Publications

effective vaccine for lassa fever.	lassa fever has been estimated to cause 5,000 deaths annually in west africa. recently, war in the zone where lassa fever is hyperendemic has severely impeded control and treatment. vaccination is the most viable control measure. there is no correlation between antibody levels and outcome in human patients, and inactivated vaccines produce high titers of antibodies to all viral proteins but do not prevent virus replication and death in nonhuman primates. accordingly, we vaccinated 44 macaques wi ...	2000	10888616
genetic diversity among lassa virus strains.	the arenavirus lassa virus causes lassa fever, a viral hemorrhagic fever that is endemic in the countries of nigeria, sierra leone, liberia, and guinea and perhaps elsewhere in west africa. to determine the degree of genetic diversity among lassa virus strains, partial nucleoprotein (np) gene sequences were obtained from 54 strains and analyzed. phylogenetic analyses showed that lassa viruses comprise four lineages, three of which are found in nigeria and the fourth in guinea, liberia, and sierr ...	2000	10888638
[conformational changes in lassa viral proteins when exposed to antibodies and complement].	addition of the complement to the antigen in lassa virus elisa stimulated the sensitivity and specificity of the assay. the effect depended on the mouse ig subclasses. elisa plate sensitization with igg2a and igg2b increased the sensitivity of elisa 8-16 times. protein footprinting data suggest that the complement c1q component stimulates antibody-induced conformation changes of the antigen.	2000	11200644
preliminary study on potential circulation of arenaviruses in the rodent population of nakhon pathom province, thailand and their medical importance in an evoluting environment.	preliminary serological investigations were prefered to detect evidence of arenavirus infection in rodents. the study examined virus antibody in 367 rodents trapped in 6 different geographical areas of nakhon pathom province, thailand from february-march, 1998. the overall seroprevalence among rodents was 13.3%, mostly in bandicota savilei (35.7%) and rattus norvegicus (31.5%). between ecology, behavior and sex of the rodents, seroprevalence was not significantly different (p>0.05), however the ...	2000	11023066
identification of a novel consensus sequence at the cleavage site of the lassa virus glycoprotein.	the lassa virus glycoprotein consists of an amino-terminal and a carboxy-terminal cleavage fragment designated gp-1 and gp-2, respectively, that are derived by proteolysis from the precursor gp-c. the membrane-anchored gp-2 obtained from purified virions of the josiah strain revealed the n-terminal tripeptide gtf(262) when analyzed by edman degradation. upstream of this site, gp-c contains the tetrapeptide sequence rrll(259), which is conserved in all lassa virus isolates published to date. syst ...	2000	11070044
[lassa fever].	a 22-year-old female german student was admitted with fever of unknown origin for 5 days to the hospital of her hometown immediately after returning from a 7-week journey under simple conditions through 4 west african countries. after exclusion of malaria and typhoid and nonrespondence to antibiosis, she was transferred on the 4th day to the department of tropical medicine in würzburg. after the clinical assumption of lassa fever, the virus was confirmed by pcr within 3 hours (bernhard nocht ins ...	2000	10935419
imported lassa fever in germany: molecular characterization of a new lassa virus strain.	we describe the isolation and characterization of a new lassa virus strain imported into germany by a traveler who had visited ghana, côte d'ivoire, and burkina faso. this strain, designated "av," originated from a region in west africa where lassa fever has not been reported. viral s rna isolated from the patient's serum was amplified and sequenced. a long-range reverse transcription polymerase chain reaction allowed amplification of the full-length (3.4 kb) s rna. the coding sequences of strai ...	2000	10998376
towards a human lassa fever vaccine.	arenaviruses, such as lassa fever, establish chronic infections in rodents, leading to incidental transmission to humans. lassa fever is a clinically severe disease, yet the absence of second attacks implies life-long immunity. the aim of this review is to consider whether such immunity could be provided by vaccines. the south american arenaviruses are controlled by neutralising antibody and a clinical trial of live, attenuated vaccine for argentinian haemorrhagic fever provided 84% protection. ...	2001	11590670
interaction of lyssaviruses with the low-affinity nerve-growth factor receptor p75ntr.	the low-affinity nerve-growth factor receptor p75ntr interacts in vitro with the rabies virus (rv) glycoprotein and serves as a receptor for rv. the lyssavirus genus comprises seven genotypes (gts) of rabies and rabies-related viruses. the ability of p75ntr to interact with the glycoprotein of representative lyssaviruses from each gt was investigated. this investigation was based on a specific binding assay between bsr cells infected with a lyssavirus and spodoptera frugiperda (sf21) cells expre ...	2001	11714960
antibodies to lassa virus z protein and nucleoprotein co-occur in human sera from lassa fever endemic regions.	it is not known whether the small 11-kda z protein of lassa virus is immunogenic during human lassa virus infection. to obtain evidence for the existence of an antibody response and to test the suitability of these antibodies for serosurveys, sera from lassa fever endemic regions (guinea and nigeria, n = 75) were tested for co-reactivity to z protein and nucleoprotein (np). sera from a non-endemic region (uganda, n = 50) served as a specificity control. z protein and np were expressed in escheri ...	2001	11599793
lassa fever in guinea: i. epidemiology of human disease and clinical observations.	the arenavirus lassa is found in west africa, where it sometimes causes a severe illness called lassa fever. lassa fever has been seldom investigated outside of a few hyperendemic regions, where the described epidemiology may differ from that in areas of low or moderate incidence of disease. through a prospective cohort study, we investigated the epidemiology and clinical presentation of lassa fever in guinea, where the disease has been infrequently recognized. a surveillance system was establis ...	2001	12653127
recent advances in vaccines against viral haemorrhagic fevers.	development of vaccines against viral haemorrhagic fevers is a public health priority. recent advances in our knowledge of pathogenesis and of the immune responses elicited by these viruses emphasize the crucial role of the immune system in the control of infection, but also its probable involvement in pathogenesis. several vaccine candidates against viral haemorrhagic fevers have been evaluated in animals during the past year. together, these data suggest that a vaccine approach against viral h ...	2001	11964870
lassa fever in guinea: ii. distribution and prevalence of lassa virus infection in small mammals.	rodents of the genus mastomys form the reservoir for lassa virus (lv), an arenavirus that causes a potentially severe hemorrhagic illness, lassa fever (lf). although mastomys rodents exist throughout sub-saharan africa, areas of human lf appear to be quite focal. the distribution of small mammals and lv-infected mastomys has been assessed in only a few countries. we conducted a survey of small mammals in selected regions of guinea to assess the degree to which lv poses a public health risk in th ...	2001	12653128
evidence of two lyssavirus phylogroups with distinct pathogenicity and immunogenicity.	the genetic diversity of representative members of the lyssavirus genus (rabies and rabies-related viruses) was evaluated using the gene encoding the transmembrane glycoprotein involved in the virus-host interaction, immunogenicity, and pathogenicity. phylogenetic analysis distinguished seven genotypes, which could be divided into two major phylogroups having the highest bootstrap values. phylogroup i comprises the worldwide genotype 1 (classic rabies virus), the european bat lyssavirus (ebl) ge ...	2001	11238853
the lassa virus glycoprotein precursor gp-c is proteolytically processed by subtilase ski-1/s1p.	the surface glycoprotein of the lassa virus, a member of the arenaviridae family, is synthesized as a 76-kda precursor (gp-c) that is posttranslationally cleaved into an n-terminal 44-kda subunit and a c-terminal membrane-anchored 36-kda subunit. cleavage occurs at the c-terminal end of the unusual recognition motif r-r-l-l. we show here that gp-c is cleaved in the endoplasmic reticulum by the cellular subtilase ski-1/s1p, an enzyme that has so far been observed to be involved in cholesterol met ...	2001	11606739
individual and bivalent vaccines based on alphavirus replicons protect guinea pigs against infection with lassa and ebola viruses.	lassa and ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. although lethal human disease outbreaks have been confined so far to sub-saharan africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into north america and europe. in the present study, we developed experimental individual vaccines for lassa virus and bivalent vaccines ...	2001	11689649
the model of response to viral haemorrhagic fevers of the national institute for infectious diseases "lazzaro spallanzani".	viral haemorrhagic fevers (vhf) are severe and life-threatening diseases caused by a range of viruses. however, only four agents of vhf are known to be readily capable of person-to-person spread: lassa virus, crimean/congo haemorrhagic fever virus, ebola and marburg viruses. diseases caused by these viruses are endemic only in few areas in the world, most notably africa and some rural parts of the middle east and eastern europe. nonetheless, the increasing volume of international travel presents ...	2001	11693443
mucosal immunization with salmonella typhimurium expressing lassa virus nucleocapsid protein cross-protects mice from lethal challenge with lymphocytic choriomeningitis virus.	lassa fever virus (las) is transmitted to man by rodent carriers and is fatal in a third of untreated cases. our goal is to provide immune protection from lassa fever by mucosal vaccination.	2001	11437313
lassa fever encephalopathy: lassa virus in cerebrospinal fluid but not in serum.	the pathogenesis of neurologic complications of lassa fever is poorly understood. a nigerian patient had fever, disorientation, seizures, and blood-brain barrier dysfunction, and lassa virus was found in cerebrospinal fluid (csf) but not in serum. the concentration of lassa virus rna in csf corresponded to 1 x 10(3) pfu/ml, as determined by a quantitative real-time polymerase chain reaction assay. to characterize the lassa virus in csf, the 3.5-kb s rna was sequenced. in the s rna coding sequenc ...	2001	11443561
self-assembly properties of a model ring domain.	ring domains act in a variety of essential cellular processes but have no general function ascribed to them. here, we observe that purified arenaviral protein z, constituted almost entirely by its ring domain, self-assembles in vitro into spherical structures that resemble functional bodies formed by z in infected cells. by using a variety of biophysical methods we provide a thermodynamic and kinetic framework for the ring-dependent self-assembly of z. assembly appears coupled to substantial con ...	2002	11792829
monitoring of clinical and laboratory data in two cases of imported lassa fever.	during 2000, four cases of fatal lassa fever were imported from africa to europe. in two patients, consecutive serum samples were available for monitoring of virus load and cytokine levels in addition to standard laboratory data. both patients had non-specific early clinical symptoms including high fever. patient 1 developed multi-organ failure and died of hemorrhagic shock on day 15 of illness, while patient 2 died of respiratory failure due to aspiration without hemorrhage on day 16. ribavirin ...	2002	11825774
rapid detection and quantification of rna of ebola and marburg viruses, lassa virus, crimean-congo hemorrhagic fever virus, rift valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription-pcr.	viral hemorrhagic fevers (vhfs) are acute infections with high case fatality rates. important vhf agents are ebola and marburg viruses (mbgv/ebov), lassa virus (lasv), crimean-congo hemorrhagic fever virus (cchfv), rift valley fever virus (rvfv), dengue virus (denv), and yellow fever virus (yfv). vhfs are clinically difficult to diagnose and to distinguish; a rapid and reliable laboratory diagnosis is required in suspected cases. we have established six one-step, real-time reverse transcription- ...	2002	12089242
new world arenavirus clade c, but not clade a and b viruses, utilizes alpha-dystroglycan as its major receptor.	alpha-dystroglycan (alpha-dg) has been identified as a major receptor for lymphocytic choriomeningitis virus (lcmv) and lassa virus, two old world arenaviruses. the situation with new world arenaviruses is less clear: previous studies demonstrated that oliveros virus also exhibited high-affinity binding to alpha-dg but that guanarito virus did not. to extend these initial studies, several additional old and new world arenaviruses were screened for entry into mouse embryonic stem cells possessing ...	2002	11967329
lassa fever.		2002	11987809
[a man with fatal lassa fever following a stay in sierra leone].	a 48-year-old-man returned to the netherlands from sierra leone and was admitted with nausea, crampy abdominal pain, myalgia, arthralgia, headache and watery diarrhoea. this was the first case of lassa fever diagnosed in the netherlands since 1980. despite treatment with ribavirin, the patient died on the 16th day of illness. prompt diagnosis of lassa fever is critical for the timely administration of ribavirin which improves diagnosis considerably, and for the timely implementation of isolation ...	2002	12467165
a rapid fluorometric assay for the proteolytic activity of ski-1/s1p based on the surface glycoprotein of the hemorrhagic fever lassa virus.	the subtilase subtilisin kexin isozyme-1 (ski-1)/site 1 protease (s1p), has been implicated in the processing of lassa virus glycoprotein c (gp-c) precursor into gp1 and gp2 that are responsible for viral fusion with the host cell membrane. here, we studied in vitro the kinetics of this cleavage by hski-1 using an intramolecularly quenched fluorogenic (iqf) peptide, q-gpc(251-263) [abz-(251)asp-ile-tyr-ile-ser-arg-arg-leu-leu/gly-thr-phe-thr(263)-3-nitrotyr-ala-conh(2)], containing the identifie ...	2002	11943176
[immunogenic and protective characteristics of recombinant lassa virus np protein].	recombinant fragment of lassa virus (strain josiah) nucleocapsid protein (corresponding to amino acid residues 141 + 569) constructed by dr. jan ter meulen (tropenmedizine, hamburg) was used for immunizing cba/calac mice. the preparation was injected intraperitoneally twice with 2-week interval in a dose of 10 micrograms. the parameters of the resultant specific humoral and cell-mediated immunity were comparable to those in reference animals immunized with inactivated lassa virus. challenge with ...	2002	12046464
rabies, lassaviruses and bats.		2003	14702840
[use of guinea pigs for assessing the efficacy of vaccines against lassa fever].	the use of guinea pigs as a laboratory model was proven to be appropriate in investigating the vaccines developed against lassa fever at the preclinical study stage. an adapted variant of lassa virus was cultivated, which caused death of guinea pigs with respect for an agent's dose. finally, it was shown to be possible to investigate the immunogenic and protective properties of the inactivated antigen of lassa virus in experiments with guinea pigs.	2003	14708232
a system of protein target sequences for anti-rna-viral chemotherapy by a vitamin b6-derived zinc-chelating trioxa-adamantane-triol.	the synthesis of the structurally unusual heterotricyclic compound 1-[3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinyl]-2,8,9-trioxaadamantane-3,5,7-triol (trivially named bananin, bn) from pyridoxylidenephloroglucinol and a theoretical prospect on possible biological activities of bn are presented in this report. pyridoxylidenephloroglucinol is synthesized by knoevenagel condensation of the vitamin b6 aldehyde pyridoxal with phloroglucinol. pyridoxylidenephloroglucinol rearranges to light-yello ...	2003	14527557
lassa virus z protein is a matrix protein and sufficient for the release of virus-like particles [corrected].	lassa virus is an enveloped virus with glycoprotein spikes on its surface. it contains an rna ambisense genome that encodes the glycoprotein precursor gp-c, the nucleoprotein np, the polymerase l, and the z protein. here we demonstrate that the lassa virus z protein (i). is abundant in viral particles, (ii). is strongly membrane associated, (iii). is sufficient in the absence of all other viral proteins to release enveloped particles, and (iv). contains two late domains, ptap and ppxy, necessary ...	2003	12970458
arenaviruses other than lassa virus.	the family arenaviridae includes 23 viral species, of which 5 can cause viral hemorrhagic fevers with a case fatality rate of about 20%. these five viruses are junin, machupo, guanarito, sabia and lassa virus, the manipulation of which requires biosafety level 4 facilities. they are included in the category a pathogen list established by the center for disease control and prevention that groups agents with the greatest potential for adverse public health impact and mass casualties whether a situ ...	2003	12615305
imported lassa fever in germany: surveillance and management of contact persons.	this study sought to assess the risk of secondary transmission after import of lassa fever into europe. a total of 232 persons exposed to a case of lassa fever imported into germany were identified. the level of exposure was determined for 157 persons (68%), and 149 (64%) were tested serologically. high-risk or close contact was reported by 30 (19%) of 157 persons. no symptomatic secondary infections were observed. however, lassa virus-specific immunoglobulin g antibodies were detected in a seru ...	2003	12746770
crimean-congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase ski-1.	crimean-congo hemorrhagic fever (cchf) virus is a tick-borne member of the genus nairovirus, family bunyaviridae. the mature virus glycoproteins, gn and gc (previously referred to as g2 and g1), are generated by proteolytic cleavage from precursor proteins. the amino termini of gn and gc are immediately preceded by tetrapeptides rrll and rkpl, respectively, leading to the hypothesis that ski-1 or related proteases may be involved (a. j. sanchez, m. j. vincent, and s. t. nichol, j. virol. 76:7263 ...	2003	12885882
phylogenetic analysis reveals a low rate of homologous recombination in negative-sense rna viruses.	recombination is increasingly seen as an important means of shaping genetic diversity in rna viruses. however, observed recombination frequencies vary widely among those viruses studied to date, with only sporadic occurrences reported in rna viruses with negative-sense genomes. to determine the extent of homologous recombination in negative-sense rna viruses, phylogenetic analyses of 79 gene sequence alignments from 35 negative-sense rna viruses (a total of 2154 sequences) were carried out. powe ...	2003	13679603
identification of lassa virus glycoprotein signal peptide as a trans-acting maturation factor.	lassa virus glycoprotein is translated as a precursor (pre-gp-c) into the lumen of the endoplasmic reticulum and is cotranslationally cleaved into the signal peptide and gp-c, before gp-c is proteolytically processed into its subunits gp1 and gp2. the signal peptide of pre-gp-c comprises 58 amino acids. the substitution of lassa virus pre-gp-c signal peptide with another signal peptide still mediates translocation and the release of signal peptide but abolishes the proteolytic cleavage of gp-c i ...	2003	14555961
signal peptide of lassa virus glycoprotein gp-c exhibits an unusual length.	lassa virus glycoprotein is synthesized as precursor gp-c into the lumen of the endoplasmic reticulum and cleaved posttranslationally into the n-terminal subunit gp-1 and the c-terminal subunit gp-2 by subtilase ski-1/s1p. the n-terminal portion of the primary translation product pregp-c contains a signal peptide of unknown length. in order to demonstrate the signal peptide cleavage site, purified viral gp-1 isolated from lassa virus particles was n-terminally sequenced as tslykgv, identical to ...	2003	12633879
cutting edge: impairment of dendritic cells and adaptive immunity by ebola and lassa viruses.	acute infection of humans with ebola and lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as tnf-alpha, il-1 beta, and il-6, vs late stage infections, which are associated with poor immune responses. the mechanisms underlying these diverse outcomes are poorly understood. in particular, the role played by cells of the innate immune system, ...	2003	12626527
arenavirus-mediated liver pathology: acute lymphocytic choriomeningitis virus infection of rhesus macaques is characterized by high-level interleukin-6 expression and hepatocyte proliferation.	lymphocytic choriomeningitis virus (lcmv) and lassa virus can cause hemorrhagic fever and liver disease in primates. the we strain of lcmv (lcmv-we) causes a fatal lassa fever-like disease in rhesus macaques and provides a model for arenavirus pathogenesis in humans. lcmv-we delivered intravenously or intragastrically to rhesus macaques targets hepatocytes and induces high levels of liver enzymes, interleukin-6 (il-6), soluble il-6 receptor (sil-6r), and soluble tumor necrosis factor receptors ( ...	2003	12525606
molecular diagnostics of viral hemorrhagic fevers.	this review addresses the diagnostics of viral hemorrhagic fevers (vhfs). in the first part, an overview is given on classical methods of vhf diagnostics as well as novel molecular diagnostic tools. currently available polymerase chain reaction (pcr) assays for diagnosis of vhf are summarized and discussed. in the second part, vhf diagnostics are described in particular for lassa fever, yellow fever, and crimean-congo hemorrhagic fever, based on cases that were imported into or occurred within e ...	2003	12615304
[lassa virus].		2003	12718025
first international quality assurance study on the rapid detection of viral agents of bioterrorism.	we have conducted an international quality assurance study of filovirus, lassa virus, and orthopox virus pcr with 24 participants. of the participating laboratories, 45.8 and 66.7% detected virus in all plasma samples, which contained > or = 5,000 and > or = 100,000 copies per ml, respectively. sensitivity levels were not significantly different between viruses. false-negative results were attributable to a lack of sensitivity.	2004	15071040
correction: stampidine prevents mortality in an experimental mouse model of viral hemorrhagic fever caused by lassa virus.		2004	15171793
human macrophages, but not dendritic cells, are activated and produce alpha/beta interferons in response to mopeia virus infection.	lassa virus (lv) and mopeia virus (mv) are closely related members of the arenavirus genus, sharing 75% amino acid sequence identity. however, lv causes hemorrhagic fever in humans and nonhuman primates, whereas mv cannot induce disease. we have previously shown that antigen-presenting cells (apc)-macrophages (mp) and dendritic cells (dc)-sustain high replication rates of lv but are not activated, suggesting that they play a role in the immunosuppression observed in severe cases of lassa fever. ...	2004	15367618
imported lassa fever--new jersey, 2004.	lassa fever is an acute viral illness caused by lassa virus, which is hosted by rodents in the mastomys natalensis species complex and rarely imported to countries outside of those areas in africa where the disease is endemic. lassa fever is characterized by fever, muscle aches, sore throat, nausea, vomiting, and chest and abdominal pain. approximately 15%-20% of patients hospitalized for lassa fever die from the illness; however, approximately 80% of human infections with lassa virus are mild o ...	2004	15457145
lassa virus.	lassa virus is a rna virus belonging to the family of arenaviridae. it was discovered as the causative agent of a hemorrhagic fever--lassa fever--about 30 years ago. lassa fever is endemic in west africa and is estimated to affect some 100,000 people annually. great progress in the understanding of the life cycle of arenaviruses, including lassa virus, has been made in recent years. new insights have been gained in the pathogenesis and molecular epidemiology of lassa fever, and state-of the-art ...	2004	15487592
replicon system for lassa virus.	lassa virus is endemic to west africa and causes hemorrhagic fever in humans. to facilitate the functional analysis of this virus, a replicon system was developed based on lassa virus strain av. genomic and antigenomic minigenomes (mg) were constructed consisting of the intergenic region of s rna and a reporter gene (renilla luciferase) in antisense orientation, flanked by the 5' and 3' untranslated regions of s rna. mgs were expressed under the control of the t7 promoter. nucleoprotein (np), l ...	2004	15564487
lassa fever vaccine.	lassa fever remains a serious challenge to public health in west africa threatening both local residents in rural areas and those who serve them, particularly medical care providers. given the ecology of the rodent host and conditions in the endemic area, a vaccine is mandatory for control. the challenge is to overcome the scientific, political and economic obstacles to producing a human use vaccine candidate. there are some scientific issues to resolve. it is known that the g-protein confers pr ...	2004	15056044
lassa virus glycoprotein signal peptide displays a novel topology with an extended endoplasmic reticulum luminal region.	lassa virus glycoprotein c (gp-c) is translated as a precursor (pregp-c) into the lumen of the endoplasmic reticulum (er) and cotranslationally cleaved into the signal peptide and immature gp-c before gp-c is proteolytically processed into its subunits, gp-1 and gp-2, which form the mature virion spikes. the signal peptide of pregp-c comprises 58 amino acids and contains two distinct hydrophobic domains. here, we show that each hydrophobic domain alone can insert pregp-c into the er membrane. fu ...	2004	14709548
characterization of the lassa virus matrix protein z: electron microscopic study of virus-like particles and interaction with the nucleoprotein (np).	lassa virus is the causative agent of a hemorrhagic fever endemic in west africa. the rna genome of lassa virus encodes the glycoprotein precursor gp-c, a nucleoprotein (np), the viral polymerase l and a small protein z (11 kda). here, we analyze the role of z protein for virus maturation. we have recently shown that expression of z protein in the absence of other viral proteins is sufficient for the release of enveloped z-containing particles. in this study, we examined particles secreted into ...	2004	15019244
properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses.	replication-competent recombinant vesicular stomatitis viruses (rvsvs) expressing the type i transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (marburg virus, ebola virus, and lassa virus) were generated and characterized. all recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. unlike the rvsvs with an additional transcription unit expressing the soluble glycoproteins, the viruses carrying the ...	2004	15113924
stampidine prevents mortality in an experimental mouse model of viral hemorrhagic fever caused by lassa virus.	the potential use of microorganisms as agents of biological warfare (bw) is a growing concern. lassa virus, a member of the arenavirus class of hemorrhagic fever (hf) viruses has emerged as a worldwide concern among public health officials. the purpose of the present study was to further elucidate the antiviral activity spectrum of stampidine, a novel nucleoside analog with potent anti-viral activity against the immunodeficiency viruses hiv-1, hiv-2, and fiv, by examining its effects on survival ...	2004	14720304
lcmv-mediated hepatitis in rhesus macaques: we but not arm strain activates hepatocytes and induces liver regeneration.	lymphocytic chorimeningitis virus (lcmv), the prototype arenavirus, and lassa virus (lasv), causative agent of lassa hemorrhagic fever (lhf), belong to the old world group of the family arenaviridae. both viruses have extensive strain diversity and significant variations in lethality and pathogenicity for man and experimental animals. we have shown that the lhf-like infection of rhesus macaques with the we strain of lcmv affects liver functions, induces hepatocyte proliferation, and causes a ris ...	2004	15338320
cells expressing the ring finger z protein are resistant to arenavirus infection.	arenaviruses include lassa fever virus (lfv) and the south american hemorrhagic fever viruses. these viruses cause severe human disease, and they pose a threat as agents of bioterrorism. arenaviruses are enveloped viruses with a bisegmented negative-strand rna genome whose proteomic capability is limited to four polypeptides: nucleoprotein (np); surface glycoprotein (gp), which is proteolytically processed into gp1 and gp2; polymerase (l); and a small (11-kda) ring finger protein (z). our invest ...	2004	14990716
inhibition of different lassa virus strains by alpha and gamma interferons and comparison with a less pathogenic arenavirus.	the high pathogenicity of lassa virus is assumed to involve resistance to the effects of interferon (ifn). we have analyzed the effects of alpha ifn (ifn-alpha), ifn-gamma, and tumor necrosis factor alpha (tnf-alpha) on replication of lassa virus compared to the related, but less pathogenic, lymphocytic choriomeningitis virus (lcmv). three low-passage lassa virus strains (av, nl, and csf), isolated from humans with mild to fulminant lassa fever, were tested. lassa virus replication was inhibited ...	2004	14990737
lassa virus infection of human dendritic cells and macrophages is productive but fails to activate cells.	lassa fever is a hemorrhagic fever caused by lassa virus (lv), an old-world arenavirus. little is known about the immune responses that occur during the disease, but protection seems to be linked to the induction of cellular responses specific for viral glycoproteins. conversely, severe lassa fever may be associated with immunosuppression. we studied the infection of human dendritic cells (dc) and macrophages (mp) by lv. both these cell types are susceptible to lv infection. viral nucleoprotein ...	2004	14978087
old and new world arenaviruses share a highly conserved epitope in the fusion domain of the glycoprotein 2, which is recognized by lassa virus-specific human cd4+ t-cell clones.	data from human studies and animal experiments indicate a dominant role of t-cells over antibodies in controlling acute lassa virus infection and providing immunity to reinfection. knowledge of the epitopes recognized by t-cells may therefore be crucial to the development of a recombinant lassa virus vaccine. in order to study human t-cell reactivity to the most conserved structural protein of lassa virus, the glycoprotein 2 (gp2), seven gp2-specific cd4+ t-cell clones (tccs) were generated from ...	2004	15033572
application of real-time pcr for testing antiviral compounds against lassa virus, sars coronavirus and ebola virus in vitro.	this report describes the application of real-time pcr for testing antivirals against highly pathogenic viruses such as lassa virus, sars coronavirus and ebola virus. the test combines classical cell culture with a quantitative real-time pcr read-out. the assay for lassa virus was validated with ribavirin, which showed an ic(50) of 9 micrograms/ml. small-scale screening identified a class of imidazole nucleoside/nucleotide analogues with antiviral activity against lassa virus. the analogues cont ...	2004	15451189
myristoylation of the ring finger z protein is essential for arenavirus budding.	the arenavirus small ring finger z protein is the main driving force of arenavirus budding. the primary structure of z is devoid of hydrophobic transmembrane domains, but both lymphocytic choriomeningitis virus (lcmv) and lassa fever virus z proteins accumulate near the inner surface of the plasma membrane and are strongly membrane associated. all known arenavirus z proteins contain a glycine (g) at position 2, which is a potential acceptor site for a myristoyl moiety. metabolic labeling showed ...	2004	15452271
[viral hemorrhagic fevers--ebola hemorrhagic fever, marburg virus disease, and lassa fever].		2004	15624463
sequence analysis of l rna of lassa virus.	the l rna of three lassa virus strains originating from nigeria, ghana/ivory coast, and sierra leone was sequenced and the data subjected to structure predictions and phylogenetic analyses. the l gene products had 2218-2221 residues, diverged by 18% at the amino acid level, and contained several conserved regions. only one region of 504 residues (positions 1043-1546) could be assigned a function, namely that of an rna polymerase. secondary structure predictions suggest that this domain is very s ...	2004	14972544
lassa virus: seroepidemiological survey of rodents caught in ekpoma and environs.	of the 876 rodents caught in different parts of ekpoma, nigeria, and environs, 218 were mastomys natalensis, while 658 were other rodents. of the 218 m. natalensis caught, 102 (46.79%) were positive for complement fixing antibody to lassa virus.	2005	15712534
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
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
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
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
taking down goliaths: new vaccines may spell the end for ebola, marburg and lassa virus infections.		2005	16323509
[lissavirus in bats residing in the south of west siberia].	we caught, 2002-2003 in caves of novosibirsk region and altai territory, 52 bats (myotis daubentoni, myotis brandtii, murina leucogaster, plecotus auritus). examinations of the animals' brain samples by fluorescence antibody microscopy and rt-pcr revealed lyssaviruses, genotype 1, which were close to strains provoking rabies in the local animals. according to the results, bats can be involved in keeping alive the rabies foci in western siberia, which must be taken into account in antiepizootic m ...	2005	15747869
sonja buckley.		2005	15786567
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
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
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
lassa fever, nigeria, 2003 and 2004.		2005	16355508
some tolerance for fur--animal studies in plos medicine.		2005	15971961
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
[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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
viral haemorrhagic fevers caused by lassa, ebola and marburg viruses.		2006	16802617
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
[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 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
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
[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
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
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
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
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