Publications

TitleAbstractYear
Filter
PMID
Filter
pathology of bolivian hemorrhagic fever in the african green monkey.gross and microscopic pathological findings are presented for an african green monkey model of fatal bolivian hemorrhagic fever. six animals were inoculated with 1,000 plaque-forming units of machupo virus, the etiological agent of bolivian hemorrhagic fever. five of the monkeys died within 13 days with signs of fever, anorexia, shock, and hemorrhage. the sixth monkey survived until the 24th day and died with signs of central nervous system disease. gross lesions in the five monkeys that die in ...197899059
studies of the coagulation system and blood pressure during experimental bolivian hemorrhagic fever in rhesus monkeys.experimental infection of rhesus monkeys (macaca mulatta) with machupo virus produced a hemorrhagic disease similar to that of bolivian hemorrhagic fever in humans. the disease in infected animals was also characterized by the development of hypotension and coagulation abnormalities as indicated by severe thrombocytopenia and prolongation of the activated partial thromboplastin time. evidence for disseminated intravascular coagulation was inconclusive due to the presence of normal to elevated fi ...1978103447
a rhesus monkey model for the study of bolivian hemorrhagic fever.two groups of rhesus monkeys were inoculated with either 10(5) (group 1) or 10(3) (group 2) plaque-forming units of machupo virus, the etiologic virus of bolivian hemorrhagic fever. the monkeys were observed for clinical signs; body temperatures, viremias, hematologic changes, and virus-neutralizing antibody were measured. the onset of clinical signs for groups 1 and 2 occurred on days 4-6 and 7-10, respectively, with fever, anorexia, and depression. these and other signs became more severe, and ...1976173762
pathology of chronic bolivian hemorrhagic fever in the rhesus monkey.gross and microscopic lesions of bolivian hemorrhagic fever (bhf) are described in 10 rhesus monkeys that survived from 30 to 78 days after subcutaneous inoculation with a dose of 10(3) plaque-forming units (pfu) of machupo virus, a dose which produces a severe and generally fatal disease. six of the monkeys had been given low doses of homologous immune globulin when initial signs of infection appeared. monkeys exhibited clinical signs in two phases. the initial signs of acute infection which be ...1976181994
infection of wild and laboratory animals with machupo and latino viruses.natural infection with machupo and latino viruses occurs only in the cricetine rodent calomys callosus. machupo virus induces fatal infection in suckling mice and hamsters, and in adult guinea-pigs, marmosets, and rhesus monkeys. latino virus kills only suckling hamsters; it produces chronic but non-viraemic infection in calomys rodents.machupo virus, in contrast, induces a viraemic immunotolerant infection in suckling calomys, and a split response in animals more than 9 days of age. tolerant in ...1975182399
pathogenesis of machupo virus infection in primates.experimental machupo virus infection of rhesus and cynomolgus monkeys produced a severe illness consisting of an initial clinical phase and a later neurological phase. cumulative mortality during the two phases was 80% and 95% respectively. attempts to alter the pathogenesis with decomplementation or immunosuppression resulted in earlier deaths of the monkeys.1975182402
rodent control programmes in areas affected by bolivian haemorrhagic fever.bolivian haemorrhagic fever (bhf) caused by machupo virus is acquired by contact with the excretions and secretions of calomys callosus, an indigenous cricetine rodent which is preadapted to peridomestic habitats. it competes successfully with mus musculus, but not with rattus rattus. a successful disease control programme has functioned in beni department since 1964. it is based on trapping surveys and the detection of splenomegaly in calomys rodents as an index of chronic virus infection. mass ...1975182405
protection of monkeys against machupo virus by the passive administration of bolivian haemorrhagic fever immunoglobulin (human origin).bolivian haemorrhagic fever immunoglobulin of human origin, given either prior to or shortly after experimental infection with machupo virus, protected rhesus and cynomolgus monkeys against initial clinical illness. some survivors developed severe neurological signs 30-47 days after virus inoculation and died 4-6 days later. results from one of the experiments suggested that the development of neurological signs was associated more frequently with high doses of immunoglobulin than with intermedi ...1975182406
status of arenavirus vaccines and their application.a limited but definite need exists for vaccines against lassa, junin, and machupo viruses. medical and laboratory personnel, as well as defined high-risk population groups, require protection from these highly virulent agents. to date little work has been done on inactivated vaccines for these viruses. a live attenuated junin vaccine has been tested successfully in more than 600 persons, and a high-passage machupo virus strain has protected rhesus monkeys against lethal infection produced by a h ...1975182407
structural polypeptides of machupo virus.the structural proteins of an arenavirus pathogen, machupo virus, were compared to the structural proteins of two previously characterized non-pathogenic arenaviruses, pichinde and tacaribe, in sds-polyacrylamide gels. similarities in mol. wt. of the major structural proteins from both pathogenic and non-pathogenic viruses were apparent; however, some differences in the number of glycosylation properties of minor proteins were observed. machupo virions contain two major protein species. the most ...1978212518
viral haemorrhagic fevers of man.this article reviews the current state of knowledge on the viral haemorrhagic fevers that infect man, namely smallpox, chikungunya fever, dengue fever, rift valley fever, yellow fever, crimean haemorrhagic fever, kyasanur forest disease, omsk haemorrhagic fever, argentinian haemorrhagic fever (junin virus), bolivian haemorrhagic fever (machupo virus), lassa fever, haemorrhagic fever with renal syndrome, and marburg and ebola virus diseases.1978310725
the african green monkey as an alternate primate host for studying machupo virus infection.african green monkeys (cercopithecus aethiops) are highly susceptible to bolivian hemorrhagic fever (bhf). six monkeys were inoculated with 1,000 plague-forming units of machupo virus, the etiologic agent of bhf. they were observed and monitored for clinical signs, body temperature, viremia, hematologic changes, and virus neutralizing antibody. onset of fever, anorexia, and depression was noted on days 3 to 6 postinoculation. these and other signs increased in severity and all monkeys died: 5 of ...1977402863
directions for future research on the pathogenesis of arenaviral infections.the pathogenesis of arenavirus infection is considered separately for the haemorrhagic fever (hf) syndrome and for lymphocytic choriomeningitis (lcm) virus infection of rodents. experimental models of hf have received only limited study, mainly because of the virulence of the causal agents. two useful models (junin virus in guinea-pigs and machupo virus in rhesus monkeys) are now available and an attempt is made to delineate crucial questions for future studies, including the physiology of shock ...19751085229
sequence of the nucleocapsid protein gene of machupo virus: close relationship with another south american pathogenic arenavirus, junín.the sequence of the nucleocapsid (n) protein of machupo virus (causative agent of bolivian haemorrhagic fever) has been determined, and used to infer a phylogenetic relationship to other arenaviruses. the relationship of the virus to junín and tacaribe viruses, together with previous demonstrations of antigenic similarity and cross-protection by heterologous viruses, suggest that vaccines developed against argentine haemorrhagic fever might also be effective against the bolivian disease.19921318712
[the isolation of concentrated preparations of the machupo virus]. 19921329358
[monoclonal antibodies to the machupo virus: their isolation and preliminary characteristics].six monoclonal antibody-producing hybridoma cell lines were generated by fusion of ns-1 myeloma cells with balb/c immune splenocytes. monoclonal antibodies (mca) specific to machupo virus np protein were used to study cross-reactivity between pathogenic and nonpathogenic arenaviruses. it was shown that 3140 mca cross-reacted in ifa with lassa, tacaribe, and tamiami arenaviruses whereas 3101 mca reacted with machupo virus alone. it was assumed that these 3101 mca could be used for differentiation ...19911723822
properties and characterization of monoclonal antibodies to tacaribe virus.monoclonal antibodies prepared against tacaribe and junin viruses have been used to define further the serological relationships between arenaviruses of the tacaribe complex. a close relationship was found between these two viruses and the heterologous amapari and machupo viruses, with pichinde virus and parana virus being more distantly related. among the antibodies specific for tacaribe virus, five were found to react with viral antigens at the surface of infected cells and to neutralize virus ...19852410550
[interferon-inducing activity and sensitivity to urea of machupo virus variants]. 19892474907
epidemiology of hemorrhagic fever viruses.twelve distinct viruses associated with hemorrhagic fever in humans are classified among four families: arenaviridae, which includes lassa, junin, and machupo viruses; bunyaviridae, which includes rift valley fever, crimean-congo hemorrhagic fever, and hantaan viruses; filoviridae, which includes marburg and ebola viruses; and flaviviridae, which includes yellow fever, dengue, kyasanur forest disease, and omsk viruses. most hemorrhagic fever viruses are zoonoses, with the possible exception of t ...19892546247
[experimental infection caused by machupo virus in intact and immunosuppressed albino mice].features of the course of experimental infection in white mice caused by machupo virus in relation to their age, route of virus inoculation, and under conditions of normal and suppressed immune response created by antithymocyte globulin (atg) were studied. the effect of different atg doses and intervals of its administration on the experimental infection were demonstrated.19892561236
[pathogenic machupo and lassa arenaviruses: the biochemical properties of virion rna and proteins].lassa virus purified in the isodensity sucrose concentration gradient had the following buoyant densities: 1.17 g/cm3 (sucrose), 1.19 g/cm3 (cesium chloride), 1.16 g/cm3 (urografin). similar parameters were obtained for machupo virus. virion rnas of these viruses contained 5 sedimentation classes of molecules: 30-31s, 28s, 22-24s, 18s, and 4-6s. experiments on hybridization of individual sedimentation classes of rna with an excess of poly(a)-containing rna from the infected cells as well as inhi ...19872825435
sedimentation analysis of the rnas isolated from interfering particles of lassa and machupo viruses.vero cells chronically infected with lassa virus as well as bhk-21 cells chronically infected with machupo virus produced particles interfering with the replication of homologous, but not heterogeneous viruses. rnas of standard virus particles contained 4 sedimentation classes of molecules: 28-31 s, 22-24s, 18 s and 4-6 s. the 28-31 s molecules were not present among the rnas of interfering particles of lassa and machupo viruses.19852869655
machupo virus polypeptides: identification by immunoprecipitation.the most abundant protein in purified machupo virions (corvallo strain) labelled with 14c-protein hydrolysate is a 64 k polypeptide which is associated with virion rnas. another structural polypeptide, 37 k, solubilized by nonionic detergent seems to be a major surface glycoprotein. in addition to this, a 78 k polypeptide and a minor 50 k polypeptide have been detected. in machupo virus infected cells three virus-specific polypeptides similar in size to those described for structural polypeptide ...19852994603
[characteristics of the subvirion components formed after the treatment of machupo virus with a nonionic detergent].machupo virus labeled with radioactive precursors of rna or protein synthesis was purified by isodensity ultracentrifugation in sucrose concentration gradient. the purified virus was disrupted with np-40 nonionic detergent in the presence of 1 m kcl, and subvirion fractions were separated by ultracentrifugation in urografin density gradient. this treatment resulted in formation of two subvirion components with a buoyant density 1.25-1.26 and 1.10-1.12 g/cm3 in urografin concentration gradient. t ...19852998095
indirect immunofluorescence, serum neutralization, and viremia responses of rhesus monkeys (macaca mulatta) to machupo virus.although indirect immunofluorescent antibody tests (ifat) have been developed for several arenaviruses, none has been applied to the rhesus monkey model for bolivian hemorrhagic fever (caused by the arenavirus machupo). we infected eight rhesus monkeys with machupo virus and bled them weekly for determination of viremia and for serum antibody detection by ifat and serum neutralization (sn) testing. viremia peaked day 14 post-inoculation (pi), when two of eight animals had low ifat titers. at day ...19863014062
[sedimentation characteristics of virion rna of machupo virus reproducing in the presence of actinomycin d].actinomycin d treatment (0.005-05 g/ml) of vero and bhk-21 cells infected with machupo virus suppressed the synthesis of ribosomal rnas but did not affect the production of infectious machupo virus. virion rnas contained 3 high molecular weight rna species: 28-31 s, 22-24 s and 18 s. in the presence of actinomycin d [3h]-uridine incorporated only in 30-31 s and 22-24 s rna species. the data are supported by previous results which show that machupo virus genome contains two rna species: "large" ( ...19853025713
in vitro translation of mrna species from cells infected with machupo virus.rna from machupo virus infected cells was centrifuged in a linear sucrose gradient and rnas from gradient fractions were tested separately for template activity in a cell-free protein synthesizing system from rabbit reticulocytes. fraction 15-16 s programmed the synthesis of protein that migrated in sds-polyacrylamide gel like the nucleocapsid protein of a purified virus. the synthesis of virus glycoproteins was not detected in the system.19873028336
some characteristics of machupo virus, causative agent of bolivian hemorrhagic fever. 19674378149
measurement of antibodies to machupo virus by the indirect fluorescent technique. 19734570041
chronic infection of rodents by machupo virus.machupo virus, the etiologic agent of human hemorrhagic fever in bolivia, induced chronic asymptomatic infection in laboratory hamsters and colonized individuals of the peridomestic, wild, south american rodent, calomys callosus. viruria was detected for more than 500 and 150 days, respectively, in the two species. chronic viremia was shown only for calomys. virus-neutralizing substances were present in parenterally infected adult animals, but not in animals born to, and in contact with, an infe ...19654956127
use of oral swabs for detection of machupo-virus infection in rodents. 19685692124
multiplication of machupo virus, the etiological agent of bolivian hemorrhagic fever, in cell cultures. 19695765269
immune tolerance in calomys callosus infected with machupo virus. 19695787102
properties of machupo virus. 19655829140
epidemiology of machupo virus infection. i. pattern of human infection, san joaquín, bolivia, 1962-1964. 19655829142
epidemiology of machupo virus infection. 3. significance of virological observations in man and animals. 19655829143
epidemiology of machupo virus infection. ii. ecological and control studies of hemorrhagic fever. 19655890293
isolation of machupo virus from wild rodent calomys callosus. 19665901620
[chronic infection of bhk-21 cells by the machupo virus. the development of the system and properties of the virus produced by cells of this line].a new model of chronic infection of bhk-21 cells with machupo virus has been obtained. the chronically infected culture of bhk-21-m cells differed morphologically from the control culture by the presence of giant mono- and multinuclear forms with granular cytoplasm and by an increase in the number of small rounded cells. in the system of bhk-21-m cells, the persisting virus was produced permanently but the per cent of infected cells determined by indirect immunofluorescence and the infectious ce ...19846087564
[effect of actinomycin d on the reproduction of the machupo virus].the effect of inhibitors of mrna synthesis (actinomycin d and alpha-amanitin) and dna replication (mitomycin c and ethidium bromide) on machupo virus reproduction was studied. actinomycin d (1.0-4.0 micrograms/ml) and alpha-amanitin (10.0 micrograms/ml) added immediately after adsorption reduced the infectious virus titre by 2 lg or more. actinomycin d inhibited virus reproduction not only at the early but also at the later stages of infection. mitomycin c and ethidium bromide did not inhibit ma ...19846097044
monoclonal antibodies to lymphocytic choriomeningitis virus react with pathogenic arenaviruses.certain arenaviruses have become widely recognized as important human pathogens, the most notable among these being lassa virus, the causative agent of lassa fever. two other members of the group, junin and machupo virus, are the aetiological agents of argentine and bolivian haemorrhagic fevers, respectively. all these agents share both morphological features and to varying degrees serological cross-reactivity with other non-pathogenic arenaviruses. despite the evident clinical importance of the ...19806160402
[sedimentation analysis of the virion rna of machupo virus].pichinde and machupo viruses labeled with 3h-uridine were concentrated and purified by different methods. the buoyant density of the viruses was for pichinde 1.14-1.15 g/cm3 (urographimeter), 1.19 g/cm3 (sucrose), 1.25 g/cm3 (cesium chloride), for machupo virus 1.25 g/cm3 (cesium chloride). virion rnas of pichinde and machupo viruses were divided in sucrose concentration gradient into 4 sedimentation classes: 7-10 s, 18 s, 20-22 s, and 28-30 s. virion 28 s and 18 s rnas cosedimented with ribosom ...19836314674
ribonucleic acids of machupo and lassa viruses.sucrose gradient velocity centrifugation, polyacrylamide gel electrophoresis and rna-rna hybridization were used to characterize lassa and machupo virion rnas as well as virus-specific rnas from cells infected with pichinde and machupo viruses. five rna species: 30-31s, 28s, 22-24s, 18s and 4-6s have been detected in lassa, machupo, and pichinde virion rnas. among them 28s, 18s and 4-6s rnas cosediment and comigrate with respectively cell rnas. rnase resistance analyses suggest the presence of e ...19846320777
[accumulation of certain arenaviruses in transplantable vero and bhk-21 cells].production of lassa and machupo viruses in vero and bhk-21 cells was studied in relation to various conditions of the infected cell cultivation and as a function of different multiplicities of infection. the highest titers (expressed in pfu/ml) were obtained when the cells were grown in roller bottles with daily changes of the medium. the maximum titer in lassa virus-infected cells was over 10(6), in machupo virus-infected cells over 10(7). the effect of the autointerfering factor on the growth ...19817269524
bolivian hemorrhagic fever--el beni department, bolivia, 1994.in july 1994, an outbreak of bolivian hemorrhagic fever (bhf), which is caused by machupo virus, began in northeastern bolivia. this report describes the investigation and features of this outbreak, the search for additional cases of bhf in el beni, bolivia, and results of rodent investigations.19947990799
latin american hemorrhagic fever.several viral and bacterial agents are responsible for hemorrhagic fever in latin america, but there are three agents that are only present in this region: (1) the junin virus, (2) the machupo virus, and (3) the guanaritovirus, members of the tacaribe complex of the family arenaviridae and responsible for the argentinian, bolivian, and venezuelan hemorrhagic fever. the clinical manifestations of hemorrhagic fever are similar for the three viruses, mainly myalgia, arthralgia, headache, relative b ...19948021448
[the immunity indices in the infection of mice of different strains with the machupo virus].the pathomorphological patterns and the activity of serum interferon, interleukin-1, tumor necrosis factor, natural killers, and proliferative activity of lymphocytes were studied in balb/c and c57b1/6 mice intracerebrally infected with machupo virus. the balb/c mice showed 100% lethality at 8-9 days after inoculation while c57b1/6 mice were found nonsusceptible to machupo virus inoculation by this route. the pathomorphological findings at the peak of clinical manifestations in balb/c mice revea ...19938236941
[the immunity indices of balb/c mice immunized with an inactivated antigen of the machupo virus].the paper presents the data characterizing parameters of specific and nonspecific immunity in balb/c mice immunized with gamma-ray-inactivated machupo virus antigen or its formalinized antigen. the gamma-ray inactivated preparation was shown to be more immunogenic for balb/c mice. a certain relationship between the time course of activity of nonspecific immunity factors in the immunized animals and the protective activity of the preparation under study was also noted. the decisive role of the t- ...19938284923
[experimental study of the possibility of emergency prophylaxis of bolivian hemorrhagic fever].describes changes in nonspecific immunity parameters (interferon, interleukin-1, tumor necrosis factor, and natural killers) in the course of experimental bolivian fever (machupo virus). changes of these parameters were followed up after urgent prophylactic injections of ridostin and specific gamma-globulin to infected animals. the possibility of treatment of experimental machupo fever by intranasal administration of interferon inductor ridostin has been demonstrated.19958659175
treatment of bolivian hemorrhagic fever with intravenous ribavirin.bolivian hemorrhagic fever (bhf) is a potentially severe febrile illness caused by machupo virus (family arenaviridae). initial symptoms include headache, fever, arthralgia, and myalgia. in the later stages of this illness, patients may develop hemorrhagic manifestations including subconjunctival hemorrhage, epistaxis, hematemesis, melena, and hematuria, as well as neurological signs including tremor, seizures, and coma. during the bhf epidemics of the 1960s, convalescent-phase immune plasma fro ...19979145749
[immunologic indicators in vaccinated mice with machupo virus infection].the parameters of nonspecific immunity (interferon, interleukin-1, tumor necrosis factor, and natural killers) changed in immune balb/c mice after challenge with machupo virus in doses of 1000 and 5000 pfu. after challenge with 1000 pfu the activity of the above parameters increased during the first three days and no cases of animal death occurred. after challenge with 5000 pfu the maximal values of interferon, interleukin-1, tumor necrosis factor, and natural killers were observed on days 5-7, ...19979297347
imported viral haemorrhagic fever with a potential for person-to-person transmission: review and recommendations for initial management of a suspected case in belgium.viral haemorrhagic fevers are caused by a wide range of viruses. there are 4 types of viruses well known to spread from person to person and able to cause nosocomial outbreaks with a high case fatality rate: an arenavirus (lassa fever and more exceptionally the junin and machupo virus), a bunyavirus (crimean-congo haemorrhagic fever) and the filoviridae (ebola and marburg viruses). so far there have been only a limited number of imported cases of viral haemorrhagic fever in industrialized countr ...200212534129
natural nidality in bolivian hemorrhagic fever and the systematics of the reservoir species.zoonoses within wild reservoir host populations often occur focally obeying pavlovskii's rules of "natural nidality". what appears to be a clear example is bolivian hemorrhagic fever (bhf), a disease endemic to northeastern bolivia. the etiological agent is machupo virus (macv, arenaviridae). the vertebrate reservoir, identified 30 years ago, was calomys callosus a wild rodent common to open biomes in the lowlands of southeastern south america. the lack of concordance between the occurrence of m ...200212798015
receptor use by pathogenic arenaviruses.the arenavirus family contains several important human pathogens including lassa fever virus (lasv), lymphocytic choriomeningitis virus (lcmv) and the new world clade b viruses junin (junv) and machupo (macv). previously, alpha-dystroglycan (alpha-dg) was identified as a receptor recognized by lasv and certain strains of lcmv. however, other studies have suggested that alpha-dg is probably not used by the clade b viruses, and the receptor(s) for these pathogens is currently unknown. using pseudo ...200616797051
[hemorrhagic (marburg, ebola, lassa, and bolivian) fevers: epidemiology, clinical pictures, and treatment].the evaluation of the biological and epidemiological properties of ebola, marburg, lassa, and machupo viruses suggests that they are of social importance for health care authorities. the studies have created prerequisites to the development of reliable biosafety means against these pathogens. particular emphasis is laid on the methods for infection diagnosis and on the studies to design specific protective agents--immunoglobulins and inactivated vaccines.200617087059
transferrin receptor 1 is a cellular receptor for new world haemorrhagic fever arenaviruses.at least five arenaviruses cause viral haemorrhagic fevers in humans. lassa virus, an old world arenavirus, uses the cellular receptor alpha-dystroglycan to infect cells. machupo, guanarito, junin and sabia viruses are new world haemorrhagic fever viruses that do not use alpha-dystroglycan. here we show a specific, high-affinity association between transferrin receptor 1 (tfr1) and the entry glycoprotein (gp) of machupo virus. expression of human tfr1, but not human transferrin receptor 2, in ha ...200717287727
differences in tropism and ph dependence for glycoproteins from the clade b1 arenaviruses: implications for receptor usage and pathogenicity.the clade b lineage of the new world arenaviruses contains four viruses capable of causing severe hemorrhagic fevers in humans. within this group, the b1 sub-lineage contains the pathogenic viruses junin (junv) and machupo (macv), as well as the non-pathogenic tacaribe virus (tcrv). in order to elucidate differences that may determine pathogenicity, we studied the entry pathways directed by the glycoproteins (gps) from these related b1 viruses, using pseudotyped retroviral vectors and gp1 immuno ...200717397892
cell entry by human pathogenic arenaviruses.the arenaviruses lassa virus (lasv) in africa and machupo (macv), guanarito (gtov) and junin viruses (junv) in south america cause severe haemorrhagic fevers in humans with fatality rates of 15-35%. the present review focuses on the first steps of infection with human pathogenic arenaviruses, the interaction with their cellular receptor molecules and subsequent entry into the host cell. while similarities exist in genomic organization, structure and clinical disease caused by pathogenic old worl ...200818182084
receptor determinants of zoonotic transmission of new world hemorrhagic fever arenaviruses.transferrin receptor 1 (tfr1) is a cellular receptor for the new world hemorrhagic fever arenaviruses machupo (macv), junín (junv), and guanarito (gtov). each of these viruses is specifically adapted to a distinct rodent host species, but all cause human disease. here we compare the ability of these viruses to use various mammalian transferrin receptor 1 (tfr1) orthologs, including those of the south american rodents that serve as reservoirs for macv, junv, and gtov (calomys callosus, calomys mu ...200818268337
genetic diversity among bolivian arenaviruses.machupo virus and chapare virus are members of the tacaribe serocomplex (virus family arenaviridae) and etiological agents of hemorrhagic fever in humans in bolivia. the nucleotide sequences of the complete z genes, a large fragment of the rna-dependent rna polymerase genes, the complete glycoprotein precursor genes, and the complete nucleocapsid protein genes of 8 strains of machupo virus were determined to increase our knowledge of the genetic diversity among the bolivian arenaviruses. the res ...200919041349
models for an arenavirus infection in a rodent population: consequences of horizontal, vertical and sexual transmission.arenaviruses are associated with rodent-transmitted diseases in humans. five arenaviruses are known to cause human illness: lassa virus, junin virus, machupo virus, guanarito virus and sabia virus. in this investigation, we model the spread of machupo virus in its rodent host calomys callosus. machupo virus infection in humans is known as bolivian hemorrhagic fever (bhf) which has a mortality rate of approximately 5-30% [31]. machupo virus is transmitted among rodents through horizontal (direct ...200819278272
non-infectious plasmid engineered to simulate multiple viral threat agents.the aim of this study was to design and construct a non-virulent simulant to replace several pathogenic viruses in the development of detection and identification methods in biodefense. a non-infectious simulant was designed and engineered to include the nucleic acid signature of veev (venezuelan equine encephalitis virus), influenza virus, rift valley fever virus, machupo virus, lassa virus, yellow fever virus, ebola virus, eastern equine encephalitis virus, junin virus, marburg virus, dengue v ...200919442841
unusual molecular architecture of the machupo virus attachment glycoprotein.new world arenaviruses, which cause severe hemorrhagic fever, rely upon their envelope glycoproteins for attachment and fusion into their host cell. here we present the crystal structure of the machupo virus gp1 attachment glycoprotein, which is responsible for high-affinity binding at the cell surface to the transferrin receptor. this first structure of an arenavirus glycoprotein shows that gp1 consists of a novel alpha/beta fold. this provides a blueprint of the new world arenavirus attachment ...200919494008
characterization of monoclonal antibodies to junin virus nucleocapsid protein and application to the diagnosis of hemorrhagic fever caused by south american arenaviruses.junin virus (junv), machupo virus, guanarito virus, sabia virus, and chapare virus are members of new world arenavirus clade b and are the etiological agents of viral hemorrhagic fevers that occur in south america. in this study, we produced three monoclonal antibodies (mabs) to the recombinant nucleocapsid protein of junv, designated c6-9, c11-12, and e4-2. the specificity of these mabs was examined by enzyme-linked immunosorbent assay (elisa), indirect immunofluorescence assay, and an epitope- ...200919553554
[use of guinea pigs to evaluate the efficacy of a heterological immunoglobulin against bolivian hemorrhagic fever].the use of guinea pigs as a laboratory model was proven to be appropriate in investigating the protective properties of a heterological immunoglobulin against bolivian hemorrhagic fever at the preclinical stage of the study. a highly pathogenic machupo virus strain that caused guinea pigs' death with respect with an agent's dose was cultivated. injection of 1.0 ml of the immunoglobulin provided a 100% protective effect for the guinea pigs infected with the highly pathogenic machupo virus strain ...200919708556
investigation of clade b new world arenavirus tropism by using chimeric gp1 proteins.clade b of the new world arenaviruses contains both pathogenic and nonpathogenic members, whose surface glycoproteins (gps) are characterized by different abilities to use the human transferrin receptor type 1 (htfr1) protein as a receptor. using closely related pairs of pathogenic and nonpathogenic viruses, we investigated the determinants of the gp1 subunit that confer these different characteristics. we identified a central region (residues 85 to 221) in the guanarito virus gp1 that was suffi ...201019889757
the role of the vascular endothelium in arenavirus haemorrhagic fevers.viral haemorrhagic fevers (vhf) caused by arenaviruses are among the most devastating emerging human diseases. the most important pathogen among the arenaviruses is lassa virus (lasv), the causative agent of lassa fever that is endemic to west africa. on the south american continent, the new world arenavirus junin virus (junv), machupo (macv), guanarito (gtov), and sabia virus (sabv) have emerged as causative agents of severe vhfs. clinical and experimental studies on arenavirus vhf have reveale ...200919967131
z proteins of new world arenaviruses bind rig-i and interfere with type i interferon induction.the retinoic acid-inducible gene i product (rig-i) is a cellular sensor of rna virus infection that regulates the cellular beta interferon (ifn-beta) response. the nucleoproteins (np) of arenaviruses are reported to antagonize the ifn response by inhibiting interferon regulatory factor 3 (irf-3). here, we demonstrate that the z proteins of four new world (nw) arenaviruses, guanarito virus (gtov), junin virus (junv), machupo virus (mavc), and sabia virus (sabv), bind to rig-i, resulting in downre ...201020007272
[chemotherapy for bolivian hemorrhagic fever in experimentally infected guinea pigs].the efficacy of the antiviral agents nucleoside analogues manufactured in russia and foreign countries against bolivian hemorrhagic fever in the treatment and rapid prevention regimens was studied in guinea pigs. in rapid prevention and treatment of guinea pigs, the intraperitoneal injection of 1/10 of the equivalent dose of vero-ribavirin for this animal species was ascertained to protect 70% of the animals infected with machupo virus strain carvallo in doses 8 and 10 ld50.200920030281
structural basis for receptor recognition by new world hemorrhagic fever arenaviruses.new world hemorrhagic fever arenaviruses are rodent-borne agents that cause severe human disease. the gp1 subunit of the surface glycoprotein mediates cell attachment through transferrin receptor 1 (tfr1). we report the structure of machupo virus (macv) gp1 bound with human tfr1. atomic details of the gp1-tfr1 interface clarify the importance of tfr1 residues implicated in new world arenavirus host specificity. analysis of sequence variation among new world arenavirus gp1s and their host-species ...201020208545
a multivalent vaccination strategy for the prevention of old world arenavirus infection in humans.arenaviruses cause severe human disease ranging from aseptic meningitis following lymphocytic choriomeningitis virus (lcmv) infection to hemorrhagic fever syndromes following infection with guanarito virus (gtov), junin virus (junv), lassa virus (lasv), machupo virus (macv), sabia virus (sabv), or whitewater arroyo virus (wwav). cellular immunity, chiefly the cd8(+) t-cell response, plays a critical role in providing protective immunity following infection with the old world arenaviruses lasv an ...201020668086
infectious lassa virus, but not filoviruses, is restricted by bst-2/tetherin.bone marrow stromal antigen 2 (bst-2/tetherin) is a cellular membrane protein that inhibits the release of hiv-1. we show for the first time, using infectious viruses, that bst-2 also inhibits egress of arenaviruses but has no effect on filovirus replication and spread. specifically, infectious lassa virus (lasv) release significantly decreased or increased in human cells in which bst-2 was either stably expressed or knocked down, respectively. in contrast, replication and spread of infectious z ...201020686043
assembly of a functional machupo virus polymerase complex.segmented negative-sense viruses of the family arenaviridae encode a large polymerase (l) protein that contains all of the enzymatic activities required for rna synthesis. these activities include an rna-dependent rna polymerase (rdrp) and an rna endonuclease that cleaves capped primers from cellular mrnas to prime transcription. using purified catalytically active machupo virus l, we provide a view of the overall architecture of this multifunctional polymerase and reconstitute complex formation ...201020978208
t-705 (favipiravir) inhibition of arenavirus replication in cell culture.a number of new world arenaviruses (junín [junv], machupo [macv], and guanarito [gtov] viruses) can cause human disease ranging from mild febrile illness to a severe and often fatal hemorrhagic fever syndrome. these highly pathogenic viruses and the old world lassa fever virus pose a significant threat to public health and national security. the only licensed antiviral agent with activity against these viruses, ribavirin, has had mixed success in treating severe arenaviral disease and is associa ...201021115797
medical microbiologythe hallmark of arenaviruses is their tendency to cause persistent silent infections in their natural hosts (rodents) and severe, often lethal, disseminated disease in humans. arenaviruses are pleomorphic enveloped particles that contain two rna segments of virus origin and ribosome-like components. suitable conditions for transmission of virus to humans occur in areas where humans come in contact with rodent urine that contains virus. persistent viremia and viruria in rodents result from a slow ...199621413313
a stat-1 knockout mouse model for machupo virus pathogenesis.machupo virus (macv), a member of the arenaviridae, causes bolivian hemorrhagic fever, with ~20% lethality in humans. the pathogenesis of macv infection is poorly understood, and there are no clinically proven treatments for disease. this is due, in part, to a paucity of small animal models for macv infection in which to discover and explore candidate therapeutics.201121672221
machupo virus glycoprotein determinants for human transferrin receptor 1 binding and cell entry.machupo virus (macv) is a highly pathogenic new world arenavirus that causes hemorrhagic fever in humans. macv, as well as other pathogenic new world arenaviruses, enter cells after their gp1 attachment glycoprotein binds to their cellular receptor, transferrin receptor 1 (tfr1). tfr1 residues essential for this interaction have been described, and a co-crystal of macv gp1 bound to tfr1 suggests gp1 residues important for this association. we created macv gp1 variants and tested their effect on ...201121750710
viral diversity of jun+¡n virus field strains.the argentine hemorrhagic fever, an endemic disease present in a much of argentina, is caused by the jun+¡n virus (junv). currently, there are sequences available from several strains of this virus, like those belonging to the vaccine lineage (xj13, xj#44 and candid#1), as well as mc2 (rodent isolate) and iv4454 (human isolate). in this article, we report sequence information on two fragments of genomic segment s of viral isolates from the endemic area. a nested-rt-pcr was used to amplify discre ...201121689697
vaccine platforms to control arenaviral hemorrhagic fevers.arenaviruses are rodent-borne emerging human pathogens. diseases caused by these viruses, e.g., lassa fever (lf) in west africa and south american hemorrhagic fevers (hfs), are serious public health problems in endemic areas. we have employed replication-competent and replication-deficient strategies to design vaccine candidates potentially targeting different groups "at risk". our leader lf vaccine candidate, the live reassortant vaccine ml29, is safe and efficacious in all tested animal models ...201223420494
glycoprotein-specific antibodies produced by dna vaccination protect guinea pigs from lethal argentine and venezuelan hemorrhagic fever.several members of the arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. the use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in south america. despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. in the present study, we produced arenavirus neutralizing antibodies by dna vaccination of rabbits with plasmids encoding the ...201626792737
machupo virus expressing gpc of the candid#1 vaccine strain of junin virus is highly attenuated and immunogenic.machupo virus (macv) is the causative agent of bolivian hemorrhagic fever. our previous study demonstrated that a macv strain with a single amino acid substitution (f438i) in the transmembrane domain of glycoprotein is attenuated but genetically unstable in mice. macv is closely related to junin virus (junv), the causative agent of argentine hemorrhagic fever. others and our group have identified the glycoprotein to be the major viral factor determining junv attenuation. in this study, we tested ...201526581982
mission critical: mobilization of essential animal models for ebola, nipah, and machupo virus infections.the reports for ebola virus zaire (ebov), nipah virus, and machupo virus (macv) pathogenesis, in this issue of veterinary pathology, are timely considering recent events, both nationally and internationally. ebov, nipah virus, and macv cause highly lethal infections for which no food and drug administration (fda) licensed vaccines or therapies exist. not only are there concerns that these agents could be used by those with malicious intent, but shifts in ecological distribution of viral reservoi ...201525352204
diseases of the central nervous system caused by lymphocytic choriomeningitis virus and other arenaviruses. 201425015511
inhibition of arenavirus infection by a glycoprotein-derived peptide with a novel mechanism.the family arenaviridae includes a number of viruses of public health importance, such as the category a hemorrhagic fever viruses lassa virus, junin virus, machupo virus, guanarito virus, and sabia virus. current chemotherapy for arenavirus infection is limited to the nucleoside analogue ribavirin, which is characterized by considerable toxicity and treatment failure. using pichinde virus as a model arenavirus, we attempted to design glycoprotein-derived fusion inhibitors similar to the fda-app ...201424850726
drug discovery technologies and strategies for machupo virus and other new world arenaviruses.seven arenaviruses cause viral hemorrhagic fever in humans: the old world arenaviruses lassa and lujo, and the new world clade b arenaviruses machupo (macv), junín (junv), guanarito (gtov), sabiá (sabv), and chapare (chpv). all of these viruses are risk group 4 biosafety pathogens. macv causes human disease outbreak with high case-fatality rates. to date, at least 1,200 cases with ≈200 fatalities have been recorded.201222607481
architecture and regulation of negative-strand viral enzymatic machinery.negative-strand (ns) rna viruses initiate infection with a unique polymerase complex that mediates both mrna transcription and subsequent genomic rna replication. for nearly all ns rna viruses, distinct enzymatic domains catalyzing rna polymerization and multiple steps of 5' mrna cap formation are contained within a single large polymerase protein (l). while ns rna viruses include a variety of emerging human and agricultural pathogens, the enzymatic machinery driving viral replication and gene e ...201222767259
differences in glycoprotein complex receptor binding site accessibility prompt poor cross-reactivity of neutralizing antibodies between closely related arenaviruses.the glycoprotein complex (gpc) of arenaviruses, composed of stable signal peptide, gp1, and gp2, is the only antigen correlated with antibody-mediated neutralization. however, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. two closely related clade b viruses, machupo virus (macv) and junín virus (junv), have nearly identical overall gpc architecture and share a host receptor, transferrin receptor 1 (tfr1). give ...201728100617
the ectodomain of glycoprotein from the candid#1 vaccine strain of junin virus rendered machupo virus partially attenuated in mice lacking ifn-αβ/γ receptor.machupo virus (macv), a new world arenavirus, is the etiological agent of bolivian hemorrhagic fever (bhf). junin virus (junv), a close relative, causes argentine hemorrhagic fever (ahf). previously, we reported that a recombinant, chimeric macv (rmacv/cd#1-gpc) expressing glycoprotein from the candid#1 (cd#1) vaccine strain of junv is completely attenuated in a murine model and protects animals from lethal challenge with macv. a rmacv with a single f438i substitution in the transmembrane domain ...201627580122
highly pathogenic new world and old world human arenaviruses induce distinct interferon responses in human cells.the arenavirus family includes several important pathogens that cause severe and sometimes fatal diseases in humans. the highly pathogenic old world (ow) arenavirus lassa fever virus (lasv) is the causative agent of lassa fever (lf) disease in humans. lasv infections in severe cases are generally immunosuppressive without stimulating interferon (ifn) induction, a proinflammatory response, or t cell activation. however, the host innate immune responses to highly pathogenic new world (nw) arenavir ...201525926656
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, ...201222258244
computational and functional analysis of the virus-receptor interface reveals host range trade-offs in new world arenaviruses.animal viruses frequently cause zoonotic disease in humans. as these viruses are highly diverse, evaluating the threat that they pose remains a major challenge, and efficient approaches are needed to rapidly predict virus-host compatibility. here, we develop a combined computational and experimental approach to assess the compatibility of new world arenaviruses, endemic in rodents, with the host tfr1 entry receptors of different potential new host species. using signatures of positive selection, ...201526355089
pathogenesis of bolivian hemorrhagic fever in guinea pigs.machupo virus, the cause of bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no food and drug administration-approved vaccines or therapeutics. this study evaluated the guinea pig as a model using the machupo virus-chicava strain administered via aerosol challenge. guinea pigs (cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. the incubation p ...201626139838
a substitution in the transmembrane region of the glycoprotein leads to an unstable attenuation of machupo virus.machupo virus (macv) is the etiologic agent of bolivian hemorrhagic fever (bhf). utilizing a reverse-genetics system recently developed, we report the rescue of a rationally modified recombinant macv containing a single mutation in the transmembrane region of the glycoprotein. following challenge of susceptible mice, we identified a significant reduction in virulence in the novel virus. we also identified an instability leading to reversion of the single mutation to a wild-type genotype.201425031335
pathology of experimental machupo virus infection, chicava strain, in cynomolgus macaques (macaca fascicularis) by intramuscular and aerosol exposure.machupo virus, the causative agent of bolivian hemorrhagic fever (bhf), is a highly lethal viral hemorrhagic fever of which little is known and for which no food and drug administration-approved vaccines or therapeutics are available. this study evaluated the cynomolgus macaque as an animal model using the machupo virus, chicava strain, via intramuscular and aerosol challenge. the incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial ...201524990481
epidemiology and pathogenesis of bolivian hemorrhagic fever.the etiologic agent of bolivian hemorrhagic fever (bhf), machupo virus (macv) is reported to have a mortality rate of 25-35%. first identified in 1959, bhf was the cause of a localized outbreak in san joaquin until rodent population controls were implemented in 1964. the rodent calomys collosus was identified as the primary vector and reservoir for the virus. multiple animal models were considered during the 1970s with the most human-like disease identified in rhesus macaques but minimal charact ...201424636947
analyzing machupo virus-receptor binding by molecular dynamics simulations.in many biological applications, we would like to be able to computationally predict mutational effects on affinity in protein-protein interactions. however, many commonly used methods to predict these effects perform poorly in important test cases. in particular, the effects of multiple mutations, non alanine substitutions, and flexible loops are difficult to predict with available tools and protocols. we present here an existing method applied in a novel way to a new test case; we interrogate ...201424624315
rescue of a recombinant machupo virus from cloned cdnas and in vivo characterization in interferon (αβ/γ) receptor double knockout mice.machupo virus (macv) is the etiological agent of bolivian hemorrhagic fever (bhf), a reemerging and neglected tropical disease associated with high mortality. the prototypical strain of macv, carvallo, was isolated from a human patient in 1963, but minimal in vitro and in vivo characterization has been reported. to this end, we utilized reverse genetics to rescue a pathogenic macv from cloned cdnas. the recombinant macv (rmacv) had in vitro growth properties similar to those of the parental macv ...201424284323
virions at the gates: receptors and the host-virus arms race.all viruses need to bind to specific receptor molecules on the surface of target cells to initiate infection. virus-receptor binding is highly specific, and this specificity determines both the species and the cell type that can be infected by a given virus. in some well-studied cases, the virus-binding region on the receptor has been found to be unrelated to the receptor's normal cellular function. resistance to virus infection can thus evolve by selection of mutations that alter amino acids in ...201323723739
in vitro and in vivo characterizations of pichinde viral nucleoprotein exoribonuclease functions.arenaviruses cause severe hemorrhagic fever diseases in humans, and there are limited preventative and therapeutic measures against these diseases. previous structural and functional analyses of arenavirus nucleoproteins (nps) revealed a conserved deddh exoribonuclease (rnase) domain that is important for type i interferon (ifn) suppression, but the biological roles of the np rnase in viral replication and host immune suppression have not been well characterized. infection of guinea pigs with pi ...201525878103
[a prototype of oligonucleotide microarray for detection of pathogens relating to arena- and filoviridae families].a prototype of oligonucleotide microarray for detection of lassa, junin, machupo, guanarito viruses (arenaviridae family), ebola and marburg viruses (filoviridae family) was presented. an original approach founded on virus proteins (nucleocapsid protein for junin, guanarito, machupo viruses and rna-dependent rna-polymerase for lassa, ebola and marburg viruses) amino acid sequences analysis with subsequent transform of revealed unique peptides into due sets of oligonucleotides was used to design ...201526050472
Displaying items 1 - 100 of 106