that the globally distributed prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) is a neglected human pathogen. the phosphatidylinositol 3-kinase (pi3k)/akt pathway participates in many cellular processes, including cell survival and differentiation, and also has been sho ... | 2012 | 22345463 |
| lassa fever in west africa: evidence for an expanded region of endemicity. | lassa virus (lasv) is endemic in sierra leone, guinea and liberia (known as the mano river region) and nigeria and lassa fever cases from these countries are being reported annually. recent investigations have found evidence for an expanded endemicity zone between the two known lassa endemic regions indicating that lasv is more widely distributed throughout the tropical wooded savanna ecozone in west africa. | 2012 | 22958249 |
| [highly contagious diseases with human-to-human transmission]. | highly contagious diseases are caused by various biological agents that pose a risk to individuals and may have a potential for public health impact. they result in high mortality and morbidity rates, might cause public panic and therefore require special measures. the pathogens that can be easily disseminated or transmitted from person to person are the riskiest for clinicians (ebola virus, marburg virus, lassa virus, crimean-congo hemorrhagic fever virus, variola major, sars virus and yersinia ... | 2012 | 23386507 |
| seroepidemiological study reveals regional co-occurrence of lassa- and hantavirus antibodies in upper guinea, west africa. | to assess the public health relevance of lassa arenavirus and hantavirus infections in a subpopulation of recently febrile patients. | 2012 | 23279760 |
| cell entry of lassa virus induces tyrosine phosphorylation of dystroglycan. | the extracellular matrix (ecm) receptor dystroglycan (dg) serves as a cellular receptor for the highly pathogenic arenavirus lassa virus (lasv) that causes a haemorrhagic fever with high mortality in human. in the host cell, dg provides a molecular link between the ecm and the actin cytoskeleton via the adapter proteins utrophin or dystrophin. here we investigated post-translational modifications of dg in the context of lasv cell entry. using the tyrosine kinase inhibitor genistein, we found tha ... | 2012 | 23279385 |
| discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole. | a chemically diverse library of about 400,000 small molecules was screened for antiviral activity against lentiviral pseudotypes with the lassa virus envelope glycoprotein (lasv gp) gene incorporated. high-throughput screening resulted in discovery of a hit compound (st-37) possessing a benzimidazole core which led to a potent compound series. herein, we report sar studies which involved structural modifications to the phenyl rings and methylamino linker portion attached to the benzimidazole cor ... | 2012 | 23265895 |
| advanced vaccine candidates for lassa fever. | lassa virus (lasv) is the most prominent human pathogen of the arenaviridae. the virus is transmitted to humans by a rodent reservoir, mastomys natalensis, and is capable of causing lethal lassa fever (lf). lasv has the highest human impact of any of the viral hemorrhagic fevers (with the exception of dengue fever) with an estimated several hundred thousand infections annually, resulting in thousands of deaths in western africa. the sizeable disease burden, numerous imported cases of lf in non-e ... | 2012 | 23202493 |
| functional interferon system is required for clearance of lassa virus. | lassa virus (lasv) is the causative agent of lassa hemorrhagic fever (lf) in humans, a deadly disease endemic to west africa that results in 5,000 - 10,000 deaths annually. here we present results demonstrating that functional type i and type ii interferon (ifn) signaling is required for efficient control of lasv dissemination and clearance. | 2012 | 22238311 |
| evaluation of lassa virus vaccine immunogenicity in a cba/j-ml29 mouse model. | lassa fever (lf) is one of the most prevalent viral hemorrhagic fevers in west africa responsible for thousands of deaths annually. the bsl-4 containment requirement and lack of small animal model to evaluate lassa virus (lasv)-specific cell-mediated immunity (cmi) complicate development of effective lf vaccines. here we have described a cba/j-ml29 model allowing evaluation of lasv-specific cmi responses in mice. this model is based on mopeia virus reassortant clone ml29, an attractive immunogen ... | 2012 | 22234266 |
| pathogenic old world arenaviruses inhibit tlr2/mal-dependent proinflammatory cytokines in vitro. | lymphocytic choriomeningitis virus (lcmv), the prototype arenavirus, and lassa virus (lasv), the causative agent of lassa fever (lf), have extensive strain diversity and significant variations in pathogenicity for humans and experimental animals. the we strain of lcmv (lcmv-we), but not the armstrong (arm) strain, induces a fatal lf-like disease in rhesus macaques. we also demonstrated that lasv infection of human macrophages and endothelial cells resulted in reduced levels of proinflammatory cy ... | 2012 | 22532679 |
| binding of lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan. | the arenavirus lassa virus (lasv) causes a severe haemorrhagic fever with high mortality in man. the cellular receptor for lasv is dystroglycan (dg). dg is a ubiquitous receptor for extracellular matrix (ecm) proteins, which cooperates with β1 integrins to control cell-matrix interactions. here, we investigated whether lasv binding to dg triggers signal transduction, mimicking the natural ligands. engagement of dg by lasv resulted in the recruitment of the adaptor protein grb2 and the protein ki ... | 2012 | 22405130 |
| molecular characterization of the processing of arenavirus envelope glycoprotein precursors by subtilisin kexin isozyme-1/site-1 protease. | a crucial step in the life cycle of arenaviruses is the biosynthesis of the mature fusion-active viral envelope glycoprotein (gp) that is essential for virus-host cell attachment and entry. the maturation of the arenavirus gp precursor (gpc) critically depends on proteolytic processing by the cellular proprotein convertase (pc) subtilisin kexin isozyme-1 (ski-1)/site-1 protease (s1p). here we undertook a molecular characterization of the ski-1/s1p processing of the gpcs of the prototypic arenavi ... | 2012 | 22357276 |
| genome-wide scans provide evidence for positive selection of genes implicated in lassa fever. | rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. with the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. based on this approach, we have previously hypothesized that lassa virus (lasv) may have been a driver of natural selecti ... | 2012 | 22312054 |
| self-association of lymphocytic choriomeningitis virus nucleoprotein is mediated by its n-terminal region and is not required for its anti-interferon function. | arenaviruses have a bisegmented, negative-strand rna genome. both the large (l) and small (s) genome segments use an ambisense coding strategy to direct the synthesis of two viral proteins. the l segment encodes the virus polymerase (l protein) and the matrix z protein, whereas the s segment encodes the nucleoprotein (np) and the glycoprotein precursor (gpc). nps are the most abundant viral protein in infected cells and virions and encapsidate genomic rna species to form an np-rna complex that, ... | 2012 | 22258244 |
| [arenavirus infections]. | arenaviruses are the collective name for viruses, which belong to the family arenaviridae. they replicate in the cytoplasm of cells, and were named after the sandy (latin, arenosus) appearance of the ribosomes often seen in thin sections of virions under electron microscope. several arenaviruses, such as lassa virus in west africa, and junin, guanarito, sabia, machupo, and chapare viruses in south america, cause sever viral hemorrhagic fevers (vhf) in humans and represent a serious public health ... | 2012 | 24153233 |
| immune responses and lassa virus infection. | lassa fever is a hemorrhagic fever endemic to west africa and caused by lassa virus, an old world arenavirus. it may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. the immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immu ... | 2012 | 23202504 |
| pathogenesis of lassa fever. | lassa virus, an old world arenavirus (family arenaviridae), is the etiological agent of lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of west africa with mortality rates for hospitalized patients varying between 5-10%. currently, there are no approved vaccines against lassa fever for use in humans. here, we review the published literature on the life cycle of lassa virus with the specific focus put on lassa fever pathogenesis i ... | 2012 | 23202452 |
| molecular diagnostics for lassa fever at irrua specialist teaching hospital, nigeria: lessons learnt from two years of laboratory operation. | lassa fever is a viral hemorrhagic fever endemic in west africa. however, none of the hospitals in the endemic areas of nigeria has the capacity to perform lassa virus diagnostics. case identification and management solely relies on non-specific clinical criteria. the irrua specialist teaching hospital (isth) in the central senatorial district of edo state struggled with this challenge for many years. | 2012 | 23029594 |
| structural basis for the dsrna specificity of the lassa virus np exonuclease. | lassa virus causes hemorrhagic fever characterized by immunosuppression. the nucleoprotein of lassa virus, termed np, binds the viral genome. it also has an additional enzymatic activity as an exonuclease that specifically digests double-stranded rna (dsrna). dsrna is a strong signal to the innate immune system of viral infection. digestion of dsrna by the np exonuclease activity appears to cause suppression of innate immune signaling in the infected cell. although the fold of the np enzyme is c ... | 2012 | 22937163 |
| cell surface molecules involved in infection mediated by lymphocytic choriomeningitis virus glycoprotein. | the glycoprotein (gp) of lymphocytic choriomeningitis virus (lcmv), the prototype arenavirus, is a promising envelope protein of lentiviral pseudotype vectors for gene therapy. the distribution of dystroglycan, a known receptor for lcmv, cannot explain the narrow tropism of lcmv-gp-pseudotypes. here, we examined whether infection of lcmv-gp-pseudotypes was affected by the expression of four cell surface molecules-axl and tyro3 (from the tam family) and dc-sign and lsectin (from the c-type lectin ... | 2012 | 22673088 |
| the impact of human conflict on the genetics of mastomys natalensis and lassa virus in west africa. | environmental changes have been shown to play an important role in the emergence of new human diseases of zoonotic origin. the contribution of social factors to their spread, especially conflicts followed by mass movement of populations, has not been extensively investigated. here we reveal the effects of civil war on the phylogeography of a zoonotic emerging infectious disease by concomitantly studying the population structure, evolution and demography of lassa virus and its natural reservoir, ... | 2012 | 22615894 |
| hospital-based surveillance for lassa fever in edo state, nigeria, 2005-2008. | to estimate the burden of lassa fever in northern and central edo, a state in south nigeria where lassa fever has been reported. | 2012 | 22594713 |
| nk cells are strongly activated by lassa and mopeia virus-infected human macrophages in vitro but do not mediate virus suppression. | lassa virus (lasv) and mopeia virus (mopv) are closely related arenaviruses. lasv causes hemorrhagic fever, whereas mopv is not pathogenic. both viruses display tropism for apcs such as dcs and macrophages. during viral infections, nk cells are involved in the clearance of infected cells and promote optimal immune responses by interacting with apcs. we used an in vitro model of human nk and apc coculture to study the role of nk cells and to characterize their interactions with apcs during lasv a ... | 2012 | 22585682 |
| rapid and specific detection of lassa virus by reverse transcription-pcr coupled with oligonucleotide array hybridization. | to facilitate sequence-specific detection of dna amplified in a diagnostic reverse transcription (rt)-pcr for lassa virus, we developed an array featuring 47 oligonucleotide probes for post-pcr hybridization of the amplicons. the array procedure may be performed with low-tech equipment and does not take longer than agarose gel detection. | 2012 | 22535985 |
| plasmacytoid dendritic cells are productively infected and activated through tlr-7 early after arenavirus infection. | the antiviral response is largely mediated by dendritic cells (dcs), including conventional (c) dcs that function as antigen-presenting cells, and plasmacytoid (p) dcs that produce type i interferons, making them an attractive target for viruses. we find that the old world arenaviruses lymphocytic choriomeningitis virus clone 13 (lcmv cl13) and lassa virus bind pdcs to a greater extent than cdcs. consistently, lcmv cl13 targets pdcs early after in vivo infection of its natural murine host and es ... | 2012 | 22704622 |
| studies on the binding modes of lassa nucleoprotein complexed with m7gpppg and dttp by molecular dynamic simulations and free energy calculations. | lassa virus can cause dreadful human hemorrhagic disease, for which there is no effective therapy. a recent study points out that the amino (n)-terminal domain of lassa virus nucleoprotein (np) plays an important role in viral rna synthesis and firstly solved the x-ray crystal structures of np complexed with the capped deoxythymidine triphosphate (dttp) analog, but the binding mode of m7gpppg to the n domain of np, which is required for viral rna transcription, has not been studied. in this stud ... | 2013 | 22871039 |
| density thresholds for mopeia virus invasion and persistence in its host mastomys natalensis. | well-established theoretical models predict host density thresholds for invasion and persistence of parasites with a density-dependent transmission. studying such thresholds in reality, however, is not obvious because it requires long-term data for several fluctuating populations of different size. we developed a spatially explicit and individual-based seir model of mopeia virus in multimammate mice mastomys natalensis. this is an interesting model system for studying abundance thresholds becaus ... | 2013 | 23041432 |
| lead optimization of an acylhydrazone scaffold possessing antiviral activity against lassa virus. | previously we reported the optimization of antiviral scaffolds containing benzimidazole and related heterocycles possessing activity against a variety of arenaviruses. these series of compounds were discovered through an hts campaign of a 400,000 small molecule library using lentivirus-based pseudotypes incorporated with the lassa virus envelope glycoprotein (lasv gp). this screening also uncovered an alternate series of very potent arenavirus inhibitors based upon an acylhydrazone scaffold. sub ... | 2013 | 24064500 |
| infection of type i interferon receptor-deficient mice with various old world arenaviruses: a model for studying virulence and host species barriers. | lassa virus causes hemorrhagic lassa fever in humans, while the related old world arenaviruses mopeia, morogoro, and mobala are supposedly apathogenic to humans and cause only inapparent infection in non-human primates. here, we studied whether the virulence of old world arenaviruses in humans and non-human primates is reflected in type i interferon receptor deficient (ifnar(-/-)) mice by testing several strains of lassa virus vs. the apathogenic viruses mopeia, morogoro, and mobala. all lassa v ... | 2013 | 23991083 |
| mice lacking functional stat1 are highly susceptible to lethal infection with lassa virus. | lassa fever (lf) is a potentially lethal human disease that is caused by the arenavirus lassa virus (lasv). annually, around 300,000 infections with up to 10,000 deaths occur in regions of lassa fever endemicity in west africa. here we demonstrate that mice lacking a functional stat1 pathway are highly susceptible to infection with lasv and develop lethal disease with pathology similar to that reported in humans. | 2013 | 23903830 |
| pathogenesis of lassa fever virus infection: i. susceptibility of mice to recombinant lassa gp/lcmv chimeric virus. | lassa virus (lasv) is a bsl-4 restricted agent. to allow study of infection by lasv under bsl-2 conditions, we generated a recombinant virus in which the lasv glycoprotein (gp) was placed on the backbone of lymphocytic choriomeningitis virus (lcmv) cl13 nucleoprotein, z and polymerase genes (rlcmv cl13/lasv gp). the recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. inoculation of immunocompetent adults resulted in an acute infection, generation ... | 2013 | 23684417 |
| transcriptional profiling of the circulating immune response to lassa virus in an aerosol model of exposure. | lassa virus (lasv) is a significant human pathogen that is endemic to several countries in west africa. infection with lasv leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. little is known about the complex immune mechanisms governing the response to lasv or the genetic determinants of susceptibility and resistance to infection. in the study presented here, we have used a whole-genome, microarray-ba ... | 2013 | 23638192 |
| structures of arenaviral nucleoproteins with triphosphate dsrna reveal a unique mechanism of immune suppression. | a hallmark of severe lassa fever is the generalized immune suppression, the mechanism of which is poorly understood. lassa virus (lasv) nucleoprotein (np) is the only known 3'-5' exoribonuclease that can suppress type i interferon (ifn) production possibly by degrading immune-stimulatory rnas. how this unique enzymatic activity of lasv np recognizes and processes rna substrates is unknown. we provide an atomic view of a catalytically active exoribonuclease domain of lasv np (lasv np-c) in the pr ... | 2013 | 23615902 |
| the role of oligomerization for the biological functions of the arenavirus nucleoprotein. | the lassa virus nucleoprotein (np) is a multifunctional protein that plays an essential role in many aspects of the viral life cycle, including rna encapsidation, viral transcription and replication, recruitment of ribonucleoprotein complexes to viral budding sites, and inhibition of the host cell interferon response. while it is known that np is capable of forming oligomers, both the oligomeric state of np in mammalian cells and the significance of np oligomerization for its various functions r ... | 2013 | 23553456 |
| housing equity for health equity: a rights-based approach to the control of lassa fever in post-war sierra leone. | poor quality housing is an infringement on the rights of all humans to a standard of living adequate for health. among the many vulnerabilities of those without adequate shelter is the risk of disease spread by rodents and other pests. one such disease is lassa fever, an acute and sometimes severe viral hemorrhagic illness endemic in west africa. lassa virus is maintained in the rodent mastomys natalensis, commonly known as the "multimammate rat," which frequently invades the domestic environmen ... | 2013 | 23282054 |
| the microtubule motor protein kif13a is involved in intracellular trafficking of the lassa virus matrix protein z. | the small matrix protein z of arenaviruses has been identified as the main driving force to promote viral particle production at the plasma membrane. although multiple functions of z in the arenaviral life cycle have been uncovered, the mechanism of intracellular transport of z to the site of virus budding is poorly understood and cellular motor proteins that mediate z trafficking remain to be identified. in the present study, we report that the z protein of the old world arenavirus lassa virus ... | 2013 | 23279019 |
| targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever. | a number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. lassa virus, found in west africa, causes severe hemorrhagic fever (hf), while the other principal old world arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. the new world agents, including junin, machupo and sabia virus, are highly pathogenic for humans. arenaviral hf is characterized ... | 2013 | 23261843 |
| the role of proteolytic processing and the stable signal peptide in expression of the old world arenavirus envelope glycoprotein ectodomain. | maturation of the arenavirus gp precursor (gpc) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (ski-1)/site 1 protease (s1p), yielding a tripartite complex comprised of a stable signal peptide (ssp), the receptor-binding gp1, and the fusion-active transmembrane gp2. here we investigated the roles of ski-1/s1p processing and ssp in the biosynthesis of the recombinant gp ectodomains of lymphocytic choriomeningitis virus (lcmv) ... | 2013 | 23218200 |
| two novel arenaviruses detected in pygmy mice, ghana. | two arenaviruses were detected in pygmy mice (mus spp.) by screening 764 small mammals in ghana. the natal multimammate mouse (mastomys natalensis), the known lassa virus reservoir, was the dominant indoor rodent species in 4 of 10 sites, and accounted for 27% of all captured rodents. no rodent captured indoors tested positive for an arenavirus. | 2013 | 24188212 |
| transcriptome analysis of human peripheral blood mononuclear cells exposed to lassa virus and to the attenuated mopeia/lassa reassortant 29 (ml29), a vaccine candidate. | lassa virus (lasv) is the causative agent of lassa fever and is responsible for several hundred thousand infections and thousands of deaths annually in west africa. lasv and the non-pathogenic mopeia virus (mopv) are both rodent-borne african arenaviruses. a live attenuated reassortant of mopv and lasv, designated ml29, protects rodents and primates from lasv challenge and appears to be more attenuated than mopv. to gain better insight into lasv-induced pathology and mechanism of attenuation we ... | 2013 | 24069471 |
| identification of virulence determinants within the l genomic segment of the pichinde arenavirus. | several arenaviruses are responsible for causing viral hemorrhagic fevers (vhf) in humans. lassa virus (lasv), the causative agent of lassa fever, is a biosafety level 4 (bsl4) pathogen that requires handling in bsl4 facilities. in contrast, the pichinde arenavirus (picv) is a bsl2 pathogen that can cause hemorrhagic fever-like symptoms in guinea pigs that resemble those observed in human lassa fever. comparative sequence analysis of the avirulent p2 strain of picv and the virulent p18 strain sh ... | 2013 | 23552411 |
| differential recognition of old world and new world arenavirus envelope glycoproteins by subtilisin kexin isozyme 1 (ski-1)/site 1 protease (s1p). | the arenaviruses are an important family of emerging viruses that includes several causative agents of severe hemorrhagic fevers in humans that represent serious public health problems. a crucial step of the arenavirus life cycle is maturation of the envelope glycoprotein precursor (gpc) by the cellular subtilisin kexin isozyme 1 (ski-1)/site 1 protease (s1p). comparison of the currently known sequences of arenavirus gpcs revealed the presence of a highly conserved aromatic residue at position p ... | 2013 | 23536681 |
| deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry. | glycosylated α-dystroglycan (α-dg) serves as cellular entry receptor for multiple pathogens, and defects in its glycosylation cause hereditary walker-warburg syndrome (wws). at least eight proteins are critical to glycosylate α-dg, but many genes mutated in wws remain unknown. to identify modifiers of α-dg, we performed a haploid screen for lassa virus entry, a hemorrhagic fever virus causing thousands of deaths annually that hijacks glycosylated α-dg to enter cells. in complementary screens, we ... | 2013 | 23519211 |
| a historical look at the first reported cases of lassa fever: igg antibodies 40 years after acute infection. | lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in west africa. one important question regarding lassa fever is the duration of immunoglobulin g (igg) antibody after infection. we were able to locate three persons who worked in nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of lassa fever in the late 1960s, including the person from whom lassa virus was first isolated. two persons had high titers of ... | 2013 | 23390223 |
| a recently isolated lassa virus from mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques. | the virulence of soromba-r, a lassa virus strain recently isolated from southern mali, was assessed in 2 animal models of lassa fever: inbred strain 13 guinea pigs and cynomolgus macaques. in both models, the malian isolate demonstrated tissue tropism and viral titers similar to those of historical lassa virus isolates from sierra leone (josiah) and liberia (z-132); however, the soromba-r isolate was found to be less pathogenic, as determined by decreased mortality and prolonged time to euthanas ... | 2013 | 23303805 |
| geographic distribution and genetic characterization of lassa virus in sub-saharan mali. | lassa fever is an acute viral illness characterized by multi-organ failure and hemorrhagic manifestations. lassa fever is most frequently diagnosed in nigeria, sierra leone, liberia, and guinea, although sporadic cases have been recorded in other west african countries, including mali. the etiological agent of lassa fever is lassa virus (lasv), an arenavirus which is maintained in nature and frequently transmitted to humans by mastomys natalensis. the purpose of this study was to better define t ... | 2013 | 24340119 |
| enhanced efficacy of a codon-optimized dna vaccine encoding the glycoprotein precursor gene of lassa virus in a guinea pig disease model when delivered by dermal electroporation. | lassa virus (lasv) causes a severe, often fatal, hemorrhagic fever endemic to west africa. presently, there are no fda-licensed medical countermeasures for this disease. in a pilot study, we constructed a dna vaccine (plasv-gpc) that expressed the lasv glycoprotein precursor gene (gpc). this plasmid was used to vaccinate guinea pigs (gps) using intramuscular electroporation as the delivery platform. vaccinated gps were protected from lethal infection (5/6) with lasv compared to the controls. how ... | 2013 | 26344112 |
| an attenuated lassa vaccine in siv-infected rhesus macaques does not persist or cause arenavirus disease but does elicit lassa virus-specific immunity. | lassa hemorrhagic fever (lhf) is a rodent-borne viral disease that can be fatal for human beings. in this study, an attenuated lassa vaccine candidate, ml29, was tested in siv-infected rhesus macaques for its ability to elicit immune responses without instigating signs pathognomonic for arenavirus disease. ml29 is a reassortant between lassa and mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal lassa viral challenge. however, si ... | 2013 | 23402317 |
| intervention strategies for emerging viruses: use of antivirals. | today, small molecule antiviral drugs are available for the treatment of infections with herpesviruses, hiv, hbv and hcv as well as with influenza viruses. ribavirin, a broad-spectrum (but aspecific) antiviral, has been approved for the treatment of infections with respiratory syncytial virus, hcv and lassa virus. yet, for many other viruses that cause life-threatening infections [most of which are considered emerging and/or neglected] there are no drugs available. ideally, potent and broad-spec ... | 2013 | 23562753 |
| role of dc-sign in lassa virus entry into human dendritic cells. | the arenavirus lassa virus (lasv) causes a severe hemorrhagic fever with high mortality in humans. antigen-presenting cells, in particular dendritic cells (dcs), are early and preferred targets of lasv, and their productive infection contributes to the virus-induced immunosuppression observed in fatal disease. here, we characterized the role of the c-type lectin dc-specific icam-3-grabbing nonintegrin (dc-sign) in lasv entry into primary human dcs using a chimera of the prototypic arenavirus lym ... | 2013 | 23966408 |
| sodium hydrogen exchangers contribute to arenavirus cell entry. | several arenaviruses, chiefly lassa virus (lasv), cause hemorrhagic fever (hf) disease in humans and pose a great public health concern in the regions in which they are endemic. moreover, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) is a neglected human pathogen of clinical significance. the limited existing armamentarium to combat human-pathogenic arenaviruses underscores the importance of developing novel antiarenaviral drugs ... | 2013 | 24173224 |
| vaccines for viral hemorrhagic fevers--progress and shortcomings. | with a few exceptions, vaccines for viruses that cause hemorrhagic fever remain unavailable or lack well-documented efficacy. in the past decade this has not been due to a lack of the ability to develop vaccine platforms against highly pathogenic viruses, but rather the lack of will/interest to invest in platforms that have the potential to become successful vaccines. the two exceptions to this are vaccines against dengue virus (denv) and rift valley fever virus (rvfv), which recently have seen ... | 2013 | 23773330 |
| high-resolution structure of the n-terminal endonuclease domain of the lassa virus l polymerase in complex with magnesium ions. | lassa virus (lasv) causes deadly hemorrhagic fever disease for which there are no vaccines and limited treatments. lasv-encoded l polymerase is required for viral rna replication and transcription. the functional domains of l-a large protein of 2218 amino acid residues-are largely undefined, except for the centrally located rna-dependent rna polymerase (rdrp) motif. recent structural and functional analyses of the n-terminal region of the l protein from lymphocytic choriomeningitis virus (lcmv), ... | 2014 | 24516554 |
| high content image-based screening of a protease inhibitor library reveals compounds broadly active against rift valley fever virus and other highly pathogenic rna viruses. | high content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against rift valley fever virus (rvfv) and to determine their mechanism of action. rvfv is the causative agent of severe disease of humans and animals throughout africa and the arabian peninsula. of the 849 compounds screened, 34 compounds exhibited ≥ 50% inhibition against rvfv. all of the hit compounds could be classified into 4 distinct groups based on the ... | 2014 | 25144302 |
| comparative analysis of disease pathogenesis and molecular mechanisms of new world and old world arenavirus infections. | arenaviruses can cause fatal human haemorrhagic fever (hf) diseases for which vaccines and therapies are extremely limited. both the new world (nw) and old world (ow) groups of arenaviruses contain hf-causing pathogens. although these two groups share many similarities, important differences with regard to pathogenicity and molecular mechanisms of virus infection exist. these closely related pathogens share many characteristics, including genome structure, viral assembly, natural host selection ... | 2014 | 24068704 |
| analysis of determinants in filovirus glycoproteins required for tetherin antagonism. | the host cell protein tetherin can restrict the release of enveloped viruses from infected cells. the hiv-1 protein vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of vpu and tetherin. in contrast, the glycoproteins (gps) of two filoviruses, ebola and marburg virus, antagonize tetherin without reducing surface expression, and the domains in gp required for tetherin cou ... | 2014 | 24721789 |
| a comparative high-throughput screening protocol to identify entry inhibitors of enveloped viruses. | emerging and reemerging human viral pathogens pose great public health concerns since therapeutics against these viruses are limited. thus, there is an urgent need to develop novel drugs that can block infection of either a specific virus or a number of viruses. viral entry is thought to be an ideal target for potential therapeutic prevention. one of the challenges of developing antivirals is that most of these viruses are highly pathogenic and therefore require high biosafety-level containment. ... | 2014 | 23821643 |
| inhibition of arenavirus infection by a glycoprotein-derived peptide with a novel mechanism. | the family arenaviridae includes a number of viruses of public health importance, such as the category a hemorrhagic fever viruses lassa virus, junin virus, machupo virus, guanarito virus, and sabia virus. current chemotherapy for arenavirus infection is limited to the nucleoside analogue ribavirin, which is characterized by considerable toxicity and treatment failure. using pichinde virus as a model arenavirus, we attempted to design glycoprotein-derived fusion inhibitors similar to the fda-app ... | 2014 | 24850726 |
| lassa fever - full recovery without ribavarin treatment: a case report. | lassa fever is a rodent-borne zoonosis that clinically manifests as an acute hemorrhagic fever. it is treated using ribavarin. surviving lassa fever without receiving the antiviral drug ribavarin is rare. only few cases have been documented to date. | 2014 | 25834520 |
| the rubber plantation environment and lassa fever epidemics in liberia, 2008-2012: a spatial regression. | as lassa fever continues to be a public health challenge in west africa, it is critical to produce good maps of its risk pattern for use in active surveillance and control intervention. we identified eight spatial features related to the rubber plantation environment and used them as explanatory variables for lassa fever (lf) outbreaks on the uniroyal liberian agricultural company (lac) rubber plantation environment in grand bassa county, liberia. we computed classical and spatial lag regression ... | 2014 | 25457605 |
| clinical features and patient management of lujo hemorrhagic fever. | in 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, lujo virus, occurred in johannesburg, south africa. lujo virus is only the second pathogenic arenavirus, after lassa virus, to be recognized in africa and the first in over 40 years. because of the remote, resource-poor, and often politically unstable regions where lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their c ... | 2014 | 25393244 |
| exonuclease domain of the lassa virus nucleoprotein is critical to avoid rig-i signaling and to inhibit the innate immune response. | lassa virus (lasv), which causes a viral hemorrhagic fever, inhibits the innate immune response. the exonuclease (exon) domain of its nucleoprotein (np) is implicated in the suppression of retinoic acid-inducible gene i (rig-i) signaling. we show here that a lasv in which exon function has been abolished strongly activates innate immunity and that this effect is dependent on rig-i signaling. these results highlight the key role of np exon function in the immune evasion that occurs during lasv in ... | 2014 | 25253344 |
| genetic variation in vitro and in vivo of an attenuated lassa vaccine candidate. | the attenuated lassa vaccine candidate ml29 is a laboratory-produced reassortant between lassa and mopeia viruses, two old world arenaviruses that differ by 40% in nucleic acid sequence. in our previous studies, ml29 elicited sterilizing immunity against lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (siv)-infected and uninfected rhesus macaques. here, we show that ml29 is stable after 12 passages in vitro withou ... | 2014 | 24335292 |
| lassa and marburg viruses elicit distinct host transcriptional responses early after infection. | lassa virus and marburg virus are two causative agents of viral hemorrhagic fever. their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. using the transcriptional response of the host during infection can lead to ... | 2014 | 25377889 |
| lassa fever in post-conflict sierra leone. | lassa fever (lf), an often-fatal hemorrhagic disease caused by lassa virus (lasv), is a major public health threat in west africa. when the violent civil conflict in sierra leone (1991 to 2002) ended, an international consortium assisted in restoration of the lf program at kenema government hospital (kgh) in an area with the world's highest incidence of the disease. | 2014 | 24651047 |
| production of cxc and cc chemokines by human antigen-presenting cells in response to lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with lassa fever. | the pathogenesis of lassa fever (lf), a hemorrhagic fever endemic to west africa, remains unclear. we previously compared lassa virus (lasv) with its genetically close, but nonpathogenic homolog mopeia virus (mopv) and demonstrated that the strong activation of antigen-presenting cells (apc), including type i ifn production, observed in response to mopv probably plays a crucial role in controlling infection. we show here that human macrophages (mp) produce large amounts of cc and cxc chemokines ... | 2014 | 24421914 |
| the exonuclease domain of lassa virus nucleoprotein is involved in antigen-presenting-cell-mediated nk cell responses. | lassa virus is an old world arenavirus which causes lassa hemorrhagic fever in humans, mostly in west africa. lassa fever is an important public health problem, and a safe and effective vaccine is urgently needed. the infection causes immunosuppression, probably due to the absence of activation of antigen-presenting cells (dendritic cells and macrophages), low type i interferon (ifn) production, and deficient nk cell function. however, a recombinant lassa virus carrying d389a and g392a substitut ... | 2014 | 25253342 |
| lassa serology in natural populations of rodents and horizontal transmission. | lassa virus causes hemorrhagic fever in west africa. previously, we demonstrated by pcr screening that only the multimammate mouse, mastomys natalensis, hosts lassa virus in guinea. in the present study, we used the same specimen collection from 17 villages in coastal, upper, and forest guinea to investigate the lassa virus serology in the rodent population. the aim was to determine the dynamics of antibody development in m. natalensis and to detect potential spillover infections in other rodent ... | 2014 | 25229705 |
| mapping transmission risk of lassa fever in west africa: the importance of quality control, sampling bias, and error weighting. | lassa fever is a disease that has been reported from sites across west africa; it is caused by an arenavirus that is hosted by the rodent m. natalensis. although it is confined to west africa, and has been documented in detail in some well-studied areas, the details of the distribution of risk of lassa virus infection remain poorly known at the level of the broader region. in this paper, we explored the effects of certainty of diagnosis, oversampling in well-studied region, and error balance on ... | 2014 | 25105746 |