Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| [lassa fever]. | 2007 | 17494143 | |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| [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 |
| 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 |
| 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 |
| human pathogenic arenaviruses. | 2008 | 18300312 | |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| sensorineural hearing loss in lassa fever: two case reports. | abstract: | 2009 | 19178735 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| lassa fever, nigeria, 2005-2008. | 2010 | 20507773 | |
| laboratory diagnosis of lassa fever, liberia. | 2010 | 20507774 | |
| the flexible c-terminal arm of the lassa arenavirus z-protein mediates interactions with multiple binding partners. | the arenavirus genome encodes for a z-protein, which contains a ring domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mrna translation, and apoptosis of infected cells. using homology models of the z-protein from lassa strain arenavirus, replica exchange molecular dynamics (md) was u ... | 2010 | 20544962 |
| innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes. | arenaviruses such as lassa virus (lasv) cause significant morbidity and mortality in endemic areas. using a glycoprotein (gp) exchange strategy, we have recently developed live-attenuated arenavirus vaccine prototypes (rlcmv/vsvg) based on lymphocytic choriomeningitis virus (lcmv), a close relative of lasv. rlcmv/vsvg induced long-term cd8(+) t cell immunity against wild-type virus challenge and exhibited a stably attenuated phenotype in vivo. here we elucidated the innate and adaptive immune re ... | 2010 | 20584765 |
| detection of lassa virus, mali. | to determine whether lassa virus was circulating in southern mali, we tested samples from small mammals from 3 villages, including soromba, where in 2009 a british citizen probably contracted a lethal lassa virus infection. we report the isolation and genetic characterization of lassa virus from an area previously unknown for lassa fever. | 2010 | 20587185 |
| fibroblastic reticular cell infection by hemorrhagic fever viruses. | viral hemorrhagic fevers (vhfs) often cause high mortality with high infectivity, multiorgan failure, shock and hemorrhagic diathesis. fibroblastic reticular cells (frcs) within secondary lymphoid organs provide a supporting scaffold to t-lymphocyte areas. these cells regulate the movement of various immune cells and soluble molecules that promote t-lymphocyte homeostasis. we previously reported ebola virus infection of frcs, but ascribed little significance to this finding. here, we studied inf ... | 2009 | 20635940 |
| a multivalent vaccination strategy for the prevention of old world arenavirus infection in humans. | arenaviruses cause severe human disease ranging from aseptic meningitis following lymphocytic choriomeningitis virus (lcmv) infection to hemorrhagic fever syndromes following infection with guanarito virus (gtov), junin virus (junv), lassa virus (lasv), machupo virus (macv), sabia virus (sabv), or whitewater arroyo virus (wwav). cellular immunity, chiefly the cd8(+) t-cell response, plays a critical role in providing protective immunity following infection with the old world arenaviruses lasv an ... | 2010 | 20668086 |
| rodent host cell/lassa virus interactions: evolution and expression of α-dystroglycan, large-1 and large-2 genes, with special emphasis on the mastomys genus. | arenaviruses are usually rodent-borne viruses that constitute a major threat for human health. among them, lassa fever virus (lfv) occurs in western africa where it infects hundreds of thousands of people annually. according to the most recent surveys, lfv is hosted by one of the multimammate rats, mastomys natalensis, but has never been detected in its sibling and sometimes sympatric species mastomys erythroleucus. this pattern suggests that intrinsic, i.e. genetic properties underlie such a dr ... | 2010 | 20674789 |
| viral haemorrhagic fevers imported into non-endemic countries: risk assessment and management. | viral haemorrhagic fevers (vhfs) are severe infections capable of causing haemorrhagic disease and fatal multi-organ failure. crimean-congo, marburg, ebola and lassa viruses cause both sporadic cases and large epidemics over wide endemic areas. | 2010 | 20682627 |
| infectious lassa virus, but not filoviruses, is restricted by bst-2/tetherin. | bone marrow stromal antigen 2 (bst-2/tetherin) is a cellular membrane protein that inhibits the release of hiv-1. we show for the first time, using infectious viruses, that bst-2 also inhibits egress of arenaviruses but has no effect on filovirus replication and spread. specifically, infectious lassa virus (lasv) release significantly decreased or increased in human cells in which bst-2 was either stably expressed or knocked down, respectively. in contrast, replication and spread of infectious z ... | 2010 | 20686043 |
| proteomic analysis of pichindé virus infection identifies differential expression of prothymosin-alpha. | the arenaviruses include a number of important pathogens including lassa virus and junin virus. presently, the only treatment is supportive care and the antiviral ribavirin. in the event of an epidemic, patient triage may be required to more effectively manage resources; the development of prognostic biomarker signatures, correlating with disease severity, would allow rational triage. using a pair of arenaviruses, which cause mild or severe disease, we analyzed extracts from infected cells using ... | 2010 | 20706531 |
| 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 |
| persistence in darkness of virulent alphaviruses, ebola virus, and lassa virus deposited on solid surfaces. | ebola, lassa, venezuelan equine encephalitis, and sindbis viruses were dried onto solid surfaces, incubated for various time periods under controlled conditions of temperature and relative humidity, and quantitatively eluted from surfaces, and viral titers in the recovered samples were determined. the viral inactivation kinetics that were obtained indicated that viral resistance to natural inactivation in the dark follows (in decreasing order of stability) alphavirus > lassa virus > ebola virus. ... | 2010 | 20842393 |
| imported lassa fever, pennsylvania, usa, 2010. | we report a case of lassa fever in a us traveler who visited rural liberia, became ill while in country, sought medical care upon return to the united states, and subsequently had his illness laboratory confirmed. the patient recovered with supportive therapy. no secondary cases occurred. | 2010 | 20875288 |
| maturation cleavage within the ectodomain of lassa virus glycoprotein relies on stabilization by the cytoplasmic tail. | the lassa virus glycoprotein consists of an ectodomain, a transmembrane anchor, and a cytoplasmic domain. it is synthesized as an inactive precursor and cleaved within the ectodomain to yield the mature form. here, we show that this maturation cleavage can be abolished by mutation of single conserved amino acids within the cytoplasmic domain at the carboxy-terminus of the glycoprotein. moreover, substitutions and deletions of multiple amino acids result in destabilization of the glycoprotein oli ... | 2010 | 20875414 |
| lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for lassa hemorrhagic fever. | lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of western and central african nations where it is endemic. treatment of acute lassa fever infections has successfully utilized intravenous administration of ribavirin, a nucleotide analogue drug, but this is not an approved use; efficacy of oral administration has not been demonstrated. to date, several potential new vaccine platforms have been explored, but none have progressed t ... | 2010 | 20961433 |
| domain structure of lassa virus l protein. | the 200-kda l protein of arenaviruses plays a central role in viral genome replication and transcription. this study aimed at providing evidence for the domain structure of l protein by combining bioinformatics with a stepwise mutagenesis approach using the lassa virus minireplicon system. potential interdomain linkers were predicted using various algorithms. the prediction was challenged by insertion of flexible sequences into the predicted linkers. insertion of 5 or 10 amino acid residues was ... | 2010 | 20980514 |
| reverse genetics generation of chimeric infectious junin/lassa virus is dependent on interaction of homologous glycoprotein stable signal peptide and g2 cytoplasmic domains. | the arenaviridae are a diverse and globally distributed collection of viruses that are maintained primarily by rodent reservoirs. junin virus (junv) and lassa virus (lasv) can both cause significant outbreaks of severe and often fatal human disease throughout their respective areas of endemicity. in an effort to improve upon the existing live attenuated junv candid1 vaccine, we generated a genetically homogenous stock of this virus from cdna copies of the virus s and l segments by using a revers ... | 2010 | 20980515 |
| review of the literature and proposed guidelines for the use of oral ribavirin as postexposure prophylaxis for lassa fever. | lassa fever is an acute viral hemorrhagic illness; the virus is endemic in west africa and also of concern with regard to bioterrorism. transmission of lassa virus between humans may occur through direct contact with infected blood or bodily secretions. oral administration of the antiviral drug ribavirin is often considered for postexposure prophylaxis, but no systematically collected data or uniform guidelines exist for this indication. furthermore, the relatively low secondary attack rates for ... | 2010 | 21058912 |
| shedding of soluble glycoprotein 1 detected during acute lassa virus infection in human subjects. | abstract: background: lassa hemorrhagic fever (lhf) is a neglected tropical disease with significant impact on the health care system, society, and economy of western and central african nations where it is endemic. with a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. previous work by our group identified a soluble isoform of the lassa virus (las ... | 2010 | 21062490 |
| antiviral activity of a small-molecule inhibitor of arenavirus glycoprotein processing by the cellular site 1 protease. | arenaviruses merit interest as clinically important human pathogens and include several causative agents, chiefly lassa virus (lasv), of hemorrhagic fever disease in humans. there are no licensed lasv vaccines, and current antiarenavirus therapy is limited to the use of ribavirin, which is only partially effective and is associated with significant side effects. the arenavirus glycoprotein (gp) precursor gpc is processed by the cellular site 1 protease (s1p) to generate the peripheral virion att ... | 2010 | 21068251 |
| cap binding and immune evasion revealed by lassa nucleoprotein structure. | lassa virus, the causative agent of lassa fever, causes thousands of deaths annually and is a biological threat agent, for which there is no vaccine and limited therapy. the nucleoprotein (np) of lassa virus has essential roles in viral rna synthesis and immune suppression, the molecular mechanisms of which are poorly understood. here we report the crystal structure of lassa virus np at 1.80 å resolution, which reveals amino (n)- and carboxy (c)-terminal domains with structures unlike any of the ... | 2010 | 21085117 |
| sensitivity to ultraviolet radiation of lassa, vaccinia, and ebola viruses dried on surfaces. | germicidal uv (also known as uvc) provides a means to decontaminate infected environments as well as a measure of viral sensitivity to sunlight. the present study determined uvc inactivation slopes (and derived d(37) values) of viruses dried onto nonporous (glass) surfaces. the data obtained indicate that the uv resistance of lassa virus is higher than that of ebola virus. the uv sensitivity of vaccinia virus (a surrogate for variola virus) appeared intermediate between that of the two virulent ... | 2010 | 21104283 |
| use of single-cycle infectious lymphocytic choriomeningitis virus to study hemorrhagic fever arenaviruses. | several arenaviruses, chiefly lassa virus (lasv) and junin virus in west africa and argentina, respectively, cause hemorrhagic fever (hf) disease in humans that is associated with high morbidity and significant mortality. the investigation of antiviral strategies to combat hf arenaviruses is hampered by the requirement of biosafety level 4 (bsl-4) facilities to work with these viruses. these biosafety hurdles could be overcome by the use of recombinant single-cycle infectious arenaviruses. to ex ... | 2010 | 21123370 |
| presence of mopeia virus, an african arenavirus, related to biotope and individual rodent host characteristics: implications for virus transmission. | abstract the east african mopeia virus (mopv) is an arenavirus closely related to the highly pathogenic west african lassa virus, even sharing the same reservoir rodent host mastomys natalensis. because mopv is not known to cause human disease, it offers a unique alternative for studying lassa virus transmission. we investigated how habitat, population density, and host characteristics are related to mopv occurrence in m. natalensis populations in morogoro, tanzania. in 3 contrasting habitats, 5 ... | 2010 | 21142956 |
| yellow fever 17d-vectored vaccines expressing lassa virus gp1 and gp2 glycoproteins provide protection against fatal disease in guinea pigs. | yellow fever (yf) and lassa fever (lf) are two prevalent hemorrhagic fevers co-circulating in west africa and responsible for thousands of deaths annually. the yf vaccine 17d has been used as a vector for the lassa virus glycoprotein precursor (lasv-gpc) or their subunits, gp1 (attachment glycoprotein) and gp2 (fusion glycoprotein). cloning shorter inserts, lasv-gp1 and -gp2, between yf17d e and ns1 genes enhanced genetic stability of recombinant viruses, yf17d/lasv-gp1 and -gp2, in comparison w ... | 2010 | 21145373 |
| virology: one protein, many functions. | 2010 | 21150990 | |
| rapid detection of lassa virus by reverse transcription-loop-mediated isothermal amplification. | in this study, a simple one-step reverse transcription-loop-mediated isothermal amplification (rt-lamp) assay for rapid detection of lassa virus (lasv) was established. the two primer sets were designed to detect lasv circulating in sierra leone and northeastern nigeria. the rt-lamp assay using these primer sets was able to detect 100 copies of the in vitro transcribed artificial lasv rna within 25 min. the assay was also evaluated using intact viral rna extracted from cell culture-propagated vi ... | 2011 | 21175773 |
| decoding arenavirus pathogenesis: essential roles for alpha-dystroglycan-virus interactions and the immune response. | pathogenesis following a virus infection results from interactions between the virus and its host. the outcome is determined by tipping the balance between virulence of the virus or susceptibility/resistance of the host to favor one or the other. this review focuses on two important members of the old world arenavirus family: lassa fever virus (lfv), a robust human pathogen that causes a severe acute hemorrhagic disease; and lymphocytic choriomeningitis virus (lcmv), also a human pathogen but be ... | 2010 | 21185048 |
| current molecular epidemiology of lassa virus in nigeria. | recent lassa virus strains from nigeria were completely or partially sequenced. phylogenetic analysis revealed the predominance of lineage ii and iii strains, the existence of a previously undescribed (sub)lineage in nigeria, and the directional spread of virus in the southern part of the country. the bayesian analysis also provided estimates for divergence times within the lassa virus clade. | 2010 | 21191050 |
| 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 |
| 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 |
| lassa virus infection in nigeria: clinical perspective overview. | lassa fever is a severe, often fatal, hemorrhagic fever caused by lassa virus, an arenavirus that can be transmitted to humans from asymptomatically infected multimammate rats. the speculation is that lassa viral infection may affect between 2 to 3 million people each year in certain portions of the west african region, causing a mortality of about 10000 during the same period. lassa fever is one of the endemic zoonosis in nigeria with a high probability for nosocomial transmission due to severa ... | 2010 | 21287906 |
| 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 |
| 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 |
| 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 |
| medical microbiology | the hallmark of arenaviruses is their tendency to cause persistent silent infections in their natural hosts (rodents) and severe, often lethal, disseminated disease in humans. arenaviruses are pleomorphic enveloped particles that contain two rna segments of virus origin and ribosome-like components. suitable conditions for transmission of virus to humans occur in areas where humans come in contact with rodent urine that contains virus. persistent viremia and viruria in rodents result from a slow ... | 1996 | 21413313 |
| pathogenesis of lassa fever in cynomolgus macaques. | abstract: | 2011 | 21548931 |
| 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 |
| 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 |