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protection of rhesus monkeys from fatal lassa fever by vaccination with a recombinant vaccinia virus containing the lassa virus glycoprotein gene.lassa fever is an acute febrile disease of west africa, where there are as many as 300,000 infections a year and an estimated 3000 deaths. as control of the rodent host is impracticable at present, the best immediate prospect is vaccination. we tested as potential vaccines in rhesus monkeys a closely related virus, mopeia virus (two monkeys), and a recombinant vaccinia virus containing the lassa virus glycoprotein gene, v-lsgpc (four monkeys). two monkeys vaccinated with the new york board of he ...19892911575
sequence analysis of the s rna of the african arenavirus mopeia: an unusual secondary structure feature in the intergenic region.mopeia virus is an apparently nonpathogenic african arenavirus which can protect animals from subsequent challenge by the closely related lassa virus. as a step toward understanding these differences in pathogenicity and the means by which mopeia virus infection can protect against subsequent lassa virus infection, cdna clones corresponding to 3419 nucleotides of mopeia virus s rna were isolated and sequenced. two open reading frames, encoding the glycoprotein precursor (gpc) and nucleocapsid (n ...19911989384
[the mopeia virus induces ph-dependent "fusion from within" in a bhk-21 cell culture].the capacity of bhk-21 cell culture to produce mopeia virus (arenaviridae family) to form syncytium upon acidification of the culture medium to ph 5.5 and lower was demonstrated. the cell fusion requires their active virus production: a virus titre in the culture medium must be at least 10(5) peu/ml. the inhibition of virus multiplication with ammonium chloride as well as treatment of the cells before the medium acidification with immune serum reduced syncytium formation markedly. no cell fusion ...19911891878
antigenic relatedness between arenaviruses defined at the epitope level by monoclonal antibodies.monoclonal antibodies (mabs) were produced against two african arenaviruses, lassa virus and mopeia virus. competitive binding analysis of mabs identified four antigenic sites on the nucleoprotein (np), two on glycoprotein 1 (gp1) and six on glycoprotein 2 (gp2) of the josiah strain of lassa virus. 64 virus isolates from western, central and southern africa were all consistently distinguishable by mabs to certain epitopic sites on gp1, gp2 and np viral proteins. furthermore, mabs to lassa virus ...19911706408
kinetic study of platelets and fibrinogen in lassa virus-infected monkeys and early pathologic events in mopeia virus-infected monkeys.the rhesus monkey, an established model of lassa fever, was used to study hematologic and hemostatic aspects of lassa fever and whether mopeia (also known as mozambique) virus induces any cellular damage in this model. six days after subcutaneous injection of 10(3.48) plaque forming units (pfu) of lassa virus (josiah strain) one group of monkeys received an intravenous injection of 111in-labeled allogeneic platelets and another group received 125i-labeled alogeneic fibrinogen. lassa virus-infect ...19854037187
lassa and mopeia virus replication in human monocytes/macrophages and in endothelial cells: different effects on il-8 and tnf-alpha gene expression.cells of the mononuclear and endothelial lineages are targets for viruses which cause hemorrhagic fevers (hf) such as the filoviruses marburg and ebola, and the arenaviruses lassa and junin. a recent model of marburg hf pathogenesis proposes that virus directly causes endothelial cell damage and macrophage release of tnf-alpha which increases the permeability of endothelial monolayers [feldmann et al. , 1996]. we show that lassa virus replicates in human monocytes/macrophages and endothelial cel ...199910534741
common antiviral cytotoxic t-lymphocyte epitope for diverse arenaviruses.members of the arenaviridae family have been isolated from mammalian hosts in disparate geographic locations, leading to their grouping as old world types (i.e., lymphocytic choriomeningitis virus [lcmv], lassa fever virus [lfv], mopeia virus, and mobala virus) and new world types (i.e., junin, machupo, tacaribe, and sabia viruses) (c. j. peters, m. j. buchmeier, p. e. rollin, and t. g. ksiazek, p. 1521-1551, in b. n. fields, d. m. knipe, and p. m. howley [ed.], fields virology, 3rd ed., 1996; p ...200111413293
human macrophages, but not dendritic cells, are activated and produce alpha/beta interferons in response to mopeia virus infection.lassa virus (lv) and mopeia virus (mv) are closely related members of the arenavirus genus, sharing 75% amino acid sequence identity. however, lv causes hemorrhagic fever in humans and nonhuman primates, whereas mv cannot induce disease. we have previously shown that antigen-presenting cells (apc)-macrophages (mp) and dendritic cells (dc)-sustain high replication rates of lv but are not activated, suggesting that they play a role in the immunosuppression observed in severe cases of lassa fever. ...200415367618
a live attenuated vaccine for lassa fever made by reassortment of lassa and mopeia viruses.lassa virus (lasv) and mopeia virus (mopv) are closely related old world arenaviruses that can exchange genomic segments (reassort) during coinfection. clone ml29, selected from a library of mopv/lasv (mop/las) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of lasv and the rna polymerase and zinc-binding protein of mopv. replication of ml29 was attenuated in guinea pigs and nonhuman primates. in murine adoptive-transfer experiments, as little as 150 pfu of ml29 induced ...200516254329
mopeia virus-related arenavirus in natal multimammate mice, morogoro, tanzania.a serosurvey involving 2,520 small mammals from tanzania identified a hot spot of arenavirus circulation in morogoro. molecular screening detected a new arenavirus in natal multimammate mice (mastomys natalensis), morogoro virus, related to mopeia virus. only a small percentage of mice carry morogoro virus, although a large proportion shows specific antibodies.200919961688
phylogeny and evolution of old world arenaviruses.the intention of this study was to investigate the genomics, phylogeny and evolution of the old world arenaviruses based on sequence data representing the four viral genes. to achieve this aim, we sequenced the complete s and l rna segments of ippy virus (ippyv), mobala virus (mobv) and mopeia virus (mopv). full-length sequences of the np, gpc, z and l genes were used to reconstruct phylogenetic relationships and to compare resulting tree topologies. each of the five old world arenavirus species ...200616494913
broad-spectrum antiviral activity of small interfering rna targeting the conserved rna termini of lassa virus.small interfering rnas targeting the conserved rna termini upstream of np and l gene were found to reduce reporter gene expression from lassa virus replicon and lassa virus mrna expression construct and to inhibit replication of different lassa virus strains, lymphocytic choriomeningitis virus, and mopeia virus in cell culture.200717371814
rt-pcr assay for detection of lassa virus and related old world arenaviruses targeting the l gene.this study describes an rt-pcr assay targeting the l rna segment of arenaviruses. conserved regions were identified in the polymerase domain of the l gene on the basis of published sequences for lassa virus, lymphocytic choriomeningitis virus (lcmv), pichinde virus and tacaribe virus, as well as 15 novel sequences for lassa virus, lcmv, ippy virus, mobala virus and mopeia virus determined in this study. using these regions as target sites, a pcr assay for detection of all known old world arenavi ...200717905372
a role for the c terminus of mopeia virus nucleoprotein in its incorporation into z protein-induced virus-like particles.arenaviruses are enveloped, negative-strand rna viruses. for several arenaviruses, virus-like particle (vlp) formation requires the viral matrix z protein. however, the mechanism by which viral ribonucleoprotein complexes are incorporated into virions is poorly understood. here, we show that the expression of the z protein and nucleoprotein (np) of mopeia virus, a close relative of the pathogenic lassa virus, resulted in the highly selective incorporation of the np protein into z protein-induced ...201020200234
presence of mopeia virus, an african arenavirus, related to biotope and individual rodent host characteristics: implications for virus transmission.abstract the east african mopeia virus (mopv) is an arenavirus closely related to the highly pathogenic west african lassa virus, even sharing the same reservoir rodent host mastomys natalensis. because mopv is not known to cause human disease, it offers a unique alternative for studying lassa virus transmission. we investigated how habitat, population density, and host characteristics are related to mopv occurrence in m. natalensis populations in morogoro, tanzania. in 3 contrasting habitats, 5 ...201021142956
alix/aip1 is required for np incorporation into mopeia virus z-induced virus-like particles.during virus particle assembly, the arenavirus nucleoprotein (np) associates with the viral genome to form nucleocapsids, which ultimately become incorporated into new virions at the cell membrane. virion release is facilitated by the viral matrix z protein through its interaction with the cellular endosomal sorting complex required for transport (escrt) machinery. however, the mechanism of nucleocapsid incorporation into virions is not well understood. here, we demonstrate that alix/aip1, an es ...201121248028
novel arenavirus sequences in hylomyscus sp. and mus (nannomys) setulosus from c+¦te d'ivoire: implications for evolution of arenaviruses in africa.this study aimed to identify new arenaviruses and gather insights in the evolution of arenaviruses in africa. during 2003 through 2005, 1,228 small mammals representing 14 different genera were trapped in 9 villages in south, east, and middle west of c+¦te d'ivoire. specimens were screened by pan-old world arenavirus rt-pcrs targeting s and l rna segments as well as immunofluorescence assay. sequences of two novel tentative species of the family arenaviridae, menekre and gbagroube virus, were de ...201121695269
human dendritic cells infected with the non-pathogenic mopeia virus induce stronger t-cell responses than with lassa virus.events leading to death in severe cases of lassa fever (lf) are unknown. fatality seems to be linked to high viremia and immunosuppression, with cellular immunity, rather than neutralizing antibodies, appearing to be essential for survival. we previously compared lassa virus (lv) with its genetically close but non pathogenic homolog mopeia virus (mv), which was used to model non fatal lf. we showed that strong and early activation of antigen-presenting cells (apc) may play a crucial role in cont ...201121632749
cross-species analysis of the replication complex of old world arenaviruses reveals two nucleoprotein sites involved in l protein function.lassa virus (lasv) causing hemorrhagic lassa fever in west africa, mopeia virus (mopv) from east africa, and lymphocytic choriomeningitis virus (lcmv) are the main representatives of the old world arenaviruses. little is known about how the components of the arenavirus replication machinery, i.e., the genome, nucleoprotein (np), and l protein, interact. in addition, it is unknown whether these components can function across species boundaries. we established minireplicon systems for mopv and lcm ...201121917982
evaluation of lassa virus vaccine immunogenicity in a cba/j-ml29 mouse model.lassa fever (lf) is one of the most prevalent viral hemorrhagic fevers in west africa responsible for thousands of deaths annually. the bsl-4 containment requirement and lack of small animal model to evaluate lassa virus (lasv)-specific cell-mediated immunity (cmi) complicate development of effective lf vaccines. here we have described a cba/j-ml29 model allowing evaluation of lasv-specific cmi responses in mice. this model is based on mopeia virus reassortant clone ml29, an attractive immunogen ...201222234266
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 ...201526401045
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 ...201222585682
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 ...201222532679
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 ...201324069471
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 ...201323041432
vaccines inducing immunity to lassa virus glycoprotein and nucleoprotein protect macaques after a single shot.lassa fever is a major threat in western africa. the large number of people living at risk for this disease calls for the development of a vaccine against lassa virus (lasv). we generated live-attenuated lasv vaccines based on measles virus and mopeia virus platforms and expressing different lasv antigens, with the aim to develop a vaccine able to protect after a single shot. we compared the efficacy of these vaccines against lasv in cynomolgus monkeys. the vaccines were well tolerated and prote ...201931578242
lassa virus vaccine candidate ml29 generates truncated viral rnas which contribute to interfering activity and attenuation.defective interfering particles (dips) are naturally occurring products during virus replication in infected cells. dips contain defective viral genomes (dvgs) and interfere with replication and propagation of their corresponding standard viral genomes by competing for viral and cellular resources, as well as promoting innate immune antiviral responses. consequently, for many different viruses, including mammarenaviruses, dips play key roles in the outcome of infection. due to their ability to b ...202133573250
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 ...201424421914
activity inhibition and crystal polymorphism induced by active-site metal swapping.the arenaviridae family is one of the two rna viral families that encode a 3'-5' exonuclease in their genome. an exonuclease domain is found in the arenaviridae nucleoprotein and targets dsrna specifically. this domain is directly involved in suppression of innate immunity in the host cell. like most phosphate-processing enzymes, it requires a divalent metal ion such as mg(2+) (or mn(2+)) as a cofactor to catalyse nucleotide-cleavage and nucleotide-transfer reactions. on the other hand, calcium ...201728777079
activation of the rlr/mavs signaling pathway by the l protein of mopeia virus.the family arenaviridae includes several important human pathogens that can cause severe hemorrhagic fever and greatly threaten public health. as a major component of the innate immune system, the rlr/mavs signaling pathway is involved in recognizing viral components and initiating antiviral activity. it has been reported that arenavirus infection can suppress the innate immune response, and np and z proteins of pathogenic arenaviruses can disrupt rlr/mavs signaling, thus inhibiting production o ...201627605671
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