experimental biology and pathogenesis of junin virus infection in animals and man.a fatal disease resembling argentine haemorrhagic fever of man has been produced in guinea-pigs and mice by inoculation with junin virus. infected guinea-pigs show macroscopic and microscopic haemorrhagic lesions, marked bone marrow changes, decreased leukocytes and platelets in the peripheral blood, and impairment of immunological response. this response permits differentiation between pathogenic (xj) and attenuated (xj cl(3)) strains. guinea-pigs inoculated with the xj cl(3) strain develop an ...1975182401
argentine hemorrhagic fever: a primate model.experimental junin virus infection of a new world primate, callithrix jacchus, was evaluated. the virus produced anorexia, loss of weight, thrombocytopenia, leukopenia, and hemorrhagic and neurological symptoms and terminated in death. virus was recovered from urine, blood samples and all tissues taken at autopsy. these preliminary observations show that several aspects of the experimental disease in c. jacchus are quite similar to severe natural argentine hemorrhagic fever of man.1979227811
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
candid no. 1 argentine hemorrhagic fever vaccine protects against lethal junin virus challenge in rhesus macaques.the protective efficacy of candid no. 1, a live-attenuated vaccine against argentine hemorrhagic fever (ahf), was evaluated in non-human primates. twenty rhesus macaques immunized 3 months previously with graded doses of candid no. 1 (16-127, 000 pfu), as well as 4 placebo-inoculated controls, were challenged with 4.41 log10 pfu of virulent p3790 strain junin virus. all controls developed severe clinical disease; 3 of 4 died. in contrast, all vaccinated animals were fully protected; none develop ...19921338783
toward a vaccine against argentine hemorrhagic fever.a vaccine against argentine hemorrhagic fever, the "mal de los rastrojos" of the pampas, has been a dream of physicians and scientists involved with the disease since its recognition in the 1950s. several killed and live immunogens have been produced and tested in pursuit of this goal, none of which has proved suitable for widespread human use. recently, a new live-attenuated junin virus vaccine, candid #1, was developed through a cooperative international effort. testing conducted to date indic ...19911654168
protection of guinea pigs against experimental argentine hemorrhagic fever by purified human igg: importance of elimination of infected cells.antibody-containing plasma from patients recovered from argentine hemorrhagic fever (ahf) is of proven value in treatment of the acute disease, but the possibility of transmitting blood-borne organisms such as hiv and hepatitis virus detracts from this approach. purified human immune plasma fractions igg1,2,4, igg1,2,3,4 and f(ab')2 neutralized junin virus in vitro. igg1,2,3,4 and igg1,2,4 lysed (in the presence of complement) cells infected with junin virus, and protected infected guinea pigs f ...19901965845
a refined complement-enhanced neutralization test for detecting antibodies to junin virus.a refined, complement-enhanced, plaque-reduction neutralization test was developed for measuring neutralizing antibodies against junin (argentine hemorrhagic fever) virus. the assay measured neutralizing antibodies after natural as well as vaccine-induced junin virus infections. among vaccinated individuals, titers were 2-4-fold higher than those obtained with conventional assays, without loss of specificity. enhanced sensitivity was achieved by using a standardized complement source (vs human o ...19902170437
susceptible adult murine model for junin virus.the adult mouse model had been considered resistant to junin virus (jv) infection. however, we found that c3h/hej murine strain proved highly susceptible up to 5 months of age to intracerebral inoculation with the prototype xj jv strain, showing neurological signs and 80-90% mortality within 13 days. neutralizing antibodies (nt ab) were absent, but low immunofluorescent ab levels (1:5) were detected as from day +7. the virus could only be rescued by coculture of brain samples with vero cells. hi ...19882850346
pathogenesis of attenuated junin virus in the guinea pig model.the purpose of this work was to elucidate the pathogenesis of attenuated junin virus (jv) strains in the guinea pig model. three groups of guinea pigs were infected by the im route with 10(3) pfu of the xjc13 and xjo-attenuated strains or with the xj pathogenic strain of jv, respectively. viremia was studied at 3, 5, 7, 9, 12, and 14 days postinfection (pi) (a) in serum samples of all animals and in washed cells from xjc13-infected guinea pigs by conventional techniques and (b) in whole blood sa ...19852983013
treatment of junin virus-infected guinea pigs with immune serum: development of late neurological disease.guinea pigs infected with argentine hemorrhagic fever virus (junin) were treated with pooled, homologous convalescent sera. use of 15,000 or 5,000 therapeutic units of immune sera prevented all signs of illness when administered within 24 hr of infection. we could also prevent illness and death in infected guinea pigs as late as 6 days after infection if we used more antisera (30,000 therapeutic units/kg). in some treatment groups, surviving animals developed a late neurological syndrome with pr ...19863023540
protection of junín virus-infected marmosets by passive administration of immune serum: association with late neurologic signs.argentine hemorrhagic fever (junín virus) is a human viral disease for which immune therapy proves effective, though a late neurologic syndrome is occasionally associated with the treatment. we attempted to determine in the infected marmoset callithrix jacchus whether immune therapy leads to protection and/or cns damage. fifteen c jacchus were inoculated with 10(3) tissue culture infectious dose 50% (tcid50) of the xj strain of junín virus. on day 6 post infection (pi), 12 primates were treated ...19873025358
in vitro inactivation of complement by a serum factor present in junin-virus infected guinea-pigs.a serum factor(s) of guinea-pigs infected with junin virus, the etiological agent of argentine haemorrhagic fever, is endowed with a potent anticomplementary activity. it is resistant to heat (56 degrees, 30 min) and elutes from a sephadex g-200 column between albumin and haemoglobin. it is ineffective in the presence of edta or egta and does not sediment at 82,000 g. it has no direct effect on c4 unless functional cl is present. however, it induces cl activation that consumes c4 haemolytic acti ...19806247264
[new findings on junin virus infection in rodents inside and outside the endemic area of hemorrhagic fever in argentina].in conjunction with field trials for a vaccine against argentine hemorrhagic fever (ahf), small mammals were trapped during a 28-month period (1 november 1987 to 13 march 1990) in 3 epidemiologically defined areas of the central argentine pampas: northern and central buenos aires provinces were included in the ahf "historic" area, where the disease was common 15-20 years ago, but case rates are currently low; southern santa fe province is the current high-incidence area for ahf; the nonendemic a ...19917476104
a simple nucleic acid amplification assay for the rapid detection of junín virus in whole blood samples.argentine hemorrhagic fever (ahf) is an endemoepidemic disease with cardiovascular, renal and neurologic alterations acquired in the richest farming land in argentina. it is caused by junín virus, one of the few human pathogenic arenaviruses. the s rna of junín virus has been molecularly cloned and its nucleotide sequence determined in our laboratory. this information was used to develop a rapid nucleic acid-based diagnostic test commensurate with the low viraemia detected in ahf patients. junín ...19938383393
replication and physical parameters important for preparing purified junin virus.junin virus (jv) is an arenavirus and the causative agent of argentine hemorrhagic fever (ahf), an often fatal human disease. the attenuated strain xj-clone 3 (xjc13) of jv, after being tested in humans, has been considered a promising vaccine. we found that synthesis of jv xjc13 reaches a peak 2 days after infection and the kinetics of synthesis are little affected by the multiplicity of infection (moi) in a range from 0.125 to 1.00. virus synthesis is sensitive to actinomycin d, indicating tha ...19938388396
polysulfonates derived from metal thiolate complexes as inhibitors of hiv-1 and various other enveloped viruses in vitro.sodium 2-mercaptoethanesulfonate reacts with the metal ions pd(ii), pt(ii), ag(i), cd(ii) and zn(ii) to yield complexes containing multiple anionic sulfonate sites. on the basis of spectroscopic and other analytical data the complexes were assigned the tentative molecular formulas: pd6(sch2ch2so3na)12, ptn(sch2ch2so3na)2n+2, agn(sch2ch2so3na)n, na2zn4(sch2ch2so3na)10, and na2cd4(sch2ch2so3na)10. the complexes displayed a variety of differences in activity towards dna and rna viruses. the platinu ...200212448691
igg subclasses in human immune response to wild and attenuated (vaccine) junin virus infection.different proportions of igg subclasses have previously been reported to distinguish the immune response elicited by primary and recurrent viral infections, as well as viral vaccines. the goal of this study was to study the igg subclasses composition in the immune response of patients with argentine hemorrhagic fever, and vaccinees with candid #1 strain of junin virus. twenty-four individuals inoculated with candid #1 vaccine and 67 patients with argentine hemorrhagic fever were studied. blood s ...200312526057
virucidal activity of essential oils from aromatic plants of san luis, argentina.essential oils obtained from eight aromatic plants of san luis province, argentina, were screened for virucidal activity against herpes simplex virus type 1 (hsv-1), junin virus (junv) and dengue virus type 2 (den-2). the most potent inhibition was observed with the essential oil of lippia junelliana and lippia turbinata against junv with virucidal concentration 50% (vc(50)) values in the range 14-20 ppm, whereas aloysia gratissima, heterotheca latifolia and tessaria absinthioides inhibited junv ...200314595590
polarized entry and release of junin virus, a new world arenavirus.junin virus (junv), the causative agent of argentine haemorrhagic fever, is a human pathogen that naturally enters the body through the epithelial cells of the respiratory and digestive tracts. the interaction of junv with two types of polarized epithelial cultures, vero c1008 and a549, was investigated. radioactive virus-binding assays showed that junv infects polarized lines preferentially through the apical surface. high-level expression of viral nucleoprotein was detected in polarized cell l ...200515831960
basolateral entry and release of new and old world arenaviruses from human airway epithelia.transmission of arenaviruses from rodent hosts to humans is generally thought to occur through inhalation or ingestion of dust or droplets containing viral particles. here we demonstrate that two identified arenavirus receptors, alpha-dystroglycan (alpha-dg) and transferrin receptor 1 (tfr1), are expressed in polarized human airway epithelia. lymphocytic choriomeningitis virus strains with high or low alpha-dg affinity and junin virus, which binds tfr1, efficiently infected polarized epithelia o ...200818417570
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
junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type i ifn signaling.argentine hemorrhagic fever (ahf) is an endemo-epidemic disease caused by junín virus (junv), a member of the arenaviridae family. although a recently introduced live attenuated vaccine has proven to be effective, ahf remains a potentially lethal infection. like in other viral hemorrhagic fevers (vhf), ahf patients present with fever and hemorrhagic complications. although the causes of the bleeding are poorly understood, impaired hemostasis, endothelial cell dysfunction and low platelet counts ...201020419155
mice lacking alpha/beta and gamma interferon receptors are susceptible to junin virus infection.junin virus (junv) causes a highly lethal human disease, argentine hemorrhagic fever. previous work has demonstrated the requirement for human transferrin receptor 1 for virus entry, and the absence of the receptor was proposed to be a major cause for the resistance of laboratory mice to junv infection. in this study, we present for the first time in vivo evidence that the disruption of interferon signaling is sufficient to generate a disease-susceptible mouse model for junv infection. after per ...201020926559
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
argentine hemorrhagic fever vaccines.argentine hemorrhagic fever (ahf), an acute disease caused by junin virus (junv, arenaviridae), has been an important issue to public health in argentina since the early 1950s. the field rodent calomys musculinus is junv natural reservoir and human disease is a consequence of contact with infected rodents. a steady extention of ahf endemic area is being observed since the first reports of the disease. important achievements have been made in: (a) improvement of methods for the etiological diagno ...201121451263
the major determinant of attenuation in mice of the candid1 vaccine for argentine hemorrhagic fever is located in the g2 glycoprotein transmembrane domain.candid1, a live-attenuated junin virus vaccine strain, was developed during the early 1980s to control argentine hemorrhagic fever, a severe and frequently fatal human disease. six amino acid substitutions were found to be unique to this vaccine strain, and their role in virulence attenuation in mice was analyzed using a series of recombinant viruses. our results indicate that candid1 is attenuated in mice through a single amino acid substitution in the transmembrane domain of the g2 glycoprotei ...201121795336
host and viral traits predict zoonotic spillover from mammals.the majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, hiv, ebola and sars). understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. however, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species ...201728636590
endothelial cell function alteration after junin virus infection.hematologic involvement is the main feature of argentine hemorrhagic fever (ahf), an endemo-epidemic disease caused by junin virus (jv). since endothelial dysfunction could play a role in ahf-altered hemostasis, we studied human umbilical vein endothelial cell (huvec) infection with a virulent (jvv) and a non-virulent (jva) jv strain. cells were infected by the two jv variants with no detectable apoptosis or cytopathic effect. both viral variants up-regulated icam-1 and vcam-1 levels, while von ...200312888881
cytotoxicity and cytoadherence of human and murine polymorphonuclear leukocytes against junin virus infected targets in the absence of anti-viral antibody and complement.human and murine polymorphonuclear leukocytes (pmn) lysed l cells infected with junin virus (jv) in an in vitro system free of antiviral antibody and complement. infected vero cells proved to be resistant to the cytolytic effect. murine pmn showed an increased adherence on jv-infected l cells but did not attach to vero cells. the opposite was observed with human pmn, which did adhere to infected vero cells but not to infected l cells. these results indicate that pmn activity may be an early mech ...19911649909
ultrastructural and immunohistochemical studies in five cases of argentine hemorrhagic fever.ultrastructural and immunohistochemical studies on tissues from five patients with argentine hemorrhagic fever revealed previously undetected lesions caused by the viral infection. two types of particle were seen in the cells of all organs examined. the particles had some characteristics similar to those described for arenaviruses. however, the virus-like particles were intracellular, had a single membrane, and apparently originated by a process of budding into the endoplasmic reticulum cisterna ...197550390
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