Publications

lassa fever - full recovery without ribavarin treatment: a case report.	lassa fever is a rodent-borne zoonosis that clinically manifests as an acute hemorrhagic fever. it is treated using ribavarin. surviving lassa fever without receiving the antiviral drug ribavarin is rare. only few cases have been documented to date.	2014	25834520
lassa fever in post-conflict sierra leone.	lassa fever (lf), an often-fatal hemorrhagic disease caused by lassa virus (lasv), is a major public health threat in west africa. when the violent civil conflict in sierra leone (1991 to 2002) ended, an international consortium assisted in restoration of the lf program at kenema government hospital (kgh) in an area with the world's highest incidence of the disease.	2014	24651047
production of cxc and cc chemokines by human antigen-presenting cells in response to lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with lassa fever.	the pathogenesis of lassa fever (lf), a hemorrhagic fever endemic to west africa, remains unclear. we previously compared lassa virus (lasv) with its genetically close, but nonpathogenic homolog mopeia virus (mopv) and demonstrated that the strong activation of antigen-presenting cells (apc), including type i ifn production, observed in response to mopv probably plays a crucial role in controlling infection. we show here that human macrophages (mp) produce large amounts of cc and cxc chemokines ...	2014	24421914
genetic variation in vitro and in vivo of an attenuated lassa vaccine candidate.	the attenuated lassa vaccine candidate ml29 is a laboratory-produced reassortant between lassa and mopeia viruses, two old world arenaviruses that differ by 40% in nucleic acid sequence. in our previous studies, ml29 elicited sterilizing immunity against lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (siv)-infected and uninfected rhesus macaques. here, we show that ml29 is stable after 12 passages in vitro withou ...	2014	24335292
simian hemorrhagic fever virus cell entry is dependent on cd163 and uses a clathrin-mediated endocytosis-like pathway.	simian hemorrhagic fever virus (shfv) causes a severe and almost uniformly fatal viral hemorrhagic fever in asian macaques but is thought to be nonpathogenic for humans. to date, the shfv life cycle is almost completely uncharacterized on the molecular level. here, we describe the first steps of the shfv life cycle. our experiments indicate that shfv enters target cells by low-ph-dependent endocytosis. dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin a dra ...	2015	25355889
international external quality assessment study for molecular detection of lassa virus.	lassa virus (lasv) is a causative agent of hemorrhagic fever in west africa. in recent years, it has been imported several times to europe and north america. the method of choice for early detection of lasv in blood is rt-pcr. therefore, the european network for diagnostics of 'imported' viral diseases (enivd) performed an external quality assessment (eqa) study for molecular detection of lasv. a proficiency panel of 13 samples containing various concentrations of inactivated lasv strains josiah ...	2015	25996783
molecular mechanism for lamp1 recognition by lassa virus.	lassa virus is a notorious human pathogen that infects many thousands of people each year in west africa, causing severe viral hemorrhagic fevers and significant mortality. the surface glycoprotein of lassa virus mediates receptor recognition through its gp1 subunit. here we report the crystal structure of gp1 from lassa virus, which is the first representative gp1 structure for old world arenaviruses. we identify a unique triad of histidines that forms a binding site for lamp1, a known lysosoma ...	2015	25972533
a recombinant vesicular stomatitis virus-based lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct lassa viruses.	lassa virus (lasv) is endemic in several west african countries and is the etiological agent of lassa fever. despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. genetically, lasv demonstrates a high degree of diversity that correlates with geographic distribution. the genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of ...	2015	25884628
insight into the binding modes of lassa nucleoprotein complexed with ssrna by molecular dynamic simulations and free energy calculations.	lassa virus (lasv), an arenavirus known to be responsible for a severe hemorrhagic fever, causes thousands of deaths annually and there is no effective vaccine for it so far. the nucleoprotein (np) of lasv plays an essential role in the replication and transcription of the viral genome. recent research shows that viral rna binds in a deep crevice located within the n-terminal domain of np and suggests a gating mechanism in which np transforms from a "closed" position to an "open" position to bin ...	2015	24824824
sequence variability and geographic distribution of lassa virus, sierra leone.	lassa virus (lasv) is endemic to parts of west africa and causes highly fatal hemorrhagic fever. the multimammate rat (mastomys natalensis) is the only known reservoir of lasv. most human infections result from zoonotic transmission. the very diverse lasv genome has 4 major lineages associated with different geographic locations. we used reverse transcription pcr and resequencing microarrays to detect lasv in 41 of 214 samples from rodents captured at 8 locations in sierra leone. phylogenetic an ...	2015	25811712
cis- and cell-type-dependent trans-requirements for lassa virus-like particle production.	lassa virus (lasv) small zinc-finger protein (z), which contains two l-domain motifs, plays a central role in virus budding. here, we report that co-expression of glycoprotein (gpc) altered the requirements for cholesterol but not the l-domains and host factor, tsg101, for z-induced virus-like particle (vlp) production. in particular, the cholesterol requirement for vlp production was cell-type-dependent. in addition, gpc was found to be important for co-localization of z with cd63, a late endos ...	2015	25722347
vesicular stomatitis virus-based vaccines against lassa and ebola viruses.	we demonstrated that previous vaccination with a vesicular stomatitis virus (vsv)-based lassa virus vaccine does not alter protective efficacy of subsequent vaccination with a vsv-based ebola virus vaccine. these findings demonstrate the utility of vsv-based vaccines against divergent viral pathogens, even when preexisting immunity to the vaccine vector is present.	2015	25625358
gairo virus, a novel arenavirus of the widespread mastomys natalensis: genetically divergent, but ecologically similar to lassa and morogoro viruses.	despite its near pan-african range, the natal multimammate mouse, mastomys natalensis, carries the human pathogen lassa virus only in west africa, while the seemingly non-pathogenic arenaviruses mopeia, morogoro, and luna have been detected in this semi-commensal rodent in mozambique/zimbabwe, tanzania and zambia, respectively. here, we describe a novel arenavirus in m. natalensis from gairo district of central tanzania, for which we propose the name "gairo virus". surprisingly, the virus is not ...	2015	25559385
delayed inflammatory and cell death responses are associated with reduced pathogenicity in lujo virus-infected cynomolgus macaques.	to identify host factors associated with arenavirus virulence, we used a cynomolgus macaque model to evaluate the pathogenesis of lujo virus (lujv), a recently emerged arenavirus that caused an outbreak of severe viral hemorrhagic fever in southern africa. in contrast to human cases, lujv caused mild, nonlethal illness in macaques. we then compared this to contrasting clinical outcomes during arenavirus infection, specifically to samples obtained from macaques infected with three highly pathogen ...	2015	25520505
mapping the zoonotic niche of lassa fever in africa.	lassa fever is a viral haemorrhagic illness responsible for disease outbreaks across west africa. it is a zoonosis, with the primary reservoir species identified as the natal multimammate mouse, mastomys natalensis. the host is distributed across sub-saharan africa while the virus' range appears to be restricted to west africa. the majority of infections result from interactions between the animal reservoir and human populations, although secondary transmission between humans can occur, particul ...	2015	26085474
shedding dynamics of morogoro virus, an african arenavirus closely related to lassa virus, in its natural reservoir host mastomys natalensis.	arenaviruses can cause mild to severe hemorrhagic fevers. humans mainly get infected through contact with infected rodents or their excretions, yet little is known about transmission dynamics within rodent populations. morogoro virus (morv) is an old world arenavirus closely related to lassa virus with which it shares the same host species mastomys natalensis. we injected morv in its host, and sampled blood and excretions at frequent intervals. infection in adults was acute; viral rna disappeare ...	2015	26022445
lassa fever or lassa hemorrhagic fever risk to humans from rodent-borne zoonoses.	viral hemorrhagic fevers (vhfs) typically manifest as rapidly progressing acute febrile syndromes with profound hemorrhagic manifestations and very high fatality rates. lassa fever, an acute hemorrhagic fever characterized by fever, muscle aches, sore throat, nausea, vomiting, diarrhea and chest and abdominal pain. rodents are important reservoirs of rodent-borne zoonosis worldwide. transmission rodents to humans occur by aerosol spread, either from the genus mastomys rodents' excreta (multimamm ...	2015	26012219
immune evasion mechanisms of arenaviruses.		2015	26595677
lassa virus isolates from mali and the ivory coast represent an emerging fifth lineage.	previous imported cases of lassa fever (lf) into the united kingdom from the ivory coast and mali, as well as the detection of lassa virus (lasv) among the mastomys natalensis population within mali has led to the suggestion that the endemic area for lf is expanding. initial phylogenetic analyses arrange isolates from mali and the ivory coast separately from the classical lineage iv isolates taken from sierra leone, guinea, and liberia. the availability of full genome sequences continues to incr ...	2015	26483768
immunosuppressive arenaviral exoribonuclease.		2015	26468986
arenavirus glycan shield promotes neutralizing antibody evasion and protracted infection.	arenaviruses such as lassa virus (lasv) can cause severe hemorrhagic fever in humans. as a major impediment to vaccine development, delayed and weak neutralizing antibody (nab) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. to investigate the mechanisms underlying arenavirus nab evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. we performed neutralization tests with sera fr ...	2015	26587982
animal model of sensorineural hearing loss associated with lassa virus infection.	approximately one-third of lassa virus (lasv)-infected patients develop sensorineural hearing loss (snhl) in the late stages of acute disease or in early convalescence. with 500,000 annual cases of lassa fever (lf), lasv is a major cause of hearing loss in regions of west africa where lf is endemic. to date, no animal models exist that depict the human pathology of lf with associated hearing loss. here, we aimed to develop an animal model to study lasv-induced hearing loss using human isolates f ...	2015	26719273
in silico prediction of b- and t- cell epitope on lassa virus proteins for peptide based subunit vaccine design.	lassa fever is a severe, often-fatal and one of the most virulent disease in primates. however, the mechanism of escape of virus from the t-cell mediated immune response of the host cell is not explained in any studies yet. in our studies we had aimed to predict b- and t- cell epitope of lassa virus protein, for impaling the futuristic approach of developing preventive measures against this disease, further we can also study its presumed viral- host mechanism.	2015	26601089
lassa virus in multimammate rats, côte d'ivoire, 2013.		2015	26196447
the broad-spectrum antiviral favipiravir protects guinea pigs from lethal lassa virus infection post-disease onset.	with up to 500,000 infections annually, lassa virus (lasv), the cause of lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (vhf) in humans. lasv is endemic in several west african countries with sporadic cases and prolonged outbreaks observed most commonly in sierra leone, liberia, guinea and nigeria. additionally several cases of lassa fever have been imported into north america, europe and asia making lasv a global threat to public health. despite this, cu ...	2015	26456301
general molecular strategy for development of arenavirus live-attenuated vaccines.	hemorrhagic fever arenaviruses (hfa) pose important public health problems in regions where they are endemic. thus, lassa virus (lasv) infects several hundred thousand individuals yearly in west africa, causing a large number of lassa fever cases associated with high morbidity and mortality. concerns about human-pathogenic arenaviruses are exacerbated because of the lack of fda-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin tha ...	2015	26401045
viral evolution: the history of lassa virus.		2015	26299786
[epidemiology of ebola virus disease and of other highly contagious, life-threatening diseases with low incidence in germany].	apart from sporadic exported cases, the occurrence of ebola, marburg and lassa virus diseases is limited to the african continent. crimean-congo hemorrhagic fever occurs in southeastern europe but, so far, not in germany. other hemorrhagic fever disease-viruses occur in distinct regions in south america. pulmonary plague is the bacterial infectious disease with the most contagious and lethal course and it is endemic to madagascar and east africa, but also occurs in other countries (e.g. india, u ...	2015	25997608
research efforts to control highly pathogenic arenaviruses: a summary of the progress and gaps.	significant progress has been made in the past 10 years in unraveling the molecular biology of highly pathogenic arenaviruses that are endemic in several west african countries (lassa fever virus) and in some regions of south america (argentine and bolivian hemorrhagic fever viruses). while this has resulted in proof-of-concept studies of novel vaccine candidates in non-human primates and in the discovery of several novel antiviral small molecule drug candidates, none of them has been tested in ...	2015	25549822
lassa-vesicular stomatitis chimeric virus safely destroys brain tumors.	high-grade tumors in the brain are among the deadliest of cancers. here, we took a promising oncolytic virus, vesicular stomatitis virus (vsv), and tested the hypothesis that the neurotoxicity associated with the virus could be eliminated without blocking its oncolytic potential in the brain by replacing the neurotropic vsv glycoprotein with the glycoprotein from one of five different viruses, including ebola virus, marburg virus, lymphocytic choriomeningitis virus (lcmv), rabies virus, and lass ...	2015	25878115
human hemorrhagic fever causing arenaviruses: molecular mechanisms contributing to virus virulence and disease pathogenesis.	arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (lcmv) to highly virulent hemorrhagic fever (hf) causing viruses such as lassa (lasv), junin (junv), machupo (macv), lujo (lujv), sabia (sabv), guanarito (gtov), and chapare (chpv), for which there are limited preventative and therapeutic measures. why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an e ...	2015	26011826
clinical sequencing uncovers origins and evolution of lassa virus.	the 2013-2015 west african epidemic of ebola virus disease (evd) reminds us of how little is known about biosafety level 4 viruses. like ebola virus, lassa virus (lasv) can cause hemorrhagic fever with high case fatality rates. we generated a genomic catalog of almost 200 lasv sequences from clinical and rodent reservoir samples. we show that whereas the 2013-2015 evd epidemic is fueled by human-to-human transmissions, lasv infections mainly result from reservoir-to-human infections. we elucidat ...	2015	26276630
emerging intracellular receptors for hemorrhagic fever viruses.	ebola virus and lassa virus belong to different virus families that can cause viral hemorrhagic fever, a life-threatening disease in humans with limited treatment options. to infect a target cell, ebola and lassa viruses engage receptors at the cell surface and are subsequently shuttled into the endosomal compartment. upon arrival in late endosomes/lysosomes, the viruses trigger membrane fusion to release their genome into the cytoplasm. although contact sites at the cell surface were recognized ...	2015	26004032
hunting viral receptors using haploid cells.	viruses have evolved intricate mechanisms to gain entry into the host cell. identification of host proteins that serve as viral receptors has enabled insights into virus particle internalization, host and tissue tropism, and viral pathogenesis. in this review we discuss the most commonly employed methods for virus receptor discovery, specifically highlighting the use of forward genetic screens in human haploid cells. the ability to generate true knockout alleles at high saturation provides a sen ...	2015	26958914
discovery of novel rhabdoviruses in the blood of healthy individuals from west africa.	next-generation sequencing (ngs) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (uafi) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen's nucleic acid sequence. more generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. we have used ngs to identify rna viruse ...	2015	25781465
lessons learnt from the management of a case of lassa fever and follow-up of nosocomial primary contacts in nigeria during ebola virus disease outbreak in west africa.	to describe our experiences in the management of a case of lassa fever (lf) and follow-up of nosocomial primary contacts during the 2014 ebola outbreak in west africa.	2015	26171669
imported lassa fever: a report of 2 cases in ghana.	lassa fever is a potentially fatal acute viral illness caused by lassa virus which is carried by rodents and is endemic in some west african countries. importation of emerging infections such as lassa fever, ebola virus disease and other viral hemorrhagic fevers into non endemic regions is a growing threat particularly as international travel and commitments in resolving conflicts in endemic countries in the west africa sub-region continue.	2015	26022703
targeting innate immunity for antiviral therapy through small molecule agonists of the rlr pathway.	the cellular response to virus infection is initiated when pathogen recognition receptors (prr) engage viral pathogen-associated molecular patterns (pamps). this process results in induction of downstream signaling pathways that activate the transcription factor interferon regulatory factor 3 (irf3). irf3 plays a critical role in antiviral immunity to drive the expression of innate immune response genes, including those encoding antiviral factors, type 1 interferon, and immune modulatory cytokin ...	2015	26676770
multiple circulating infections can mimic the early stages of viral hemorrhagic fevers and possible human exposure to filoviruses in sierra leone prior to the 2014 outbreak.	lassa fever (lf) is a severe viral hemorrhagic fever caused by lassa virus (lasv). the lf program at the kenema government hospital (kgh) in eastern sierra leone currently provides diagnostic services and clinical care for more than 500 suspected lf cases per year. nearly two-thirds of suspected lf patients presenting to the lf ward test negative for either lasv antigen or anti-lasv immunoglobulin m (igm), and therefore are considered to have a non-lassa febrile illness (nlfi). the nlfi patients ...	2015	25531344
serosurveillance of viral pathogens circulating in west africa.	sub-saharan africa is home to a variety of pathogens, but disease surveillance and the healthcare infrastructure necessary for proper management and control are severely limited. lassa virus, the cause of lassa fever, a severe hemorrhagic fever in humans is endemic in west africa. in sierra leone at the kenema government hospital lassa diagnostic laboratory, up to 70 % of acute patient samples suspected of lassa fever test negative for lassa virus infection. this large amount of acute undiagnose ...	2016	27716429
transcriptional analysis of antiviral small molecule therapeutics as agonists of the rlr pathway.	the recognition of pathogen associated molecular patterns (pamps) by pattern recognition receptors (prr) during viral infection initiates the induction of antiviral signaling pathways, including activation of the interferon regulator factor 3 (irf3). we identified small molecule compounds that activate irf3 through mavs, thereby inhibiting infection by viruses of the families flaviviridae (west nile virus, dengue virus and hepatitis c virus), filoviridae (ebola virus), orthomyxoviridae (influenz ...	2016	26981429
development of real-time reverse transcriptase qpcr assays for the detection of punta toro virus and pichinde virus.	research with high biocontainment pathogens such as rift valley fever virus (rvfv) and lassa virus (lasv) is expensive, potentially hazardous, and limited to select institutions. surrogate pathogens such as punta toro virus (ptv) for rvfv infection and pichinde virus (picv) for lasv infection allow research to be performed under more permissive bsl-2 conditions. although used as infection models, ptv and picv have no standard real-time rt-qpcr assays to detect and quantify pathogenesis. ptv is a ...	2016	27029488
murine norovirus (mnv-1) exposure in vitro to the purine nucleoside analog ribavirin increases quasispecies diversity.	ribavirin is a pharmaceutical antiviral used for the treatment of rna virus infections including norovirus, hepatitis c virus, hepatitis e virus, lassa virus, respiratory syncytial virus, and rhinovirus. despite the drug's history and documented efficacy, the antiviral mechanism of ribavirin remains unclear. mechanisms proposed include depletion of the intracellular gtp pool, immunomodulatory effects, induction of error catastrophe, inhibition of viral polymerase activity, and/or inhibition of v ...	2016	26494169
role of lamp1 binding and ph sensing by the spike complex of lassa virus.	to effectively infect cells, lassa virus needs to switch in an endosomal compartment from its primary receptor, α-dystroglycan, to a protein termed lamp1. a unique histidine triad on the surface of the receptor-binding domain from the glycoprotein spike complex of lassa virus is important for lamp1 binding. here we investigate mutated spikes that have an impaired ability to interact with lamp1 and show that although lamp1 is important for efficient infectivity, it is not required for spike-media ...	2016	27605678
lassa and ebola virus inhibitors identified using minigenome and recombinant virus reporter systems.	lassa virus (lasv) and ebola virus (ebov) infections are important global health issues resulting in significant morbidity and mortality. while several promising drug and vaccine trials for ebov are ongoing, options for lasv infection are currently limited to ribavirin treatment. a major factor impeding the development of antiviral compounds to treat these infections is the need to manipulate the virus under bsl-4 containment, limiting research to a few institutes worldwide. here we describe the ...	2016	27771389
an outbreak of ebola virus disease in the lassa fever zone.	kenema government hospital (kgh) has developed an advanced clinical and laboratory research capacity to manage the threat of lassa fever, a viral hemorrhagic fever (vhf). the 2013-2016 ebola virus (ebov) disease (evd) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of vhfs.	2016	27402779
inhibition of innate immune responses is key to pathogenesis by arenaviruses.	mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. lassa virus (lasv), for example, is endemic in several west african countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. there are currently no fda-licensed therapeutics or vaccines available to combat arenavirus infection. a hallmark ...	2016	26865707
single-vector, single-injection recombinant vesicular stomatitis virus vaccines against high-containment viruses.	there are many avenues for making an effective vaccine against viruses. depending on the virus these can include one of the following: inactivation of whole virions; attenuation of viruses; recombinant viral proteins; non-replication-competent virus particles; or surrogate virus vector systems such as vesicular stomatitis virus (vsv). vsv is a prototypic enveloped animal virus that has been used for over four decades to study virus replication, entry, and assembly due to its ability to replicate ...	2016	27076138
25-hydroxycholesterol inhibition of lassa virus infection through aberrant gp1 glycosylation.	lassa virus (lasv) infection is a major public health concern due to high fatality rates and limited effective treatment. the interferon-stimulated gene cholesterol 25-hydroxylase (ch25h) encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25hc). 25hc is involved in regulating cholesterol biosynthesis and has recently been identified as a potent antiviral targeting enveloped virus entry. here, we show a previously unrecognized role of ch25h in inhibiting lasv glycoprotein g ...	2016	27999160
aseptic meningitis caused by lassa virus: case series report.	the lassa virus is known to cause disease in different organ systems of the human body, with varying clinical manifestations. the features of severe clinical disease may include bleeding and/or central nervous system manifestations. whereas lassa fever encephalopathy and encephalitis are well described in the literature, there is paucity of data on lassa virus meningitis. we present the clinical description, laboratory diagnosis, and management of 4 consecutive cases of aseptic meningitis associ ...	2016	27957363
comparative structural and functional analysis of bunyavirus and arenavirus cap-snatching endonucleases.	segmented negative strand rna viruses of the arena-, bunya- and orthomyxovirus families uniquely carry out viral mrna transcription by the cap-snatching mechanism. this involves cleavage of host mrnas close to their capped 5' end by an endonuclease (en) domain located in the n-terminal region of the viral polymerase. we present the structure of the cap-snatching en of hantaan virus, a bunyavirus belonging to hantavirus genus. hantaan en has an active site configuration, including a metal co-ordi ...	2016	27304209
vaccine platforms to control lassa fever.	lassa virus (lasv), the most prominent human pathogen of the arenaviridae, is transmitted to humans from infected rodents and can cause lassa fever (lf). the sizeable disease burden in west africa, numerous imported lf cases worldwide, and the possibility that lasv can be used as an agent of biological warfare make a strong case for vaccine development. there are no licensed lasv vaccines and the antiviral treatment is limited to an off-label use of ribavirin that is only partially effective.	2016	27136941
structure-function relationship of the mammarenavirus envelope glycoprotein.	mammarenaviruses, including lethal pathogens such as lassa virus and junín virus, can cause severe hemorrhagic fever in humans. entry is a key step for virus infection, which starts with binding of the envelope glycoprotein (gp) to receptors on target cells and subsequent fusion of the virus with target cell membranes. the gp precursor is synthesized as a polypeptide, and maturation occurs by two cleavage events, yielding a tripartite gp complex (gpc) formed by a stable signal peptide (ssp), gp1 ...	2016	27562602
lassa fever: another threat from west africa.	lassa fever, a zoonotic viral infection, is endemic in west africa. the disease causes annual wide spread morbidity and mortality in africa, and can be imported by travelers. possible importation of lassa fever and the potential for the use of lassa virus as an agent of bioterrorism mandate clinicians in israel and other countries to be vigilant and familiar with the basic characteristics of this disease. the article reviews the basis of this infection and the clinical management of patients wit ...	2016	28265442
efficacy of favipiravir alone and in combination with ribavirin in a lethal, immunocompetent mouse model of lassa fever.	we studied the therapeutic potential of favipiravir (t-705) for lassa fever, both alone and in combination with ribavirin. favipiravir suppressed lassa virus replication in cell culture by 5 log10 units. in a novel lethal mouse model, it lowered the viremia level and the virus load in organs and normalized levels of cell-damage markers. treatment with 300 mg/kg per day, commenced 4 days after infection, when the viremia level had reached 4 log10 virus particles/ml, rescued 100% of lassa virus-in ...	2016	26531247
residues k465 and g467 within the cytoplasmic domain of gp2 play a critical role in the persistence of lymphocytic choriomeningitis virus in mice.	several arenaviruses, chiefly lassa virus (lasv), cause hemorrhagic fever disease in humans and pose serious public health concerns in their regions of endemicity. moreover, mounting evidence indicates that the worldwide-distributed prototypic arenavirus, lymphocytic choriomeningitis virus (lcmv), is a neglected human pathogen of clinical significance. we have documented that a recombinant lcmv containing the glycoprotein (gpc) gene of lasv within the backbone of the immunosuppressive clone 13 ( ...	2016	27581982
genome sequence of lassa virus isolated from the first domestically acquired case in germany.	lassa virus (lasv) is a zoonotic, hemorrhagic fever-causing virus endemic in west africa, for which no approved vaccines or specific treatment options exist. here, we report the genome sequence of lasv isolated from the first case of acquired lassa fever disease outside of africa.	2016	27660771
treatment of lassa virus infection in outbred guinea pigs with first-in-class human monoclonal antibodies.	lassa fever is a significant health threat to west african human populations with hundreds of thousands of annual cases. there are no approved medical countermeasures currently available. compassionate use of the antiviral drug ribavirin or transfusion of convalescent serum has resulted in mixed success depending on when administered or the donor source, respectively. we previously identified several recombinant human monoclonal antibodies targeting the glycoprotein of lassa virus with strong ne ...	2016	27531367
landscape determinants of fine-scale genetic structure of a small rodent in a heterogeneous landscape (hluhluwe-imfolozi park, south africa).	small mammals provide ecosystem services, acting, for example, as pollinators and seed dispersers. in addition, they are also disease reservoirs that can be detrimental to human health and they can also act as crop pests. knowledge of their dispersal preferences is therefore useful for population management and landscape planning. genetic data were used alongside landscape data to examine the influence of the landscape on the demographic connectedness of the natal multimammate mouse (mastomys na ...	2016	27406468
outbreak of lassa fever in nigeria: measures for prevention and control.		2016	27347299
small-molecule fusion inhibitors bind the ph-sensing stable signal peptide-gp2 subunit interface of the lassa virus envelope glycoprotein.	arenavirus species are responsible for severe life-threatening hemorrhagic fevers in western africa and south america. without effective antiviral therapies or vaccines, these viruses pose serious public health and biodefense concerns. chemically distinct small-molecule inhibitors of arenavirus entry have recently been identified and shown to act on the arenavirus envelope glycoprotein (gpc) to prevent membrane fusion. in the tripartite gpc complex, ph-dependent membrane fusion is triggered thro ...	2016	27194767
chimeric mice with competent hematopoietic immunity reproduce key features of severe lassa fever.	lassa fever (lasf) is a highly severe viral syndrome endemic to west african countries. despite the annual high morbidity and mortality caused by lasf, very little is known about the pathophysiology of the disease. basic research on lasf has been precluded due to the lack of relevant small animal models that reproduce the human disease. immunocompetent laboratory mice are resistant to infection with lassa virus (lasv) and, to date, only immunodeficient mice, or mice expressing human hla, have sh ...	2016	27191716
most neutralizing human monoclonal antibodies target novel epitopes requiring both lassa virus glycoprotein subunits.	lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. the epitopes of the lassa virus (lasv) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. here we have cloned 113 human monoclonal antibodies (mabs) specific for lasv glycoproteins from memory b cells of lassa fever survivors from west africa. one-half bind the gp2 fusion subunit, one-fourth recognize the gp1 receptor-binding subunit and the remaining ...	2016	27161536
lassa virus cell entry via dystroglycan involves an unusual pathway of macropinocytosis.	the pathogenic old world arenavirus lassa virus (lasv) causes a severe hemorrhagic fever with a high rate of mortality in humans. several lasv receptors, including dystroglycan (dg), tam receptor tyrosine kinases, and c-type lectins, have been identified, suggesting complex receptor use. upon receptor binding, lasv enters the host cell via an unknown clathrin- and dynamin-independent pathway that delivers the virus to late endosomes, where fusion occurs. here we investigated the mechanisms under ...	2016	27147735
new hosts of the lassa virus.	lassa virus (lasv) causes a deadly haemorrhagic fever in humans, killing several thousand people in west africa annually. for 40 years, the natal multimammate rat, mastomys natalensis, has been assumed to be the sole host of lasv. we found evidence that lasv is also hosted by other rodent species: the african wood mouse hylomyscus pamfi in nigeria, and the guinea multimammate mouse mastomys erythroleucus in both nigeria and guinea. virus strains from these animals were isolated in the bsl-4 labo ...	2016	27140942
influence of rna binding on the structure and dynamics of the lassa virus nucleoprotein.	lassa virus protects its viral genome through the formation of a ribonucleoprotein complex in which the nucleoprotein (np) encapsidates the single-stranded rna genome. crystal structures provide evidence that a conformational change must occur to allow for rna binding. in this study, the mechanism by which np binds to rna and how the conformational changes in np are achieved was investigated with molecular-dynamics simulations. np was structurally characterized in an open configuration when boun ...	2016	27028635
arenavirus diversity and phylogeography of mastomys natalensis rodents, nigeria.	mastomys natalensis rodents are natural hosts for lassa virus (lasv). detection of lasv in 2 mitochondrial phylogroups of the rodent near the niger and benue rivers in nigeria underlines the potential for lasv emergence in fresh phylogroups of this rodent. a mobala-like sequence was also detected in eastern nigeria.	2016	26982388
lassa virus seroprevalence in sibirilia commune, bougouni district, southern mali.	lassa virus (lasv) is endemic to several nations in west africa. in mali, lasv was unknown until an exported case of lassa fever was reported in 2009. since that time, rodent surveys have found evidence of lasv-infected mastomys natalensis rats in several communities in southern mali, near the border with côte d'ivoire. despite increased awareness, to date only a single case of lassa fever has been confirmed in mali. we conducted a survey to determine the prevalence of lasv exposure among person ...	2016	26981786
crystal structure of the oligomeric form of lassa virus matrix protein z.	the arenavirus matrix protein z is highly multifunctional and occurs in both monomeric and oligomeric forms. the crystal structure of a dodecamer of z from lassa virus, presented here, illustrates a ring-like structure with a highly basic center. mutagenesis demonstrates that the dimeric interface within the dodecamer and a lys-trp-lys triad at the center of the ring are important for oligomerization. this structure provides an additional template to explore the many functions of z.	2016	26912609
spatial and temporal evolution of lassa virus in the natural host population in upper guinea.	this study aimed at reconstructing the spatial and temporal evolution of lassa virus (lasv) in the natural host population. to this end, we generated 132 partial nucleoprotein sequences of lasv from m. natalensis trapped in 12 villages around faranah, upper guinea, over a period of 12 years. this study reveals two main features of lasv evolution in m. natalensis. first, the virus evolves in the reservoir with a molecular clock rate of 9 (7-11) × 10(-4) position(-1) year(-1) implying that contemp ...	2016	26911443
rat-atouille: a mixed method study to characterize rodent hunting and consumption in the context of lassa fever.	lassa fever is a zoonotic hemorrhagic illness predominant in areas across nigeria, sierra leone, guinea, liberia, and southern mali. the reservoir of lassa virus is the multimammate mouse (mastomys natalensis), a highly commensal species in west africa. primary transmission to humans occurs through direct or indirect contact with rodent body fluids such as urine, feces, saliva, or blood. our research draws together qualitative and quantitative methods to provide a fuller and more nuanced perspec ...	2016	26895631
acidic ph-induced conformations and lamp1 binding of the lassa virus glycoprotein spike.	lassa virus is an enveloped, bi-segmented rna virus and the most prevalent and fatal of all old world arenaviruses. virus entry into the host cell is mediated by a tripartite surface spike complex, which is composed of two viral glycoprotein subunits, gp1 and gp2, and the stable signal peptide. of these, gp1 binds to cellular receptors and gp2 catalyzes fusion between the viral envelope and the host cell membrane during endocytosis. the molecular structure of the spike and conformational rearran ...	2016	26849049
the high degree of sequence plasticity of the arenavirus noncoding intergenic region (igr) enables the use of a nonviral universal synthetic igr to attenuate arenaviruses.	hemorrhagic fever arenaviruses (hfas) pose important public health problems in regions where they are endemic. concerns about human-pathogenic arenaviruses are exacerbated because of the lack of fda-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. we have recently shown that the noncoding intergenic region (igr) present in each arenavirus genome segment, the s and l segments (s-igr and l-igr, res ...	2016	26739049
novel strategies for development of hemorrhagic fever arenavirus live-attenuated vaccines.	several arenaviruses, chiefly lassa virus (lasv), cause hemorrhagic fever (hf) disease in humans and pose significant public health problems in their endemic regions. moreover, hf arenaviruses represent credible biodefense threats. there are not fda-approved arenavirus vaccines and current anti-arenaviral therapy is limited to an off-label use of ribavirin that is only partially effective.	2016	27118328
mapping of the lassa virus lamp1 binding site reveals unique determinants not shared by other old world arenaviruses.	cell entry of many enveloped viruses occurs by engagement with cellular receptors, followed by internalization into endocytic compartments and ph-induced membrane fusion. a previously unnoticed step of receptor switching was found to be critical during cell entry of two devastating human pathogens: ebola and lassa viruses. our recent studies revealed the functional role of receptor switching to lamp1 for triggering membrane fusion by lassa virus and showed the involvement of conserved histidines ...	2017	28448640
molecular pathogenesis of viral hemorrhagic fever.	the clinical syndrome referred to as viral hemorrhagic fever (vhf) can be caused by several different families of rna viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. vhf is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. study of the filovirus ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenes ...	2017	28555386
human-monoclonal-antibody therapy protects nonhuman primates against advanced lassa fever.	there are no approved treatments for lassa fever, which is endemic to the same regions of west africa that were recently devastated by ebola. here we show that a combination of human monoclonal antibodies that cross-react with the glycoproteins of all four clades of lassa virus is able to rescue 100% of cynomolgus macaques when treatment is initiated at advanced stages of disease, including up to 8 d after challenge.	2017	28869611
differential immune responses to new world and old world mammalian arenaviruses.	some new world (nw) and old world (ow) mammalian arenaviruses are emerging, zoonotic viruses that can cause lethal hemorrhagic fever (hf) infections in humans. while these are closely related rna viruses, the infected hosts appear to mount different types of immune responses against them. lassa virus (lasv) infection, for example, results in suppressed immune function in progressive disease stage, whereas patients infected with junín virus (junv) develop overt pro-inflammatory cytokine productio ...	2017	28498311
interferon-γ-driven inos: a molecular pathway to terminal shock in arenavirus hemorrhagic fever.	arenaviruses such as lassa virus (lasv) cause hemorrhagic fever. terminal shock is associated with a systemic cytokine storm, but the mechanisms are ill defined. here we used hla-a2-expressing mice infected with a monkey-pathogenic strain of lymphocytic choriomeningitis virus (lcmv-we), a close relative of lasv, to investigate the pathophysiology of arenavirus hemorrhagic fever (ahf). ahf manifested as pleural effusions, edematous skin swelling, and serum albumin loss, culminating in hypovolemic ...	2017	28826838
an lasv gpc pseudotyped virus based reporter system enables evaluation of vaccines in mice under non-bsl-4 conditions.	lassa virus (lasv) causes a severe hemorrhagic fever endemic throughout western africa. because of the ability to cause lethal disease in humans, limited treatment options, and potential as a bioweapon, the need for vaccines to prevent lasv epidemic is urgent. however, lasv vaccine development has been hindered by the lack of appropriate small animal models for efficacy evaluation independent of biosafety level four (bsl-4) facilities. here we generated an lasv-glycoprotein precursor (gpc)-pseud ...	2017	28797730
temporal progression of lesions in guinea pigs infected with lassa virus.	lassa virus (lasv) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in west africa. this pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the josiah strain of lasv as well as the usefulness of strain 13 guinea pigs as an animal model for lassa fever. after experimental infection, guinea pigs ( cavia porcellus; n = 67) were serially sampled ...	2017	28438110
laboratory diagnosis of lassa fever.	lassa virus remains an important cause of illness in west africa and among the travelers returning from this region with an acute febrile illness. the symptoms of lassa fever can be nonspecific and mimic those of other endemic infections, especially early in illness, making a clinical diagnosis difficult; therefore, laboratory testing is needed to confirm the diagnosis. an early identification of lassa fever is crucial for maximizing the benefit of available antiviral therapy, as treatment effic ...	2017	28404674
dna vaccines elicit durable protective immunity against individual or simultaneous infections with lassa and ebola viruses in guinea pigs.	we previously developed optimized dna vaccines against both lassa fever and ebola hemorrhagic fever viruses and demonstrated that they were protective individually in guinea pig and nonhuman primate models. in this study, we vaccinated groups of strain 13 guinea pigs two times, four weeks apart with 50 µg of each dna vaccine or a mock vaccine at discrete sites by intradermal electroporation. five weeks following the second vaccinations, guinea pigs were exposed to lethal doses of lassa virus, eb ...	2017	29135337
a dna vaccine delivered by dermal electroporation fully protects cynomolgus macaques against lassa fever.	lassa virus (lasv) is an ambisense rna virus in the arenaviridae family and is the etiological agent of lassa fever, a severe hemorrhagic disease endemic to west and central africa. 1,2 there are no us food and drug administration (fda)-licensed vaccines available to prevent lassa fever. 1,2 in our previous studies, we developed a gene-optimized dna vaccine that encodes the glycoprotein precursor gene of lasv (josiah strain) and demonstrated that 3 vaccinations accompanied by dermal electroporat ...	2017	29045192
understanding the cryptic nature of lassa fever in west africa.	lassa fever (lf) is increasingly recognized by global health institutions as an important rodent-borne disease with severe impacts on some of west africa's poorest communities. however, our knowledge of lf ecology, epidemiology and distribution is limited, which presents barriers to both short-term disease forecasting and prediction of long-term impacts of environmental change on lassa virus (lasv) zoonotic transmission dynamics. here, we synthesize current knowledge to show that extrapolations ...	2017	28875769
structural basis for antibody-mediated neutralization of lassa virus.	the arenavirus lassa causes severe hemorrhagic fever and a significant disease burden in west africa every year. the glycoprotein, gpc, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. here we present the crystal structure of the trimeric, prefusion ectodomain of lassa gp bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. the antibody extensively anchors two monomers together at the base of the trimer ...	2017	28572385
lassa virus reverse genetics.	the old world (ow) arenavirus lassa (lasv ) is estimated to infect several hundred thousand people yearly in west africa, resulting in high numbers of lassa fever (lf), a viral hemorrhagic fever (hf) disease associated with high morbidity and mortality. to date, no licensed vaccines are available to lasv infections, and anti-lasv drug therapy is limited to an off-label use of ribavirin (rib) that is only partially effective. the development of reverse genetics has provided investigators with a n ...	2017	28508222
no measurable adverse effects of lassa, morogoro and gairo arenaviruses on their rodent reservoir host in natural conditions.	in order to optimize net transmission success, parasites are hypothesized to evolve towards causing minimal damage to their reservoir host while obtaining high shedding rates. for many parasite species however this paradigm has not been tested, and conflicting results have been found regarding the effect of arenaviruses on their rodent host species. the rodent mastomys natalensis is the natural reservoir host of several arenaviruses, including lassa virus that is known to cause lassa haemorrhagi ...	2017	28449693
mutational analysis of lassa virus glycoprotein highlights regions required for alpha-dystroglycan utilization.	lassa virus (lasv) is an enveloped rna virus endemic to west africa and responsible for severe cases of hemorrhagic fever. virus entry is mediated by the glycoprotein complex consisting of a stable-signal peptide, a receptor-binding subunit, gp1, and a viral-host membrane fusion subunit, gp2. several cellular receptors can interact with the gp1 subunit and mediate viral entry, including alpha-dystroglycan (αdg) and lysosome-associated membrane protein 1 (lamp1). in order to define the regions wi ...	2017	28679759
prevalence of lassa virus disease (lvd) in nigerian children with fever or fever and convulsions in an endemic area.	convulsions with fever in children are a common neurologic emergency in the tropics, and determining the contribution of endemic viral infections can be challenging. in particular, there is a dearth of data on the prevalence and clinical differentiation of lassa virus disease (lvd) in febrile children in endemic areas of nigeria, which has multiple lineages of the virus. the aim of this study was to determine the prevalence and presentation of lvd in febrile children with and without convulsions ...	2017	28671959
[consequences of autopsies for the living : causes of death in the clinical diagnosis "septic and toxic shock"].	there is reason to believe that the diagnosis of septic and toxic shock, as indicated on the death certificate, cannot be confirmed as the cause of death without autopsy and subsequent histological analysis. the external examination of the corpse can therefore not represent the sole basis for a reliable statement about the infection status of a corpse, e. g. as a prerequisite for embalming.	2017	28638939
evolutionary analysis of old world arenaviruses reveals a major adaptive contribution of the viral polymerase.	the old world (ow) arenavirus complex includes several species of rodent-borne viruses, some of which (i.e., lassa virus, lasv and lymphocytic choriomeningitis virus, lcmv) cause human diseases. most lcmv and lasv infections are caused by rodent-to-human transmissions. thus, viral evolution is largely determined by events that occur in the wildlife reservoirs. we used a set of human- and rodent- derived viral sequences to investigate the evolutionary history underlying ow arenavirus speciation, ...	2017	28779541
prevalence of lassa virus among rodents trapped in three south-south states of nigeria.	lassa fever has been endemic in nigeria since 1969. the rodent mastomys natalensis has been widely claimed to be the reservoir host of the lassa virus. this study was designed to investigate the dis- tribution of species of rodents in three states (edo, delta and bayelsa) of nigeria and to determine the prevalence of lassa virus amongst trapped rodents in the selected states.	2017	28748835
human antibody pieces together the puzzle of the trimeric lassa virus surface antigen.		2017	28686227
engaging market traders in lassa fever campaign: assessment of knowledge and risk behaviour.	markets provide a forum for reaching a large adult population with information on lassa fever, and therefore understanding the food handling practices of traders may provide the foundation for an effective campaign against lassa fever. this study was undertaken to provide baseline information on knowledge and food handling practices of traders in local markets in a lassa fever endemic state of nigeria.	2017	27492545
annual incidence of lassa virus infection in southern mali.	previously, we reported a high seroprevalence rate of lassa virus antibodies in inhabitants of three villages in southern mali where infected rodents have been demonstrated. herein, we report a 1-year follow-up study in which we were able to collect a second blood samples from 88.7% of participants of the same cohort. we identified 23 seroconversions for igg antibodies reactive against lassa virus, representing an incidence of 6.3% (95% confidence interval = 3.8-8.8%). seroconversion was frequen ...	2017	28093544
when viruses don't go viral: the importance of host phylogeographic structure in the spatial spread of arenaviruses.	many emerging infections are rna virus spillovers from animal reservoirs. reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. we sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent mas ...	2017	28076397
lassa virus cell entry reveals new aspects of virus-host cell interaction.	viral entry represents the first step of every viral infection and is a determinant for the host range and disease potential of a virus. here, we review the latest developments on cell entry of the highly pathogenic old world arenavirus lassa virus, providing novel insights into the complex virus-host cell interaction of this important human pathogen. we will cover new discoveries on the molecular mechanisms of receptor recognition, endocytosis, and the use of late endosomal entry factors.	2017	27928003
at home with mastomys and rattus: human-rodent interactions and potential for primary transmission of lassa virus in domestic spaces.	the multimammate mouse (mastomys natalensis) is the reservoir for lassa virus (lasv). zoonotic transmission occurs when humans are directly or indirectly exposed to fluids of the multimammate mouse, such as urine, saliva, and blood. housing characteristics and domestic organization affect rodent density in and around households and villages, and are likely to be a risk factor for lassa fever in humans where the reservoir exists. we use semi-structured interviews (n = 51), a quantitative survey ( ...	2017	28167603
a cell-based high-throughput protocol to screen entry inhibitors of highly pathogenic viruses with traditional chinese medicines.	emerging viruses such as ebola virus (ebov), lassa virus (lasv), and avian influenza virus h5n1 (aiv) are global health concerns. since there is very limited options (either vaccine or specific therapy) approved for humans against these viruses, there is an urgent need to develop prophylactic and therapeutic treatments. previously we reported a high-throughput screening (hts) protocol to identify entry inhibitors for three highly pathogenic viruses (ebov, lasv, and aiv) using a human immunodefic ...	2017	27704591