Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| lassa fever, nigeria, 2005-2008. | 2010 | 20507773 | |
| development and evaluation of a simple assay for marburg virus detection using a reverse transcription-loop-mediated isothermal amplification method. | marburg virus (marv) causes a severe hemorrhagic fever in humans with a high mortality rate. the rapid and accurate identification of the virus is required to appropriately provide infection control and outbreak management. here, we developed and evaluated a one-step reverse transcription-loop-mediated isothermal amplification (rt-lamp) assay for the rapid and simple detection of marv. by combining two sets of primers specific for the musoke and ravn genetic lineages, a multiple rt-lamp assay de ... | 2010 | 20421440 |
| t cell-dependence of lassa fever pathogenesis. | lassa virus (lasv), the causative agent of lassa fever (lf), is endemic in west africa, accounting for substantial morbidity and mortality. in spite of ongoing research efforts, lf pathogenesis and mechanisms of lasv immune control remain poorly understood. while normal laboratory mice are resistant to lasv, we report that mice expressing humanized instead of murine mhc class i (mhc-i) failed to control lasv infection and develop severe lf. infection of mhc-i knockout mice confirmed a key role f ... | 2010 | 20360949 |
| improved detection of lassa virus by reverse transcription-pcr targeting the 5' region of s rna. | the method of choice for the detection of lassa virus is reverse transcription (rt)-pcr. however, the high degree of genetic variability of the virus poses a problem with the design of rt-pcr assays that will reliably detect all strains. recently, we encountered difficulties in detecting some strains from liberia and nigeria in a commonly used glycoprotein precursor (gpc) gene-specific rt-pcr assay (a. h. demby, j. chamberlain, d. w. brown, and c. s. clegg, j. clin. microbiol. 32:2898-2903, 1994 ... | 2010 | 20351210 |
| a role for the c terminus of mopeia virus nucleoprotein in its incorporation into z protein-induced virus-like particles. | arenaviruses are enveloped, negative-strand rna viruses. for several arenaviruses, virus-like particle (vlp) formation requires the viral matrix z protein. however, the mechanism by which viral ribonucleoprotein complexes are incorporated into virions is poorly understood. here, we show that the expression of the z protein and nucleoprotein (np) of mopeia virus, a close relative of the pathogenic lassa virus, resulted in the highly selective incorporation of the np protein into z protein-induced ... | 2010 | 20200234 |
| viral protein determinants of lassa virus entry and release from polarized epithelial cells. | the epithelium plays a key role in the spread of lassa virus. transmission from rodents to humans occurs mainly via inhalation or ingestion of droplets, dust, or food contaminated with rodent urine. here, we investigated lassa virus infection in cultured epithelial cells and subsequent release of progeny viruses. we show that lassa virus enters polarized madin-darby canine kidney (mdck) cells mainly via the basolateral route, consistent with the basolateral localization of the cellular lassa vir ... | 2010 | 20071570 |
| an n-terminal region of lassa virus l protein plays a critical role in transcription but not replication of the virus genome. | the central domain of the 200-kda lassa virus l protein is a putative rna-dependent rna polymerase. n- and c-terminal domains may harbor enzymatic functions important for viral mrna synthesis, including capping enzymes or cap-snatching endoribonucleases. in the present study, we have employed a large-scale mutagenesis approach to map functionally relevant residues in these regions. the main targets were acidic (asp and glu) and basic residues (lys and arg) known to form catalytic and binding sit ... | 2010 | 20007273 |
| z proteins of new world arenaviruses bind rig-i and interfere with type i interferon induction. | the retinoic acid-inducible gene i product (rig-i) is a cellular sensor of rna virus infection that regulates the cellular beta interferon (ifn-beta) response. the nucleoproteins (np) of arenaviruses are reported to antagonize the ifn response by inhibiting interferon regulatory factor 3 (irf-3). here, we demonstrate that the z proteins of four new world (nw) arenaviruses, guanarito virus (gtov), junin virus (junv), machupo virus (mavc), and sabia virus (sabv), bind to rig-i, resulting in downre ... | 2010 | 20007272 |
| the role of the vascular endothelium in arenavirus haemorrhagic fevers. | viral haemorrhagic fevers (vhf) caused by arenaviruses are among the most devastating emerging human diseases. the most important pathogen among the arenaviruses is lassa virus (lasv), the causative agent of lassa fever that is endemic to west africa. on the south american continent, the new world arenavirus junin virus (junv), machupo (macv), guanarito (gtov), and sabia virus (sabv) have emerged as causative agents of severe vhfs. clinical and experimental studies on arenavirus vhf have reveale ... | 2009 | 19967131 |
| attenuated and lethal variants of pichindé virus induce differential patterns of nf-kappab activation suggesting a potential target for novel therapeutics. | lassa virus pathogenesis is believed to involve dysregulation of cytokines. we have previously shown nuclear factor-kappab (nf-kappab) inhibition using a bsl-2 model for lassa fever. here we further define the potential mechanism for nf-kappab inhibition as involving increased levels of repressive p50/p50 homodimers, and suggest a novel therapeutic strategy that acts via modulation of host signaling. | 2009 | 19951183 |
| prevalence and risk factors of lassa seropositivity in inhabitants of the forest region of guinea: a cross-sectional study. | lassa fever is a viral hemorrhagic fever endemic in west africa. the reservoir host of the virus is a multimammate rat, mastomys natalensis. prevalence estimates of lassa virus antibodies in humans vary greatly between studies, and the main modes of transmission of the virus from rodents to humans remain unclear. we aimed to (i) estimate the prevalence of lassa virus-specific igg antibodies (lv igg) in the human population of a rural area of guinea, and (ii) identify risk factors for positive lv ... | 2009 | 19924222 |
| characterization of lassa virus glycoprotein oligomerization and influence of cholesterol on virus replication. | mature glycoprotein spikes are inserted in the lassa virus envelope and consist of the distal subunit gp-1, the transmembrane-spanning subunit gp-2, and the signal peptide, which originate from the precursor glycoprotein pre-gp-c by proteolytic processing. in this study, we analyzed the oligomeric structure of the viral surface glycoprotein. chemical cross-linking studies of mature glycoprotein spikes from purified virus revealed the formation of trimers. interestingly, sucrose density gradient ... | 2010 | 19889753 |
| characterization of the lassa virus gp1 ectodomain shedding: implications for improved diagnostic platforms. | there is a significant requirement for the development and acquisition of reagents that will facilitate effective diagnosis, treatment, and prevention of lassa fever. in this regard, detection of early markers of lassa virus (lasv) infection may improve diagnosis and ultimately successful treatment with antivirals. characterization of lasv gp1 ectodomain shedding is an important step toward developing sensitive diagnostics to detect circulating levels of this viral glycoprotein in infected patie ... | 2009 | 19778448 |
| molecular and cell biology of the prototypic arenavirus lcmv: implications for understanding and combating hemorrhagic fever arenaviruses. | arenaviruses merit interest as experimental model systems to study virus-host interactions and as clinically important human pathogens. several arenaviruses, chiefly lassa virus (lasv), cause hemorrhagic fever (hf) in humans. in addition, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) is a neglected human pathogen. moreover, arenaviruses pose a biodefense threat. no licensed arenavirus vaccines are available, and current therapy ... | 2009 | 19751403 |
| dimerization of tetherin is not essential for its antiviral activity against lassa and marburg viruses. | tetherin (also known as bst2, cd317 or hm1.24) has recently been reported to inhibit a wide range of viruses. however, the antiviral mechanism of action of tetherin has not been determined. both ends of the tetherin molecule are associated with the plasma membrane and it forms a homodimer. therefore, a model in which progeny virions are retained on the cell surface by dimer formation between tetherin molecules on the viral envelope and plasma membrane has been proposed as the antiviral mechanism ... | 2009 | 19742323 |
| change in blood test after irradiation with high doses for inactivation of lassa virus. | in 2006 we had a patient with lassa fever in the university hospital of frankfurt. to insure a short turn-around time from the laboratory, it was necessary to have blood which was not contaminated with viruses. one method of achieving this is by irradiating the blood with high doses of ionising radiation. inactivation of arena viruses requires doses between 12 kgy and 20 kgy, depending on temperature. in this study we investigated if plasma and serum parameters are changed by irradiation with 5 ... | 2009 | 19707804 |
| inhibition of lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1)-antitrypsin variants. | proteolytic processing of the lassa virus envelope glycoprotein precursor gp-c by the host proprotein convertase site 1 protease (s1p) is a prerequisite for the incorporation of the subunits gp-1 and gp-2 into viral particles and, hence, essential for infectivity and virus spread. therefore, we tested in this study the concept of using s1p as a target to block efficient virus replication. | 2009 | 19488405 |
| non-infectious plasmid engineered to simulate multiple viral threat agents. | the aim of this study was to design and construct a non-virulent simulant to replace several pathogenic viruses in the development of detection and identification methods in biodefense. a non-infectious simulant was designed and engineered to include the nucleic acid signature of veev (venezuelan equine encephalitis virus), influenza virus, rift valley fever virus, machupo virus, lassa virus, yellow fever virus, ebola virus, eastern equine encephalitis virus, junin virus, marburg virus, dengue v ... | 2009 | 19442841 |
| characterization of lassa virus cell entry inhibitors: determination of the active enantiomer by asymmetric synthesis. | the comparative characterization of a series of 4-acyl-1,6-dialkylpiperazin-2-ones as potent cell entry inhibitors of the hemorrhagic fever arenavirus lassa (lasv) is disclosed. the resolution and examination of the individual enantiomers of the prototypical lasv cell entry inhibitor 3 (16g8) is reported and the more potent (-)-enantiomer was found to be 15-fold more active than the corresponding (+)-enantiomer. the absolute configuration of (-)-3 was established by asymmetric synthesis of the a ... | 2009 | 19428249 |
| highly specific detection of antibodies to tick-borne encephalitis (tbe) virus in humans using a domain iii antigen and a sensitive immune complex (ic) elisa. | in contrast to most antibodies directed to the envelope glycoprotein of flaviviruses, those to the domain iii (ed3) show serotype-specific reactions. | 2009 | 19409841 |
| fibroblastic reticular cells and their role in viral hemorrhagic fevers. | viral hemorrhagic fevers (vhfs) caused by ebola, marburg and lassa viruses often manifest as multiple organ dysfunction and hemorrhagic shock with high mortality. these viruses target numerous cell types, including monocytes and dendritic cells, which are primary early targets that mediate critical pathogenetic processes. this review focuses on fibroblastic reticular cells (frcs), another prevalent infected cell type that is known as a key regulator of circulatory and immune functions. viral inf ... | 2009 | 19400762 |
| receptor binding and cell entry of old world arenaviruses reveal novel aspects of virus-host interaction. | ten years ago, the first cellular receptor for the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) and the highly pathogenic lassa virus (lasv) was identified as alpha-dystroglycan (alpha-dg), a versatile receptor for proteins of the extracellular matrix (ecm). biochemical analysis of the interaction of alpha-dg with arenaviruses and ecm proteins revealed a strikingly similar mechanism of receptor recognition that critically depends on specific sugar modification on alpha-dg invo ... | 2009 | 19324387 |
| early and strong immune responses are associated with control of viral replication and recovery in lassa virus-infected cynomolgus monkeys. | lassa virus causes a hemorrhagic fever endemic in west africa. the pathogenesis and the immune responses associated with the disease are poorly understood, and no vaccine is available. we followed virological, pathological, and immunological markers associated with fatal and nonfatal lassa virus infection of cynomolgus monkeys. the clinical picture was characterized by fever, weight loss, depression, and acute respiratory syndrome. transient thrombocytopenia and lymphopenia, lymphadenopathy, spl ... | 2009 | 19297492 |
| models for an arenavirus infection in a rodent population: consequences of horizontal, vertical and sexual transmission. | arenaviruses are associated with rodent-transmitted diseases in humans. five arenaviruses are known to cause human illness: lassa virus, junin virus, machupo virus, guanarito virus and sabia virus. in this investigation, we model the spread of machupo virus in its rodent host calomys callosus. machupo virus infection in humans is known as bolivian hemorrhagic fever (bhf) which has a mortality rate of approximately 5-30% [31]. machupo virus is transmitted among rodents through horizontal (direct ... | 2008 | 19278272 |
| risk maps of lassa fever in west africa. | lassa fever is caused by a viral haemorrhagic arenavirus that affects two to three million people in west africa, causing a mortality of between 5,000 and 10,000 each year. the natural reservoir of lassa virus is the multi-mammate rat mastomys natalensis, which lives in houses and surrounding fields. with the aim of gaining more information to control this disease, we here carry out a spatial analysis of lassa fever data from human cases and infected rodent hosts covering the period 1965-2007. i ... | 2009 | 19255625 |
| a fatal case of lassa fever in london, january 2009. | in january 2009, the eleventh [corrected] case of lassa fever imported to the united kingdom was diagnosed in london. risk assessment of 328 healthcare contacts with potential direct exposure to lassa virus - through contact with the case or exposure to bodily fluids - was undertaken. no contacts were assessed to be at high risk of infection and no secondary clinical cases identified. | 2009 | 19215723 |
| sensorineural hearing loss in lassa fever: two case reports. | abstract: | 2009 | 19178735 |
| characterization of lassa virus cell entry and neutralization with lassa virus pseudoparticles. | the cell entry and humoral immune response of the human pathogen lassa virus (lv), a biosafety level 4 (bsl4) old world arenavirus, are not well characterized. lv pseudoparticles (lvpp) are a surrogate model system that has been used to decipher factors and routes involved in lv cell entry under bsl2 conditions. here, we describe lvpp, which are highly infectious, with titers approaching those obtained with pseudoparticles displaying g protein of vesicular stomatitis virus and their the use for ... | 2009 | 19153226 |
| uncoupling gp1 and gp2 expression in the lassa virus glycoprotein complex: implications for gp1 ectodomain shedding. | sera from convalescent lassa fever patients often contains antibodies to lassa virus (lasv) glycoprotein 1 (gp1), and glycoprotein 2 (gp2); immunization of non-human primates with viral vectors expressing the arenaviral glycoprotein complex (gpc) confers full protective immunity against a lethal challenge with lasv. thus, the development of native or quasi native recombinant lasv gp1 and gp2 as soluble, uncoupled proteins will improve current diagnostics, treatment, and prevention of lassa fever ... | 2008 | 19105844 |
| inhibition of lassa and marburg virus production by tetherin. | recently, tetherin has been identified as an effective cellular factor that prevents the release of human immunodeficiency virus type 1. here, we show that the production of virus-like particles induced by viral matrix proteins of lassa virus or marburg virus was markedly inhibited by tetherin and that n-linked glycosylation of tetherin was dispensable for this antiviral activity. our data also suggest that viral matrix proteins or one or more components that originate from host cells are target ... | 2009 | 19091864 |
| analysis of the differential host cell nuclear proteome induced by attenuated and virulent hemorrhagic arenavirus infection. | arenaviruses are important emerging pathogens and include a number of hemorrhagic fever viruses classified as niaid category a priority pathogens and cdc potential biothreat agents. infection of guinea pigs with the new world arenavirus pichindé virus (picv) has been used as a biosafety level 2 model for the lassa virus. despite continuing research, little is known about the molecular basis of pathogenesis, and this has hindered the design of novel antiviral therapeutics. modulation of the host ... | 2009 | 19004951 |
| nmr assignment of the arenaviral protein z from lassa fever virus. | the arenavirus protein z from lassa fever virus was recently found to inhibit mrna translation through direct interaction with eif4e. here, we report the nmr assignment of this ring-containing protein that was determined by triple resonance nmr techniques. | 2008 | 18958179 |
| cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs. | arenaviruses such as lassa virus cause a spectrum of disease in humans ranging from mild febrile illness to lethal haemorrhagic fever. the contributions of innate immunity to protection or pathogenicity are unknown. we compared patterns of expression of cytokines of innate immunity in mild versus severe arenavirus disease using an established guinea pig model based on the macrophage-tropic arenavirus pichinde virus (picv). cytokine transcripts were measured by using real-time rt-pcr in target or ... | 2008 | 18796726 |
| identification of a broad-spectrum arenavirus entry inhibitor. | several arenaviruses, including lassa virus (lasv), are causative agents of hemorrhagic fever, for which effective therapeutic options are lacking. the lasv envelope glycoprotein (gp) gene was used to generate lentiviral pseudotypes to identify small-molecule inhibitors of viral entry. a benzimidazole derivative with potent antiviral activity was identified from a high-throughput screen utilizing this strategy. subsequent lead optimization for antiviral activity identified a modified structure, ... | 2008 | 18715909 |
| safety, immunogenicity, and efficacy of the ml29 reassortant vaccine for lassa fever in small non-human primates. | a single injection of ml29 reassortant vaccine for lassa fever induces low, transient viremia, and low or moderate levels of ml29 replication in tissues of common marmosets depending on the dose of the vaccination. the vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. dna array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ml29 revealed that gene expressio ... | 2008 | 18692539 |
| mutational evidence for a structural model of the lassa virus rna polymerase domain and identification of two residues, gly1394 and asp1395, that are critical for transcription but not replication of the genome. | the rna-dependent rna polymerase (rdrp) of arenaviruses is an integral part of the l protein, a 200-kda multifunctional and multidomain protein. in view of the paucity of structural data, we recently proposed a model for the rdrp domain of arenaviruses based on the folding of rdrps of plus-strand viruses (s. vieth et al., virology 318:153-168, 2004). in the present study, we have chosen a large-scale mutagenesis approach to gain insight into the structure and function of the lassa virus rdrp dom ... | 2008 | 18667512 |
| bacterial-based systems for expression and purification of recombinant lassa virus proteins of immunological relevance. | there is a significant requirement for the development and acquisition of reagents that will facilitate effective diagnosis, treatment, and prevention of lassa fever. in this regard, recombinant lassa virus (lasv) proteins may serve as valuable tools in diverse antiviral applications. bacterial-based systems were engineered for expression and purification of recombinant lasv nucleoprotein (np), glycoprotein 1 (gp1), and glycoprotein 2 (gp2). | 2008 | 18538016 |
| different mechanisms of cell entry by human-pathogenic old world and new world arenaviruses. | the old world arenavirus lassa virus (lasv) is the causative agent of severe viral hemorrhagic fever (vhf) in humans and is the most prevalent human pathogen among arenaviruses. the present study investigated the largely unknown mechanisms of cell entry of lasv, a process know to be mediated solely by the virus envelope glycoprotein (gp). to circumvent biosafety restrictions associated with the use of live lasv, we used reverse genetics to generate a recombinant variant of the prototypic arenavi ... | 2008 | 18508885 |
| unique small molecule entry inhibitors of hemorrhagic fever arenaviruses. | viral hemorrhagic fevers caused by the arenaviruses lassa virus in africa and machupo, guanarito, junin, and sabia virus in south america are among the most devastating emerging human diseases with fatality rates of 15-35% and a limited antiviral therapeutic repertoire available. here we used high throughput screening of synthetic combinatorial small molecule libraries to identify inhibitors of arenavirus infection using pseudotyped virion particles bearing the glycoproteins (gps) of highly path ... | 2008 | 18474596 |
| processing of genome 5' termini as a strategy of negative-strand rna viruses to avoid rig-i-dependent interferon induction. | innate immunity is critically dependent on the rapid production of interferon in response to intruding viruses. the intracellular pathogen recognition receptors rig-i and mda5 are essential for interferon induction by viral rnas containing 5' triphosphates or double-stranded structures, respectively. viruses with a negative-stranded rna genome are an important group of pathogens causing emerging and re-emerging diseases. we investigated the ability of genomic rnas from substantial representative ... | 2008 | 18446221 |
| human pathogenic arenaviruses. | 2008 | 18300312 | |
| new opportunities for field research on the pathogenesis and treatment of lassa fever. | unlike many viral hemorrhagic fevers (vhfs), lassa fever (lf) is not a rare disease that emerges only as sporadic cases or in outbreak form. although surveillance is inadequate to determine the true incidence, up to 300,000 infections and 5000 deaths from lf are estimated to occur yearly. the highest incidence is in the "mano river union (mru) countries" of sierra leone, liberia, and guinea. although civil unrest in this region over the past two decades has impeded capacity building and research ... | 2008 | 18241935 |
| reproductive characteristics of mastomys natalensis and lassa virus prevalence in guinea, west africa. | we recently reported increased prevalence of lassa virus (lasv) infection in mastomys natalensis during the rainy season in guinea, west africa. here, the association of lasv prevalence with fecundity, fertility, and the age structure of the rodent population was analyzed using data from the previous study. the animals reproduced throughout the year, but highest fecundity was observed during the rainy season. accordingly, the rodent population was aged at the beginning and young at the end of th ... | 2008 | 18237265 |
| [important issues of biological safety]. | the problem of biological security raises alarm due to the real growth of biological threats. biological security includes a wide scope of problems, the solution of which becomes a part of national security as a necessary condition for the constant development of the country. a number of pathogens, such as human immunodeficiency virus, exotic ebola and lassa viruses causing hemorrhagic fever,rotaviruses causing acute intestinal diseases, etc. were first discovered in the last century. terrorist ... | 2007 | 18225506 |
| cell entry by human pathogenic arenaviruses. | the arenaviruses lassa virus (lasv) in africa and machupo (macv), guanarito (gtov) and junin viruses (junv) in south america cause severe haemorrhagic fevers in humans with fatality rates of 15-35%. the present review focuses on the first steps of infection with human pathogenic arenaviruses, the interaction with their cellular receptor molecules and subsequent entry into the host cell. while similarities exist in genomic organization, structure and clinical disease caused by pathogenic old worl ... | 2008 | 18182084 |
| strain-specific antibody response to lassa virus in the local population of west africa. | lassa virus (lav) isolates obtained from sierra leone, ivory coast and nigeria show a high degree of amino acid difference [gunther s, weisner b, roth a, grewing t, asper m, drosten c, et al. lassa fever encephalopathy: lassa virus in cerebrospinal fluid but not in serum. j infect dis 2001;184:345-9]. therefore, three lav strains from sierra leone, ivory coast and nigeria were used as antigens to study the anti-lav antibody response in 960 serum samples obtained from different regions of west af ... | 2008 | 18164653 |
| genistein treatment of cells inhibits arenavirus infection. | arenaviridae is a family of enveloped viruses some of which are capable of causing hemorrhagic fever syndromes in humans. in this report, we demonstrate that treatment of host cells with the tyrosine kinase inhibitor genistein inhibits infection of cells with the new world arenavirus pichindé (picv). the greatest degree of inhibition was observed in pre-treated target cells, but modest inhibition of infection was also seen when drug was added to cultures up to 48h after infection. we show that p ... | 2008 | 17961732 |
| genome-wide detection and characterization of positive selection in human populations. | with the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. here we report an analysis of over 3 million polymorphisms from the international hapmap project phase 2 (hapmap2). we used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover allel ... | 2007 | 17943131 |
| rt-pcr assay for detection of lassa virus and related old world arenaviruses targeting the l gene. | this study describes an rt-pcr assay targeting the l rna segment of arenaviruses. conserved regions were identified in the polymerase domain of the l gene on the basis of published sequences for lassa virus, lymphocytic choriomeningitis virus (lcmv), pichinde virus and tacaribe virus, as well as 15 novel sequences for lassa virus, lcmv, ippy virus, mobala virus and mopeia virus determined in this study. using these regions as target sites, a pcr assay for detection of all known old world arenavi ... | 2007 | 17905372 |
| arenavirus entry occurs through a cholesterol-dependent, non-caveolar, clathrin-mediated endocytic mechanism. | arenaviruses are important causes of viral hemorrhagic fevers in humans. arenavirus infection of cells occurs via a ph-dependent endocytic route, but detailed studies of entry pathways have not been done. we investigated the role of cell membrane cholesterol, caveolae, and clathrin coated pits in infection by lassa virus (lasv), which utilizes alpha-dystroglycan (alpha-dg) as a receptor, and pichindé virus (picv), which does not. depletion of cellular cholesterol by treatment with methyl betacyc ... | 2007 | 17698159 |
| development of recombinant nucleoprotein-based diagnostic systems for lassa fever. | diagnostic systems for lassa fever (lf), a viral hemorrhagic fever caused by lassa virus (lasv), such as enzyme immunoassays for the detection of lasv antibodies and lasv antigens, were developed using the recombinant nucleoprotein (rnp) of lasv (lasv-rnp). the lasv-rnp was expressed in a recombinant baculovirus system. lasv-rnp was used as an antigen in the detection of lasv-antibodies and as an immunogen for the production of monoclonal antibodies. the lasv-rnp was also expressed in hela cells ... | 2007 | 17634509 |
| lassa virus-infected rodents in refugee camps in guinea: a looming threat to public health in a politically unstable region. | rodent-borne and other communicable diseases are of particular concern to vulnerable populations in complex humanitarian emergencies. we assessed the risk of lassa fever to refugees and humanitarian aid workers in the forest region of guinea by trapping rodents and testing them for the presence of lassa virus infection. our study provides a point prevalence of lassa virus-infected rodents in various refugee camps in guinea, suggesting that the risk of disease may be highest in camps further sout ... | 2007 | 17627434 |
| fluctuation of abundance and lassa virus prevalence in mastomys natalensis in guinea, west africa. | based on empiric surveillance data, the incidence of human lassa fever (lf) cases in guinea and other west african countries has been reported to increase during the dry season compared to the rainy season. to investigate possible links with the ecology of the rodent reservoir of the virus, we conducted a 2-year longitudinal survey of mastomys natalensis in a region of high human lassa virus (lasv) seropositivity in guinea. standardized rodent trapping with similar trapping efforts between seaso ... | 2007 | 17627428 |
| amino acids from both n-terminal hydrophobic regions of the lassa virus envelope glycoprotein gp-2 are critical for ph-dependent membrane fusion and infectivity. | lassa virus glycoprotein 2 (lasv gp-2) belongs to the class i fusion protein family. its n terminus contains two stretches of highly conserved hydrophobic amino acids (residues 260-266 and 276-298) that have been proposed as n-terminal or internal fusion peptide segments (n-fps, i-fps) by analogy with similar sequences of other viral glycoproteins or based on experimental data obtained with synthetic peptides, respectively. by using a ph-dependent, recombinant lasv glycoprotein mediated cell-cel ... | 2007 | 17622638 |
| arenavirus z-glycoprotein association requires z myristoylation but not functional ring or late domains. | generation of infectious arenavirus-like particles requires the virus ring finger z protein and surface glycoprotein precursor (gpc) and the correct processing of gpc into gp1, gp2, and a stable signal peptide (ssp). z is the driving force of arenavirus budding, whereas the gp complex (gpc), consisting of hetero-oligomers of ssp, gp1, and gp2, forms the viral envelope spikes that mediate receptor recognition and cell entry. based on the roles played by z and gp in the arenavirus life cycle, we h ... | 2007 | 17581989 |
| early blood profiles of virus infection in a monkey model for lassa fever. | acute arenavirus disease in primates, like lassa hemorrhagic fever in humans, begins with flu-like symptoms and leads to death approximately 2 weeks after infection. our goal was to identify molecular changes in blood that are related to disease progression. rhesus macaques (macaca mulatta) infected intravenously with a lethal dose of lymphocytic choriomeningitis virus (lcmv) provide a model for lassa virus infection of humans. blood samples taken before and during the course of infection were u ... | 2007 | 17522210 |
| [lassa fever]. | 2007 | 17494143 | |
| analysis of gene expression in lassa virus-infected huh-7 cells. | the pathogenesis of lassa fever is poorly understood. as the liver is a major target organ of lassa virus, gene expression in lassa virus-infected huh-7 cells, a differentiated human hepatoma cell line, was studied. cellular mrna levels were measured at the late phase of acute infection, when virtually all cells expressed large amounts of nucleoprotein, and virus rna concentration had reached>10(8) copies (ml supernatant)-1. two types of transcription array were used: cdna-based macroarrays with ... | 2007 | 17412988 |
| lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues. | lassa virus causes thousands of deaths annually in western africa and is considered a potential biological weapon. in an attempt to develop a small nonhuman primate model of lassa fever, common marmosets were subcutaneously inoculated with lassa virus strain josiah. this inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human lassa infection: fever, weight loss, high viremia and viral rna load in tissues, elevated liver enzymes, and seve ... | 2007 | 17409137 |
| lassa fever in west african sub-region: an overview. | lassa fever is an acute viral zoonotic illness caused by lassa virus, an arenavirus known to be responsible for a severe haemorrhagic fever characterised by fever, muscle aches, sore throat, nausea, vomiting and, chest and abdominal pain. the virus exhibits persistent, asymptomatic infection with profuse urinary virus excretion in the ubiquitous rodent vector, mastomys natalensis. lassa fever is endemic in west africa and has been reported from sierra leone, guinea, liberia, and nigeria. some st ... | 2007 | 17378212 |
| broad-spectrum antiviral activity of small interfering rna targeting the conserved rna termini of lassa virus. | small interfering rnas targeting the conserved rna termini upstream of np and l gene were found to reduce reporter gene expression from lassa virus replicon and lassa virus mrna expression construct and to inhibit replication of different lassa virus strains, lymphocytic choriomeningitis virus, and mopeia virus in cell culture. | 2007 | 17371814 |
| old world and clade c new world arenaviruses mimic the molecular mechanism of receptor recognition used by alpha-dystroglycan's host-derived ligands. | alpha-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, alpha-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 i ... | 2007 | 17360738 |
| a ml29 reassortant virus protects guinea pigs against a distantly related nigerian strain of lassa virus and can provide sterilizing immunity. | lassa virus (lasv) is responsible for the deaths of thousands of people in west africa annually. genetic diversity among lasv strains is the highest among the arenaviridae and represents a great challenge for vaccine development. guinea pigs vaccinated with a ml29 reassortant vaccine experienced sterilizing immunity and complete protection when challenged on day 30 either with homologous virus or with the distantly related nigerian isolate. simultaneous vaccination-challenge or challenge on day ... | 2007 | 17360080 |
| mastomys natalensis and lassa fever, west africa. | pcr screening of 1,482 murid rodents from 13 genera caught in 18 different localities of guinea, west africa, showed lassa virus infection only in molecularly typed mastomys natalensis. distribution of this rodent and relative abundance compared with m. erythroleucus correlates geographically with lassa virus seroprevalence in humans. | 2006 | 17326956 |
| thioaptamer decoy targeting of ap-1 proteins influences cytokine expression and the outcome of arenavirus infections. | viral haemorrhagic fever (vhf) is caused by a number of viruses, including arenaviruses. the pathogenesis is believed to involve dysregulation of cytokine production. the arenaviruses lassa virus and pichinde virus have a tropism for macrophages and other reticuloendothelial cells and both appear to suppress the normal macrophage response to virus infection. a decoy thioaptamer, xby-s2, was developed and was found to bind to ap-1 transcription factor proteins. the p388d1 macrophage-like cell lin ... | 2007 | 17325372 |
| transferrin receptor 1 is a cellular receptor for new world haemorrhagic fever arenaviruses. | at least five arenaviruses cause viral haemorrhagic fevers in humans. lassa virus, an old world arenavirus, uses the cellular receptor alpha-dystroglycan to infect cells. machupo, guanarito, junin and sabia viruses are new world haemorrhagic fever viruses that do not use alpha-dystroglycan. here we show a specific, high-affinity association between transferrin receptor 1 (tfr1) and the entry glycoprotein (gp) of machupo virus. expression of human tfr1, but not human transferrin receptor 2, in ha ... | 2007 | 17287727 |
| [detection of anti-lassa antibodies in the western forest area of the ivory coast]. | lassa fever is an african viral hemorrhagic fever (vhf) known to be endemic in a number of west african countries including nigeria, sierra leone, liberia and guinea. despite having common borders with liberia and guinea, côte d'ivoire has never reported any cases of lassa fever. in march 2000, as part of a research project on vhf--mainly yellow fever, lassa fever and ebola fever--in guinea and cote d'ivoire, an exploratory survey was conducted to assess knowledge about vhf and immunological sta ... | 2006 | 17201291 |
| molecular characterization of a reassortant virus derived from lassa and mopeia viruses. | in this article we describe two new complete genomic sequences of old world arenaviruses: the mopeia (mop) virus and the reassortant mop/las virus, clone 29, or ml29. this reassortant has the large (l) rna from mop virus and the small (s) rna from lassa (las) virus, josiah strain. recent studies showed that the ml29 virus is not pathogenic for mice, guinea pigs, or macaques, can completely protect guinea pigs from lassa virus, and elicit vigorous cell-mediated immunity in immunized monkeys (luka ... | 2007 | 17143722 |
| [hemorrhagic (marburg, ebola, lassa, and bolivian) fevers: epidemiology, clinical pictures, and treatment]. | the evaluation of the biological and epidemiological properties of ebola, marburg, lassa, and machupo viruses suggests that they are of social importance for health care authorities. the studies have created prerequisites to the development of reliable biosafety means against these pathogens. particular emphasis is laid on the methods for infection diagnosis and on the studies to design specific protective agents--immunoglobulins and inactivated vaccines. | 2006 | 17087059 |
| the role of myristoylation in the membrane association of the lassa virus matrix protein z. | the z protein is the matrix protein of arenaviruses and has been identified as the main driving force for budding. both lcmv and lassa virus z proteins bud from cells in the absence of other viral proteins as enveloped virus-like particles. z accumulates near the inner surface of the plasma membrane where budding takes place. furthermore, biochemical data have shown that z is strongly membrane associated. the primary sequence of z lacks a typical transmembrane domain and until now it is not unde ... | 2006 | 17083745 |
| mutational analysis of the lassa virus promoter. | the promoter sequences directing viral gene expression and genome replication of arenaviruses reside within the 3' and 5' termini of each rna segment. the terminal 19 nucleotides at both ends are highly conserved among all arenavirus species and are almost completely complementary to each other. this study aimed at characterizing the lassa virus promoter in detail. the relevance of each position in the promoter was studied by site-directed mutagenesis using the lassa virus minireplicon system. t ... | 2006 | 17005649 |
| reverse elisa for igg and igm antibodies to detect lassa virus infections in africa. | anti-lassa antibodies are detected by indirect immunofluorescence assay (ifa) or by enzyme-immunoassay (elisa). both methods have problems to detect low amounts of specific antibodies. | 2006 | 16996789 |
| recombinant expression, purification, and kinetic and inhibitor characterisation of human site-1-protease. | human site-1-protease (s1p, merops s08.8063), also widely known as subtilisin/kexin isozyme 1 (ski-1), is a membrane bound subtilisin-related serine protease, that belongs to a group of nine mammalian proprotein convertases. among these proteases, s1p displays unique substrate specificity, by showing preferred cleavage after non-basic amino acids. s1p plays a key role in a proteolytic pathway that controls the cholesterol content of membranes, cells and blood. s1p also participates in the activa ... | 2007 | 16973377 |
| identification of protective lassa virus epitopes that are restricted by hla-a2. | recovery from lassa virus (lasv) infection usually precedes the appearance of neutralizing antibodies, indicating that cellular immunity plays a primary role in viral clearance. to date, the role of lasv-specific cd8(+) t cells has not been evaluated in humans. to facilitate such studies, we utilized a predictive algorithm to identify candidate hla-a2 supertype epitopes from the lasv nucleoprotein and glycoprotein precursor (gpc) genes. we identified three peptides (gpc(42-50), glvglvtfl; gpc(60 ... | 2006 | 16912286 |
| viral haemorrhagic fevers caused by lassa, ebola and marburg viruses. | 2006 | 16802617 | |
| receptor use by pathogenic arenaviruses. | the arenavirus family contains several important human pathogens including lassa fever virus (lasv), lymphocytic choriomeningitis virus (lcmv) and the new world clade b viruses junin (junv) and machupo (macv). previously, alpha-dystroglycan (alpha-dg) was identified as a receptor recognized by lasv and certain strains of lcmv. however, other studies have suggested that alpha-dg is probably not used by the clade b viruses, and the receptor(s) for these pathogens is currently unknown. using pseudo ... | 2006 | 16797051 |
| the proprotein convertase ski-1/s1p. in vitro analysis of lassa virus glycoprotein-derived substrates and ex vivo validation of irreversible peptide inhibitors. | herein we designed, synthesized, tested, and validated fluorogenic methylcoumarinamide (mca) and chloromethylketone-peptides spanning the lassa virus gpc cleavage site as substrates and inhibitors for the proprotein convertase ski-1/s1p. the 7-mer mca (yisrrll-mca) and 8-mer mca (iyisrrll-mca) are very efficiently cleaved with respect to both the 6-mer mca (isrrll-mca) and point mutated fluorogenic analogues, except for the 7-mer mutant y253f. the importance of the p7 phenylic residue was confir ... | 2006 | 16790437 |
| the role of single n-glycans in proteolytic processing and cell surface transport of the lassa virus glycoprotein gp-c. | lassa virus glycoprotein is synthesised as a precursor (pregp-c) into the lumen of the endoplasmic reticulum. after cotranslational cleavage of the signal peptide, the immature gp-c is posttranslationally processed into the n-terminal subunit gp-1 and the c-terminal subunit gp-2 by the host cell subtilase ski-1/s1p. the glycoprotein precursor contains eleven potential n-glycosylation sites. in this report, we investigated the effect of each n-glycan on proteolytic cleavage and cell surface trans ... | 2006 | 16737539 |
| historical lassa fever reports and 30-year clinical update. | five cases of lassa fever have been imported from west africa to the united states since 1969. we report symptoms of the patient with the second imported case and the symptoms and long-term follow-up on the patient with the third case. vertigo in this patient has persisted for 30 years. | 2006 | 16704848 |
| role of interferons in the control of lassa virus replication in human dendritic cells and macrophages. | lassa fever is a hemorrhagic fever caused by lassa virus (lv), which primarily targets human dendritic cells (dc) and macrophages (mp). massive numbers of viral particles are released with no effect on the viability, activation or maturation of these cells. lv does not inhibit the activation of cells induced by scd40l or lps. we report here the consequences of exogenous activation of lv-infected human dc and mp for viral replication. the activation of cells with lipopolysaccharide or exogenous p ... | 2006 | 16621649 |
| narrowed tcr repertoire and viral escape as a consequence of heterologous immunity. | why some virus-specific cd8 tcr repertoires are diverse and others restricted or "oligoclonal" has been unknown. we show here that oligoclonality and extreme clonal dominance can be a consequence of t cell cross-reactivity. lymphocytic choriomeningitis virus (lcmv) and pichinde virus (pv) encode np(205-212) epitopes that induce different but highly cross-reactive diverse tcr repertoires. homologous viral challenge of immune mice only slightly skewed the repertoire and enriched for predictable tc ... | 2006 | 16614754 |
| cellular factors required for lassa virus budding. | it is known that lassa virus z protein is sufficient for the release of virus-like particles (vlps) and that it has two l domains, ptap and pppy, in its c terminus. however, little is known about the cellular factor for lassa virus budding. we examined which cellular factors are used in lassa virus z budding. we demonstrated that lassa z protein efficiently produces vlps and uses cellular factors, vps4a, vps4b, and tsg101, in budding, suggesting that lassa virus budding uses the multivesicular b ... | 2006 | 16571837 |
| [the mammals of guinea as reservoirs and carriers of arboviruses]. | a great body of data on the fauna and ecology of wild mammals and their participation in the circulation of arboviruses were collected when the ecology of the latter of the republic of guinea was studied in 1978 to 1989. a hundred and eighteen species belonging to 10 orders were identified. over 2,000 biological specimens were virologically and serologically examined. six arboviruses were isolated. these included dugbe virus (from the hussar monkey cercopithecus (erythrocebus patas) and 5 viruse ... | 2006 | 16562748 |
| scv-07 (sciclone pharmaceuticals/verta). | sciclone pharmaceuticals and verta are developing scv-07, the lead in a series of immnunostimulants from verta, for the potential treatment of tuberculosis and hepatitis c virus infection. phase ii clinical trials of the compound are ongoing. | 2006 | 16499289 |
| phylogeny and evolution of old world arenaviruses. | the intention of this study was to investigate the genomics, phylogeny and evolution of the old world arenaviruses based on sequence data representing the four viral genes. to achieve this aim, we sequenced the complete s and l rna segments of ippy virus (ippyv), mobala virus (mobv) and mopeia virus (mopv). full-length sequences of the np, gpc, z and l genes were used to reconstruct phylogenetic relationships and to compare resulting tree topologies. each of the five old world arenavirus species ... | 2006 | 16494913 |
| a clinical guide to viral haemorrhagic fevers: ebola, marburg and lassa. | the viral haemorrhagic fevers are a group of diseases that share many clinical features. ebola, marburg and lassa are diseases that cause a relatively small number of deaths globally, but pose special risks to medical staff due to the ease of transmission, and can have a profound impact to the communities they affect. this article gives a brief overview of diseases caused by the ebola, marburg and lassa viruses. it gives some practical advice to the clinician on the diagnosis and management of t ... | 2006 | 16483416 |
| a recombinant yellow fever 17d vaccine expressing lassa virus glycoproteins. | the yellow fever vaccine 17d (yfv17d) has been used as a vector for the lassa virus glycoprotein precursor (lasv-gpc) resulting in construction of yfv17d/lasv-gpc recombinant virus. the virus was replication-competent and processed the lasv-gpc in cell cultures. the recombinant replicated poorly in guinea pigs but still elicited specific antibodies against lasv and yfv17d antigens. a single subcutaneous injection of the recombinant vaccine protected strain 13 guinea pigs against fatal lassa feve ... | 2006 | 16412488 |
| [clinical aspects of viral hemorrhagic fever]. | viral hemorrhagic fever (vhf) is defined as virus infections that usually cause pyrexia and hemorrhagic symptoms with multiple organ failure. vhf includes following viral infections: ebola hemorrhagic fever (ehf), marburg hemorrhagic fever (mhf), crimean-congo hemorrhagic fever (cchf) and lassa fever. in particular, the causative agents of ehf, mhf, cchf, and lassa fever are ebola, marburg, cchf, lassa viruses, respectively, and regarded as biosafety level-4 pathogens because of their high virul ... | 2005 | 16363689 |
| lassa fever, nigeria, 2003 and 2004. | 2005 | 16355508 | |
| taking down goliaths: new vaccines may spell the end for ebola, marburg and lassa virus infections. | 2005 | 16323509 | |
| a live attenuated vaccine for lassa fever made by reassortment of lassa and mopeia viruses. | lassa virus (lasv) and mopeia virus (mopv) are closely related old world arenaviruses that can exchange genomic segments (reassort) during coinfection. clone ml29, selected from a library of mopv/lasv (mop/las) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of lasv and the rna polymerase and zinc-binding protein of mopv. replication of ml29 was attenuated in guinea pigs and nonhuman primates. in murine adoptive-transfer experiments, as little as 150 pfu of ml29 induced ... | 2005 | 16254329 |
| lassa fever virus peptides predicted by computational analysis induce epitope-specific cytotoxic-t-lymphocyte responses in hla-a2.1 transgenic mice. | lassa fever is a hemorrhagic disease caused by lassa fever virus (lv). although the precise host defense mechanism(s) that affords protection against lv is not completely understood, cellular immunity mediated by cytotoxic t lymphocytes (ctls) plays a pivotal role in controlling viral replication and lv infection. to date, there have been no reports mapping major histocompatibility complex (mhc) class i-binding ctl epitopes for lv. using computer-assisted algorithms, we identified five hla-a2.1- ... | 2005 | 16210487 |
| quality assurance for the diagnostics of viral diseases to enhance the emergency preparedness in europe. | the threat posed by emerging and re-emerging communicable diseases and, more recently, by the intentional release of infectious agents in a susceptible population, has been receiving considerable attention at the national and international levels. public health efforts to strengthen disease detection, surveillance and control have been intensified. however, clinicians and clinical microbiology laboratories play an important role in the early detection of disease, the identification of the putati ... | 2005 | 16077216 |
| some tolerance for fur--animal studies in plos medicine. | 2005 | 15971961 | |
| development of a new vaccine for the prevention of lassa fever. | recent importation of lassa fever into germany, the netherlands, the united kingdom, and the united states by travelers on commercial airlines from africa underscores the public health challenge of emerging viruses. currently, there are no licensed vaccines for lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge. | 2005 | 15971954 |
| 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 als ... | 2005 | 15964478 |
| characterization of the interaction of lassa fever virus with its cellular receptor alpha-dystroglycan. | the cellular receptor for the old world arenaviruses lassa fever virus (lfv) and lymphocytic choriomeningitis virus (lcmv) has recently been identified as alpha-dystroglycan (alpha-dg), a cell surface receptor that provides a molecular link between the extracellular matrix and the actin-based cytoskeleton. in the present study, we show that lfv binds to alpha-dg with high affinity in the low-nanomolar range. recombinant vesicular stomatitis virus pseudotyped with lfv glycoprotein (gp) adopted th ... | 2005 | 15857984 |
| evaluating the immunogenicity and protective efficacy of a dna vaccine encoding lassa virus nucleoprotein. | several viruses in the arenavirus genus of the family arenaviridae cause severe, often fatal, hemorrhagic fever. one such virus, lassa virus (lv), is a frequent cause of disease in africa, and survivors often are left with substantial neurological impairment. the feasibility of protective immunization against lv infection, and the associated disease, has been demonstrated in animal models, using recombinant vaccinia viruses to deliver lassa proteins. circumstantial evidence implicates cellular i ... | 2005 | 15823608 |
| zidampidine, an aryl phosphate derivative of azt: in vivo pharmacokinetics, metabolism, toxicity, and anti-viral efficacy against hemorrhagic fever caused by lassa virus. | the pharmacokinetics, metabolism, and toxicity of zidampidine, an aryl phosphate derivative of azt, 3'-azidothymidine-5'-[p-bromophenyl methoxyalaninyl phosphate] were investigated in cd-1 mice. following iv injection, zidampidine was rapidly converted to its metabolites ala-azt-mp and azt. zidampidine was not toxic to mice at doses up to 250mg/kg. we next examined the therapeutic effect of zidampidine in cba mice challenged with intracerebral injections of the josiah strain of lassa virus. mice ... | 2005 | 15809163 |
| sonja buckley. | 2005 | 15786567 |