| 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 |
| 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 |
| immune evasion mechanisms of arenaviruses. | | 2015 | 26595677 |
| 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 |
| 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 |
| 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 |
| 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 |
| lassa virus in multimammate rats, côte d'ivoire, 2013. | | 2015 | 26196447 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| the rubber plantation environment and lassa fever epidemics in liberia, 2008-2012: a spatial regression. | as lassa fever continues to be a public health challenge in west africa, it is critical to produce good maps of its risk pattern for use in active surveillance and control intervention. we identified eight spatial features related to the rubber plantation environment and used them as explanatory variables for lassa fever (lf) outbreaks on the uniroyal liberian agricultural company (lac) rubber plantation environment in grand bassa county, liberia. we computed classical and spatial lag regression ... | 2014 | 25457605 |
| clinical features and patient management of lujo hemorrhagic fever. | in 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, lujo virus, occurred in johannesburg, south africa. lujo virus is only the second pathogenic arenavirus, after lassa virus, to be recognized in africa and the first in over 40 years. because of the remote, resource-poor, and often politically unstable regions where lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their c ... | 2014 | 25393244 |
| lassa and marburg viruses elicit distinct host transcriptional responses early after infection. | lassa virus and marburg virus are two causative agents of viral hemorrhagic fever. their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. using the transcriptional response of the host during infection can lead to ... | 2014 | 25377889 |
| 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 |
| exonuclease domain of the lassa virus nucleoprotein is critical to avoid rig-i signaling and to inhibit the innate immune response. | lassa virus (lasv), which causes a viral hemorrhagic fever, inhibits the innate immune response. the exonuclease (exon) domain of its nucleoprotein (np) is implicated in the suppression of retinoic acid-inducible gene i (rig-i) signaling. we show here that a lasv in which exon function has been abolished strongly activates innate immunity and that this effect is dependent on rig-i signaling. these results highlight the key role of np exon function in the immune evasion that occurs during lasv in ... | 2014 | 25253344 |
| the exonuclease domain of lassa virus nucleoprotein is involved in antigen-presenting-cell-mediated nk cell responses. | lassa virus is an old world arenavirus which causes lassa hemorrhagic fever in humans, mostly in west africa. lassa fever is an important public health problem, and a safe and effective vaccine is urgently needed. the infection causes immunosuppression, probably due to the absence of activation of antigen-presenting cells (dendritic cells and macrophages), low type i interferon (ifn) production, and deficient nk cell function. however, a recombinant lassa virus carrying d389a and g392a substitut ... | 2014 | 25253342 |
| lassa serology in natural populations of rodents and horizontal transmission. | lassa virus causes hemorrhagic fever in west africa. previously, we demonstrated by pcr screening that only the multimammate mouse, mastomys natalensis, hosts lassa virus in guinea. in the present study, we used the same specimen collection from 17 villages in coastal, upper, and forest guinea to investigate the lassa virus serology in the rodent population. the aim was to determine the dynamics of antibody development in m. natalensis and to detect potential spillover infections in other rodent ... | 2014 | 25229705 |
| mapping transmission risk of lassa fever in west africa: the importance of quality control, sampling bias, and error weighting. | lassa fever is a disease that has been reported from sites across west africa; it is caused by an arenavirus that is hosted by the rodent m. natalensis. although it is confined to west africa, and has been documented in detail in some well-studied areas, the details of the distribution of risk of lassa virus infection remain poorly known at the level of the broader region. in this paper, we explored the effects of certainty of diagnosis, oversampling in well-studied region, and error balance on ... | 2014 | 25105746 |
| virus entry. lassa virus entry requires a trigger-induced receptor switch. | lassa virus spreads from a rodent to humans and can lead to lethal hemorrhagic fever. despite its broad tropism, chicken cells were reported 30 years ago to resist infection. we found that lassa virus readily engaged its cell-surface receptor α-dystroglycan in avian cells, but virus entry in susceptible species involved a ph-dependent switch to an intracellular receptor, the lysosome-resident protein lamp1. iterative haploid screens revealed that the sialyltransferase st3gal4 was required for th ... | 2014 | 24970085 |
| segmented negative-strand rna viruses and rig-i: divide (your genome) and rule. | the group of negative-stranded rna viruses (nsvs) with a segmented genome comprises pathogens like influenza virus (eight segments), rift valley fever virus and hantavirus (three segments), or lassa virus (two segments). partitioning the genome allows rapid evolution of new strains by reassortment. each segment carries a short double-stranded (ds) 'panhandle' structure which serves as promoter. similar dsrna structures, however, represent the optimal ligand for rig-i, a cytoplasmic pathogen sens ... | 2014 | 24930021 |
| evolution of recombinant lymphocytic choriomeningitis virus/lassa virus in vivo highlights the importance of the gpc cytosolic tail in viral fitness. | a key characteristic of arenaviruses is their ability to establish persistent infection in their natural host. different factors like host age, viral dose strain, and route of infection may contribute to the establishment of persistence. however, the molecular mechanisms governing persistence are not fully understood. here, we describe gain-of-function mutations of lymphocytic choriomeningitis virus (lcmv) expressing lassa virus (lasv) gp, which can prolong viremia in mice depending on the seque ... | 2014 | 24829355 |
| role of the c terminus of lassa virus l protein in viral mrna synthesis. | the n terminus of arenavirus l protein contains an endonuclease presumably involved in "cap snatching." here, we employed the lassa virus replicon system to map other l protein sites that might be involved in this mechanism. residues phe-1979, arg-2018, phe-2071, asp-2106, trp-2173, tyr-2179, arg-2200, and arg-2204 were important for viral mrna synthesis but dispensable for genome replication. thus, the c terminus of l protein is involved in the mrna synthesis process, potentially by mediating c ... | 2014 | 24829349 |
| 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 |
| 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 |
| geographic distribution and genetic characterization of lassa virus in sub-saharan mali. | lassa fever is an acute viral illness characterized by multi-organ failure and hemorrhagic manifestations. lassa fever is most frequently diagnosed in nigeria, sierra leone, liberia, and guinea, although sporadic cases have been recorded in other west african countries, including mali. the etiological agent of lassa fever is lassa virus (lasv), an arenavirus which is maintained in nature and frequently transmitted to humans by mastomys natalensis. the purpose of this study was to better define t ... | 2013 | 24340119 |
| 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 |
| two novel arenaviruses detected in pygmy mice, ghana. | two arenaviruses were detected in pygmy mice (mus spp.) by screening 764 small mammals in ghana. the natal multimammate mouse (mastomys natalensis), the known lassa virus reservoir, was the dominant indoor rodent species in 4 of 10 sites, and accounted for 27% of all captured rodents. no rodent captured indoors tested positive for an arenavirus. | 2013 | 24188212 |
| transcriptome analysis of human peripheral blood mononuclear cells exposed to lassa virus and to the attenuated mopeia/lassa reassortant 29 (ml29), a vaccine candidate. | lassa virus (lasv) is the causative agent of lassa fever and is responsible for several hundred thousand infections and thousands of deaths annually in west africa. lasv and the non-pathogenic mopeia virus (mopv) are both rodent-borne african arenaviruses. a live attenuated reassortant of mopv and lasv, designated ml29, protects rodents and primates from lasv challenge and appears to be more attenuated than mopv. to gain better insight into lasv-induced pathology and mechanism of attenuation we ... | 2013 | 24069471 |
| lead optimization of an acylhydrazone scaffold possessing antiviral activity against lassa virus. | previously we reported the optimization of antiviral scaffolds containing benzimidazole and related heterocycles possessing activity against a variety of arenaviruses. these series of compounds were discovered through an hts campaign of a 400,000 small molecule library using lentivirus-based pseudotypes incorporated with the lassa virus envelope glycoprotein (lasv gp). this screening also uncovered an alternate series of very potent arenavirus inhibitors based upon an acylhydrazone scaffold. sub ... | 2013 | 24064500 |
| infection of type i interferon receptor-deficient mice with various old world arenaviruses: a model for studying virulence and host species barriers. | lassa virus causes hemorrhagic lassa fever in humans, while the related old world arenaviruses mopeia, morogoro, and mobala are supposedly apathogenic to humans and cause only inapparent infection in non-human primates. here, we studied whether the virulence of old world arenaviruses in humans and non-human primates is reflected in type i interferon receptor deficient (ifnar(-/-)) mice by testing several strains of lassa virus vs. the apathogenic viruses mopeia, morogoro, and mobala. all lassa v ... | 2013 | 23991083 |
| mice lacking functional stat1 are highly susceptible to lethal infection with lassa virus. | lassa fever (lf) is a potentially lethal human disease that is caused by the arenavirus lassa virus (lasv). annually, around 300,000 infections with up to 10,000 deaths occur in regions of lassa fever endemicity in west africa. here we demonstrate that mice lacking a functional stat1 pathway are highly susceptible to infection with lasv and develop lethal disease with pathology similar to that reported in humans. | 2013 | 23903830 |
| pathogenesis of lassa fever virus infection: i. susceptibility of mice to recombinant lassa gp/lcmv chimeric virus. | lassa virus (lasv) is a bsl-4 restricted agent. to allow study of infection by lasv under bsl-2 conditions, we generated a recombinant virus in which the lasv glycoprotein (gp) was placed on the backbone of lymphocytic choriomeningitis virus (lcmv) cl13 nucleoprotein, z and polymerase genes (rlcmv cl13/lasv gp). the recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. inoculation of immunocompetent adults resulted in an acute infection, generation ... | 2013 | 23684417 |
| transcriptional profiling of the circulating immune response to lassa virus in an aerosol model of exposure. | lassa virus (lasv) is a significant human pathogen that is endemic to several countries in west africa. infection with lasv leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. little is known about the complex immune mechanisms governing the response to lasv or the genetic determinants of susceptibility and resistance to infection. in the study presented here, we have used a whole-genome, microarray-ba ... | 2013 | 23638192 |
| structures of arenaviral nucleoproteins with triphosphate dsrna reveal a unique mechanism of immune suppression. | a hallmark of severe lassa fever is the generalized immune suppression, the mechanism of which is poorly understood. lassa virus (lasv) nucleoprotein (np) is the only known 3'-5' exoribonuclease that can suppress type i interferon (ifn) production possibly by degrading immune-stimulatory rnas. how this unique enzymatic activity of lasv np recognizes and processes rna substrates is unknown. we provide an atomic view of a catalytically active exoribonuclease domain of lasv np (lasv np-c) in the pr ... | 2013 | 23615902 |
| the role of oligomerization for the biological functions of the arenavirus nucleoprotein. | the lassa virus nucleoprotein (np) is a multifunctional protein that plays an essential role in many aspects of the viral life cycle, including rna encapsidation, viral transcription and replication, recruitment of ribonucleoprotein complexes to viral budding sites, and inhibition of the host cell interferon response. while it is known that np is capable of forming oligomers, both the oligomeric state of np in mammalian cells and the significance of np oligomerization for its various functions r ... | 2013 | 23553456 |
| identification of virulence determinants within the l genomic segment of the pichinde arenavirus. | several arenaviruses are responsible for causing viral hemorrhagic fevers (vhf) in humans. lassa virus (lasv), the causative agent of lassa fever, is a biosafety level 4 (bsl4) pathogen that requires handling in bsl4 facilities. in contrast, the pichinde arenavirus (picv) is a bsl2 pathogen that can cause hemorrhagic fever-like symptoms in guinea pigs that resemble those observed in human lassa fever. comparative sequence analysis of the avirulent p2 strain of picv and the virulent p18 strain sh ... | 2013 | 23552411 |
| differential recognition of old world and new world arenavirus envelope glycoproteins by subtilisin kexin isozyme 1 (ski-1)/site 1 protease (s1p). | the arenaviruses are an important family of emerging viruses that includes several causative agents of severe hemorrhagic fevers in humans that represent serious public health problems. a crucial step of the arenavirus life cycle is maturation of the envelope glycoprotein precursor (gpc) by the cellular subtilisin kexin isozyme 1 (ski-1)/site 1 protease (s1p). comparison of the currently known sequences of arenavirus gpcs revealed the presence of a highly conserved aromatic residue at position p ... | 2013 | 23536681 |
| deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry. | glycosylated α-dystroglycan (α-dg) serves as cellular entry receptor for multiple pathogens, and defects in its glycosylation cause hereditary walker-warburg syndrome (wws). at least eight proteins are critical to glycosylate α-dg, but many genes mutated in wws remain unknown. to identify modifiers of α-dg, we performed a haploid screen for lassa virus entry, a hemorrhagic fever virus causing thousands of deaths annually that hijacks glycosylated α-dg to enter cells. in complementary screens, we ... | 2013 | 23519211 |
| a historical look at the first reported cases of lassa fever: igg antibodies 40 years after acute infection. | lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in west africa. one important question regarding lassa fever is the duration of immunoglobulin g (igg) antibody after infection. we were able to locate three persons who worked in nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of lassa fever in the late 1960s, including the person from whom lassa virus was first isolated. two persons had high titers of ... | 2013 | 23390223 |
| a recently isolated lassa virus from mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques. | the virulence of soromba-r, a lassa virus strain recently isolated from southern mali, was assessed in 2 animal models of lassa fever: inbred strain 13 guinea pigs and cynomolgus macaques. in both models, the malian isolate demonstrated tissue tropism and viral titers similar to those of historical lassa virus isolates from sierra leone (josiah) and liberia (z-132); however, the soromba-r isolate was found to be less pathogenic, as determined by decreased mortality and prolonged time to euthanas ... | 2013 | 23303805 |
| housing equity for health equity: a rights-based approach to the control of lassa fever in post-war sierra leone. | poor quality housing is an infringement on the rights of all humans to a standard of living adequate for health. among the many vulnerabilities of those without adequate shelter is the risk of disease spread by rodents and other pests. one such disease is lassa fever, an acute and sometimes severe viral hemorrhagic illness endemic in west africa. lassa virus is maintained in the rodent mastomys natalensis, commonly known as the "multimammate rat," which frequently invades the domestic environmen ... | 2013 | 23282054 |
| the microtubule motor protein kif13a is involved in intracellular trafficking of the lassa virus matrix protein z. | the small matrix protein z of arenaviruses has been identified as the main driving force to promote viral particle production at the plasma membrane. although multiple functions of z in the arenaviral life cycle have been uncovered, the mechanism of intracellular transport of z to the site of virus budding is poorly understood and cellular motor proteins that mediate z trafficking remain to be identified. in the present study, we report that the z protein of the old world arenavirus lassa virus ... | 2013 | 23279019 |
| targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever. | a number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. lassa virus, found in west africa, causes severe hemorrhagic fever (hf), while the other principal old world arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. the new world agents, including junin, machupo and sabia virus, are highly pathogenic for humans. arenaviral hf is characterized ... | 2013 | 23261843 |
| the role of proteolytic processing and the stable signal peptide in expression of the old world arenavirus envelope glycoprotein ectodomain. | maturation of the arenavirus gp precursor (gpc) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (ski-1)/site 1 protease (s1p), yielding a tripartite complex comprised of a stable signal peptide (ssp), the receptor-binding gp1, and the fusion-active transmembrane gp2. here we investigated the roles of ski-1/s1p processing and ssp in the biosynthesis of the recombinant gp ectodomains of lymphocytic choriomeningitis virus (lcmv) ... | 2013 | 23218200 |
| immune responses and lassa virus infection. | lassa fever is a hemorrhagic fever endemic to west africa and caused by lassa virus, an old world arenavirus. it may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. the immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immu ... | 2012 | 23202504 |
| pathogenesis of lassa fever. | lassa virus, an old world arenavirus (family arenaviridae), is the etiological agent of lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of west africa with mortality rates for hospitalized patients varying between 5-10%. currently, there are no approved vaccines against lassa fever for use in humans. here, we review the published literature on the life cycle of lassa virus with the specific focus put on lassa fever pathogenesis i ... | 2012 | 23202452 |
| density thresholds for mopeia virus invasion and persistence in its host mastomys natalensis. | well-established theoretical models predict host density thresholds for invasion and persistence of parasites with a density-dependent transmission. studying such thresholds in reality, however, is not obvious because it requires long-term data for several fluctuating populations of different size. we developed a spatially explicit and individual-based seir model of mopeia virus in multimammate mice mastomys natalensis. this is an interesting model system for studying abundance thresholds becaus ... | 2013 | 23041432 |
| molecular diagnostics for lassa fever at irrua specialist teaching hospital, nigeria: lessons learnt from two years of laboratory operation. | lassa fever is a viral hemorrhagic fever endemic in west africa. however, none of the hospitals in the endemic areas of nigeria has the capacity to perform lassa virus diagnostics. case identification and management solely relies on non-specific clinical criteria. the irrua specialist teaching hospital (isth) in the central senatorial district of edo state struggled with this challenge for many years. | 2012 | 23029594 |
| structural basis for the dsrna specificity of the lassa virus np exonuclease. | lassa virus causes hemorrhagic fever characterized by immunosuppression. the nucleoprotein of lassa virus, termed np, binds the viral genome. it also has an additional enzymatic activity as an exonuclease that specifically digests double-stranded rna (dsrna). dsrna is a strong signal to the innate immune system of viral infection. digestion of dsrna by the np exonuclease activity appears to cause suppression of innate immune signaling in the infected cell. although the fold of the np enzyme is c ... | 2012 | 22937163 |
| studies on the binding modes of lassa nucleoprotein complexed with m7gpppg and dttp by molecular dynamic simulations and free energy calculations. | lassa virus can cause dreadful human hemorrhagic disease, for which there is no effective therapy. a recent study points out that the amino (n)-terminal domain of lassa virus nucleoprotein (np) plays an important role in viral rna synthesis and firstly solved the x-ray crystal structures of np complexed with the capped deoxythymidine triphosphate (dttp) analog, but the binding mode of m7gpppg to the n domain of np, which is required for viral rna transcription, has not been studied. in this stud ... | 2013 | 22871039 |
| plasmacytoid dendritic cells are productively infected and activated through tlr-7 early after arenavirus infection. | the antiviral response is largely mediated by dendritic cells (dcs), including conventional (c) dcs that function as antigen-presenting cells, and plasmacytoid (p) dcs that produce type i interferons, making them an attractive target for viruses. we find that the old world arenaviruses lymphocytic choriomeningitis virus clone 13 (lcmv cl13) and lassa virus bind pdcs to a greater extent than cdcs. consistently, lcmv cl13 targets pdcs early after in vivo infection of its natural murine host and es ... | 2012 | 22704622 |
| cell surface molecules involved in infection mediated by lymphocytic choriomeningitis virus glycoprotein. | the glycoprotein (gp) of lymphocytic choriomeningitis virus (lcmv), the prototype arenavirus, is a promising envelope protein of lentiviral pseudotype vectors for gene therapy. the distribution of dystroglycan, a known receptor for lcmv, cannot explain the narrow tropism of lcmv-gp-pseudotypes. here, we examined whether infection of lcmv-gp-pseudotypes was affected by the expression of four cell surface molecules-axl and tyro3 (from the tam family) and dc-sign and lsectin (from the c-type lectin ... | 2012 | 22673088 |
| the impact of human conflict on the genetics of mastomys natalensis and lassa virus in west africa. | environmental changes have been shown to play an important role in the emergence of new human diseases of zoonotic origin. the contribution of social factors to their spread, especially conflicts followed by mass movement of populations, has not been extensively investigated. here we reveal the effects of civil war on the phylogeography of a zoonotic emerging infectious disease by concomitantly studying the population structure, evolution and demography of lassa virus and its natural reservoir, ... | 2012 | 22615894 |
| hospital-based surveillance for lassa fever in edo state, nigeria, 2005-2008. | to estimate the burden of lassa fever in northern and central edo, a state in south nigeria where lassa fever has been reported. | 2012 | 22594713 |
| nk cells are strongly activated by lassa and mopeia virus-infected human macrophages in vitro but do not mediate virus suppression. | lassa virus (lasv) and mopeia virus (mopv) are closely related arenaviruses. lasv causes hemorrhagic fever, whereas mopv is not pathogenic. both viruses display tropism for apcs such as dcs and macrophages. during viral infections, nk cells are involved in the clearance of infected cells and promote optimal immune responses by interacting with apcs. we used an in vitro model of human nk and apc coculture to study the role of nk cells and to characterize their interactions with apcs during lasv a ... | 2012 | 22585682 |
| rapid and specific detection of lassa virus by reverse transcription-pcr coupled with oligonucleotide array hybridization. | to facilitate sequence-specific detection of dna amplified in a diagnostic reverse transcription (rt)-pcr for lassa virus, we developed an array featuring 47 oligonucleotide probes for post-pcr hybridization of the amplicons. the array procedure may be performed with low-tech equipment and does not take longer than agarose gel detection. | 2012 | 22535985 |
| pathogenic old world arenaviruses inhibit tlr2/mal-dependent proinflammatory cytokines in vitro. | lymphocytic choriomeningitis virus (lcmv), the prototype arenavirus, and lassa virus (lasv), the causative agent of lassa fever (lf), have extensive strain diversity and significant variations in pathogenicity for humans and experimental animals. the we strain of lcmv (lcmv-we), but not the armstrong (arm) strain, induces a fatal lf-like disease in rhesus macaques. we also demonstrated that lasv infection of human macrophages and endothelial cells resulted in reduced levels of proinflammatory cy ... | 2012 | 22532679 |
| binding of lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan. | the arenavirus lassa virus (lasv) causes a severe haemorrhagic fever with high mortality in man. the cellular receptor for lasv is dystroglycan (dg). dg is a ubiquitous receptor for extracellular matrix (ecm) proteins, which cooperates with β1 integrins to control cell-matrix interactions. here, we investigated whether lasv binding to dg triggers signal transduction, mimicking the natural ligands. engagement of dg by lasv resulted in the recruitment of the adaptor protein grb2 and the protein ki ... | 2012 | 22405130 |
| molecular characterization of the processing of arenavirus envelope glycoprotein precursors by subtilisin kexin isozyme-1/site-1 protease. | a crucial step in the life cycle of arenaviruses is the biosynthesis of the mature fusion-active viral envelope glycoprotein (gp) that is essential for virus-host cell attachment and entry. the maturation of the arenavirus gp precursor (gpc) critically depends on proteolytic processing by the cellular proprotein convertase (pc) subtilisin kexin isozyme-1 (ski-1)/site-1 protease (s1p). here we undertook a molecular characterization of the ski-1/s1p processing of the gpcs of the prototypic arenavi ... | 2012 | 22357276 |
| genome-wide scans provide evidence for positive selection of genes implicated in lassa fever. | rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. with the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. based on this approach, we have previously hypothesized that lassa virus (lasv) may have been a driver of natural selecti ... | 2012 | 22312054 |
| self-association of lymphocytic choriomeningitis virus nucleoprotein is mediated by its n-terminal region and is not required for its anti-interferon function. | arenaviruses have a bisegmented, negative-strand rna genome. both the large (l) and small (s) genome segments use an ambisense coding strategy to direct the synthesis of two viral proteins. the l segment encodes the virus polymerase (l protein) and the matrix z protein, whereas the s segment encodes the nucleoprotein (np) and the glycoprotein precursor (gpc). nps are the most abundant viral protein in infected cells and virions and encapsidate genomic rna species to form an np-rna complex that, ... | 2012 | 22258244 |
| [arenavirus infections]. | arenaviruses are the collective name for viruses, which belong to the family arenaviridae. they replicate in the cytoplasm of cells, and were named after the sandy (latin, arenosus) appearance of the ribosomes often seen in thin sections of virions under electron microscope. several arenaviruses, such as lassa virus in west africa, and junin, guanarito, sabia, machupo, and chapare viruses in south america, cause sever viral hemorrhagic fevers (vhf) in humans and represent a serious public health ... | 2012 | 24153233 |
| 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 |
| 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 |
| viral haemorrhagic fevers imported into non-endemic countries: risk assessment and management. | viral haemorrhagic fevers (vhfs) are severe infections capable of causing haemorrhagic disease and fatal multi-organ failure. crimean-congo, marburg, ebola and lassa viruses cause both sporadic cases and large epidemics over wide endemic areas. | 2010 | 20682627 |
| fibroblastic reticular cells and their role in viral hemorrhagic fevers. | viral hemorrhagic fevers (vhfs) caused by ebola, marburg and lassa viruses often manifest as multiple organ dysfunction and hemorrhagic shock with high mortality. these viruses target numerous cell types, including monocytes and dendritic cells, which are primary early targets that mediate critical pathogenetic processes. this review focuses on fibroblastic reticular cells (frcs), another prevalent infected cell type that is known as a key regulator of circulatory and immune functions. viral inf ... | 2009 | 19400762 |
| 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 |
| [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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |