Publications

endothelial cell permeability and adherens junction disruption induced by junín virus infection.	junín virus (junv) is endemic to the fertile pampas of argentina, maintained in nature by the rodent host calomys musculinus, and the causative agent of argentine hemorrhagic fever (ahf), which is characterized by vascular dysfunction and fluid distribution abnormalities. clinical as well as experimental studies implicate involvement of the endothelium in the pathogenesis of ahf, although little is known of its role. junv has been shown to result in productive infection of endothelial cells (ecs ...	2014	24710609
toll-like receptor 2-mediated innate immune responses against junín virus in mice lead to antiviral adaptive immune responses during systemic infection and do not affect viral replication in the brain.	successful adaptive immunity to virus infection often depends on the initial innate response. previously, we demonstrated that junín virus, the etiological agent responsible for argentine hemorrhagic fever (ahf), activates an early innate immune response via an interaction between the viral glycoprotein and toll-like receptor 2 (tlr2). here we show that tlr2/6 but not tlr1/2 heterodimers sense junín virus glycoprotein and induce a cytokine response, which in turn upregulates the expression of th ...	2014	24760892
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 ...	2014	24850726
potent inhibition of junín virus infection by interferon in murine cells.	the new world arenavirus junín virus (junv) is the causative agent of argentine hemorrhagic fever, a lethal human infectious disease. adult laboratory mice are generally resistant to peripheral infection by junv. the mechanism underlying the mouse resistance to junv infection is largely unknown. we have reported that interferon receptor knockout mice succumb to junv infection, indicating the critical role of interferon in restricting junv infection in mice. here we report that the pathogenic and ...	2014	24901990
rig-i enhanced interferon independent apoptosis upon junin virus infection.	junin virus (junv) is the etiological agent of argentine hemorrhagic fever (ahf), a human disease with a high case-fatality rate. it is widely accepted that arenaviral infections, including junv infections, are generally non-cytopathic. in contrast, here we demonstrated apoptosis induction in human lung epithelial carcinoma (a549), human hepatocarcinoma and vero cells upon infection with the attenuated candid#1 strain of, junv as determined by phosphatidylserine (ps) translocation, caspase 3 (ca ...	2014	24918927
reactive astrogliosis in response to hemorrhagic fever virus: microarray profile of junin virus-infected human astrocytes.	arenavirus junin is the causative agent of argentine hemorrhagic fever. limited information is available concerning the pathogenesis of this human disease, especially the pathogenesis of acute and late neurological symptoms.	2014	25015256
diseases of the central nervous system caused by lymphocytic choriomeningitis virus and other arenaviruses.		2014	25015511
[study of sensitivity of laboratory animals to a causative agent of argentine hemorrhagic fever].	study sensitivity of laboratory animals to a causative agent ofargentine hemorrhagic fever.	2014	25286529
[study of sensitivity of laboratory animals to a causative agent of argentine hemorrhagic fever].	study sensitivity of laboratory animals to a causative agent ofargentine hemorrhagic fever.	2014	25286529
inhibition of the pi3k/akt pathway by ly294002 does not prevent establishment of persistent junín virus infection in vero cells.	in previous work, we demonstrated that the arenavirus junín virus (junv) is able to activate akt by means of the phosphatidylinositol-3-kinase (pi3k) survival pathway during virus entry. this work extends our study, emphasizing the relevance of this pathway in the establishment and maintenance of persistent infection in vitro. during the course of infection, junv-infected vero cells showed a typical cytopathic effect that may be ascribed to apoptotic cell death. treatment of infected cultures wi ...	2015	25488290
research efforts to control highly pathogenic arenaviruses: a summary of the progress and gaps.	significant progress has been made in the past 10 years in unraveling the molecular biology of highly pathogenic arenaviruses that are endemic in several west african countries (lassa fever virus) and in some regions of south america (argentine and bolivian hemorrhagic fever viruses). while this has resulted in proof-of-concept studies of novel vaccine candidates in non-human primates and in the discovery of several novel antiviral small molecule drug candidates, none of them has been tested in ...	2015	25549822
sorting of small infectious virus particles by flow virometry reveals distinct infectivity profiles.	the nature and concentration of lipids and proteins at the surface of viruses are essential parameters for determining particle infectiveness. historically, averaged bulk analysis of viral particles has been the primary method to quantitatively investigate these parameters, though this neglects heterogeneity within populations. here we analyse the properties of junin virus particles using a sensitive flow virometry assay and further sort virions while conserving their infectiveness. this method ...	2015	25641385
the glycoprotein precursor gene of junin virus determines the virulence of the romero strain and the attenuation of the candid #1 strain in a representative animal model of argentine hemorrhagic fever.	the new world arenavirus junin virus (junv) is the causative agent of argentine hemorrhagic fever (ahf), a potentially deadly disease endemic to central regions of argentina. the live-attenuated candid #1 (can) strain of junv is currently used to vaccinate the human population at risk. however, the mechanism of attenuation of this strain is still largely unknown. therefore, the identification and functional characterization of viral genetic determinants dictating junv virulence or attenuation wo ...	2015	25810546
the glycoprotein precursor gene of junin virus determines the virulence of the romero strain and the attenuation of the candid #1 strain in a representative animal model of argentine hemorrhagic fever.	the new world arenavirus junin virus (junv) is the causative agent of argentine hemorrhagic fever (ahf), a potentially deadly disease endemic to central regions of argentina. the live-attenuated candid #1 (can) strain of junv is currently used to vaccinate the human population at risk. however, the mechanism of attenuation of this strain is still largely unknown. therefore, the identification and functional characterization of viral genetic determinants dictating junv virulence or attenuation wo ...	2015	25810546
the heterogeneous nuclear ribonucleoprotein k (hnrnp k) is a host factor required for dengue virus and junín virus multiplication.	heterogeneous nuclear ribonucleoproteins (hnrnps) are cellular factors involved in the replication of several viruses. in this study we analyzed the expression and intracellular localization of hnrnp a2 and hnrnp k in cell cultures infected with two viruses that cause human hemorrhagic fevers: dengue virus type 2 (denv-2) and junín virus (junv). we determined that denv-2 promoted the cytoplasmic translocation of hnrnp k and to a lesser extent of hnrnp a2, meanwhile, junv infection induced an inc ...	2015	25865411
human plasmacytoid dendritic cells elicited different responses after infection with pathogenic and nonpathogenic junin virus strains.	the arenavirus junin virus (junv) is the etiologic agent of argentine hemorrhagic fever. we characterized the junv infection of human peripheral blood-derived plasmacytoid dendritic cells (hpdc), demonstrating that hpdc are susceptible to infection with the c#1 strain (attenuated) and even more susceptible to infection with the p (virulent) junv strain. however, hpdc elicited different responses in terms of viability, activation, maturation, and cytokine expression after infection with both junv ...	2015	25926646
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 ...	2015	25926656
human hemorrhagic fever causing arenaviruses: molecular mechanisms contributing to virus virulence and disease pathogenesis.	arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (lcmv) to highly virulent hemorrhagic fever (hf) causing viruses such as lassa (lasv), junin (junv), machupo (macv), lujo (lujv), sabia (sabv), guanarito (gtov), and chapare (chpv), for which there are limited preventative and therapeutic measures. why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an e ...	2015	26011826
[sensitivity and specificity of the elisa kit for the detection of antidobies to junin virus].	the goal of this work was to describe methodological approaches to determination of sensitivity and specificity of the enzyme-linked immunosorbent assay kit (elisa kit) for detection of the specific anti-junin virus (jv) antibody. comparison of elisa to plaque reduction neutralization test (prnt) showed direct relationship between antibody titers in the samples of serum of immunized animals, determined by either prnt or elisa methods. the obtained results provided an opportunity to form the pane ...	2015	26021075
[sensitivity and specificity of the elisa kit for the detection of antidobies to junin virus].	the goal of this work was to describe methodological approaches to determination of sensitivity and specificity of the enzyme-linked immunosorbent assay kit (elisa kit) for detection of the specific anti-junin virus (jv) antibody. comparison of elisa to plaque reduction neutralization test (prnt) showed direct relationship between antibody titers in the samples of serum of immunized animals, determined by either prnt or elisa methods. the obtained results provided an opportunity to form the pane ...	2015	26021075
novel arenavirus entry inhibitors discovered by using a minigenome rescue system for high-throughput drug screening.	certain members of the arenaviridae family are category a agents capable of causing severe hemorrhagic fevers in humans. specific antiviral treatments do not exist, and the only commonly used drug, ribavirin, has limited efficacy and can cause severe side effects. the discovery and development of new antivirals are inhibited by the biohazardous nature of the viruses, making them a relatively poorly understood group of human pathogens. we therefore adapted a reverse-genetics minigenome (mg) rescu ...	2015	26041296
[new transmission scenarios of the argentine hemorrhagic fever since the introduction of the live attenuated junin virus vaccine (candid #1): an experience in migrant workers].	the argentine hemorrhagic fever (ahf) is a severe acute viral disease caused by the junin virus of the arenaviridae family. the ahf endemic area coincides geographically with the largest grain export agro-industrial complex of the country [argentina]. since the implementation of vaccination with the candid #1 vaccine, a significant reduction in incidence was achieved and risk patterns were modified. a previous study allowed characterizing these changes and identifying three transmission scenario ...	2015	26102120
tests in mice of a dengue vaccine candidate made of chimeric junin virus-like particles and conserved dengue virus envelope sequences.	two new vaccine candidates against dengue virus (denv) infection were generated by fusing the coding sequences of the self-budding z protein from junin virus (z-junv) to those of two cryptic peptides (z/denv-p1 and z/denv-p2) conserved on the envelope protein of all serotypes of denv. the capacity of these chimeras to generate virus-like particles (vlps) and to induce virus-neutralizing antibodies in mice was determined. first, recombinant proteins that displayed reactivity with a z-junv-specifi ...	2016	26386688
differential inhibition of macrophage activation by lymphocytic choriomeningitis virus and pichinde virus is mediated by the z protein n-terminal domain.	several arenavirus pathogens, such as lassa and junin viruses, inhibit macrophage activation, the molecular mechanism of which is unclear. we show that lymphocytic choriomeningitis virus (lcmv) can also inhibit macrophage activation, in contrast to pichinde and tacaribe viruses, which are not known to naturally cause human diseases. using a recombinant pichinde virus system, we show that the lcmv z n-terminal domain (ntd) mediates the inhibition of macrophage activation and immune functions.	2015	26423945
calcium regulation of hemorrhagic fever virus budding: mechanistic implications for host-oriented therapeutic intervention.	hemorrhagic fever viruses, including the filoviruses (ebola and marburg) and arenaviruses (lassa and junín viruses), are serious human pathogens for which there are currently no fda approved therapeutics or vaccines. importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. an important cellular sig ...	2015	26513362
superinfection exclusion is absent during acute junin virus infection of vero and a549 cells.	many viruses have evolved strategies of so-called "superinfection exclusion" to prevent re-infection of a cell that the same virus has already infected. although old world arenavirus infection results in down-regulation of its viral receptor and thus superinfection exclusion, whether new world arenaviruses have evolved such a mechanism remains unclear. here we show that acute infection by the new world junin virus (junv) failed to down-regulate the transferrin receptor and did not induce superin ...	2015	26549784
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 ...	2015	26581982
molecular basis for antibody-mediated neutralization of new world hemorrhagic fever mammarenaviruses.	in the western hemisphere, at least five mammarenaviruses cause human viral hemorrhagic fevers with high case fatality rates. junín virus (junv) is the only hemorrhagic fever virus for which transfusion of survivor immune plasma that contains neutralizing antibodies ("passive immunity") is an established treatment. here, we report the structure of the junv surface glycoprotein receptor-binding subunit (gp1) bound to a neutralizing monoclonal antibody. the antibody engages the gp1 site that binds ...	2015	26651946
low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.	favipiravir is approved in japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of rna viruses, including ebola. ribavirin is the only other licensed drug with activity against multiple rna viruses. recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. convalescent immune globulin is the only approved treatment for a ...	2016	26711718
low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.	favipiravir is approved in japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of rna viruses, including ebola. ribavirin is the only other licensed drug with activity against multiple rna viruses. recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. convalescent immune globulin is the only approved treatment for a ...	2016	26711718
the new world arenavirus tacaribe virus induces caspase-dependent apoptosis in infected cells.	the arenaviridae is a diverse and growing family of viruses that already includes more than 25 distinct species. while some of these viruses have a significant impact on public health, others appear to be non-pathogenic. at present little is known about the host cell responses to infection with different arenaviruses, particularly those found in the new world; however, apoptosis is known to play an important role in controlling infection of many viruses. here we show that infection with tacaribe ...	2016	26769540
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 ...	2016	26792737
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 ...	2016	26792737
identification and characterization of a novel broad-spectrum virus entry inhibitor.	virus entry into cells is a multistep process that often requires the subversion of subcellular machineries. a more complete understanding of these steps is necessary to develop new antiviral strategies. while studying the potential role of the actin network and one of its master regulators, the small gtpase cdc42, during junin virus (junv) entry, we serendipitously uncovered the small molecule zcl278, reported to inhibit cdc42 function as an entry inhibitor for junv and for vesicular stomatitis ...	2016	26912630
[experience of study and possible ways of elimination of false positive and false negative results during execution of polymerase chain reaction on an example of junin virus rna detection].	experience of study and possible ways of elimination of false positive and false negative results during execution of polymerase chain reaction on an example of junin virus rna detection. materialss and methods: junin virus--causative agent of argentine hemorrhagic fever (ahf) strain xjpr37/5787 was obtained from the state collection of pathogenicity group i causative agents of the 48th central research institute. reagent kit for detection of junin virus rna by rt-pcr was developed in the instit ...	2016	26950993
[experience of study and possible ways of elimination of false positive and false negative results during execution of polymerase chain reaction on an example of junin virus rna detection].	experience of study and possible ways of elimination of false positive and false negative results during execution of polymerase chain reaction on an example of junin virus rna detection. materialss and methods: junin virus--causative agent of argentine hemorrhagic fever (ahf) strain xjpr37/5787 was obtained from the state collection of pathogenicity group i causative agents of the 48th central research institute. reagent kit for detection of junin virus rna by rt-pcr was developed in the instit ...	2016	26950993
highly sensitive assay for measurement of arenavirus-cell attachment.	arenaviruses are a family of enveloped rna viruses that cause severe human disease. the first step in the arenavirus life cycle is attachment of viral particles to host cells. while virus-cell attachment can be measured through the use of virions labeled with biotin, radioactive isotopes, or fluorescent dyes, these approaches typically require high multiplicities of infection (moi) to enable detection of bound virus. we describe a quantitative (q)rt-pcr-based assay that measures junin virus stra ...	2016	26966937
monoclonal antibody therapy for junin virus infection.	countermeasures against potential biothreat agents remain important to us homeland security, and many of these pharmaceuticals could have dual use in the improvement of global public health. junin virus, the causative agent of argentine hemorrhagic fever (ahf), is an arenavirus identified as a category a high-priority agent. there are no food and drug administration (fda) approved drugs available for preventing or treating ahf, and the current treatment option is limited to administration of imm ...	2016	27044104
monoclonal antibody therapy for junin virus infection.	countermeasures against potential biothreat agents remain important to us homeland security, and many of these pharmaceuticals could have dual use in the improvement of global public health. junin virus, the causative agent of argentine hemorrhagic fever (ahf), is an arenavirus identified as a category a high-priority agent. there are no food and drug administration (fda) approved drugs available for preventing or treating ahf, and the current treatment option is limited to administration of imm ...	2016	27044104
novel strategies for development of hemorrhagic fever arenavirus live-attenuated vaccines.	several arenaviruses, chiefly lassa virus (lasv), cause hemorrhagic fever (hf) disease in humans and pose significant public health problems in their endemic regions. moreover, hf arenaviruses represent credible biodefense threats. there are not fda-approved arenavirus vaccines and current anti-arenaviral therapy is limited to an off-label use of ribavirin that is only partially effective.	2016	27118328
serologic evidence of mammarenaviruses among wild rodents in brazil.	we screened blood samples from 560 wild rodents collected in southeastern brazil for antibodies to a recombinant nucleoprotein (rn) of junín virus. six rodents were antibody positive (1.1%), demonstrating evidence of infection with mammarenaviruses in several species of brazilian rodents.	2016	27314481
myristoylation of the arenavirus envelope glycoprotein stable signal peptide is critical for membrane fusion but dispensable for virion morphogenesis.	arenaviruses are responsible for severe and often fatal hemorrhagic disease. in the absence of effective antiviral therapies and vaccines, these viruses pose serious threats to public health and biodefense. arenaviruses enter the host cell by fusion of the viral and endosomal membranes, a process mediated by the virus envelope glycoprotein gpc. unlike other class i viral fusion proteins, gpc retains its stable signal peptide (ssp) as an essential third subunit in the mature complex. ssp spans th ...	2016	27412594
structure-function relationship of the mammarenavirus envelope glycoprotein.	mammarenaviruses, including lethal pathogens such as lassa virus and junín virus, can cause severe hemorrhagic fever in humans. entry is a key step for virus infection, which starts with binding of the envelope glycoprotein (gp) to receptors on target cells and subsequent fusion of the virus with target cell membranes. the gp precursor is synthesized as a polypeptide, and maturation occurs by two cleavage events, yielding a tripartite gp complex (gpc) formed by a stable signal peptide (ssp), gp1 ...	2016	27562602
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 ...	2016	27580122
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 ...	2017	28100617
absence of an n-linked glycosylation motif in the glycoprotein of the live-attenuated argentine hemorrhagic fever vaccine, candid #1, results in its improper processing, and reduced surface expression.	junin virus (junv), a highly pathogenic new world arenavirus, is the causative agent of argentine hemorrhagic fever (ahf). the live-attenuated candid #1 (can) strain currently serves as a vaccine for at-risk populations. we have previously shown that the can glycoprotein (gpc) gene is the primary gene responsible for attenuation in a guinea pig model of ahf. however, the mechanisms through which the gpc contributes to the attenuation of the can strain remain unknown. a more complete understandin ...	2017	28220142
absence of an n-linked glycosylation motif in the glycoprotein of the live-attenuated argentine hemorrhagic fever vaccine, candid #1, results in its improper processing, and reduced surface expression.	junin virus (junv), a highly pathogenic new world arenavirus, is the causative agent of argentine hemorrhagic fever (ahf). the live-attenuated candid #1 (can) strain currently serves as a vaccine for at-risk populations. we have previously shown that the can glycoprotein (gpc) gene is the primary gene responsible for attenuation in a guinea pig model of ahf. however, the mechanisms through which the gpc contributes to the attenuation of the can strain remain unknown. a more complete understandin ...	2017	28220142
spatiotemporally restricted arenavirus replication induces immune surveillance and type i interferon-dependent tumour regression.	immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. new therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. here we show that the arenaviruses lymphocytic choriomeningitis virus (lcmv) and the clinically used junin virus vaccine (candid#1) preferentially replicate in tumour cells in a variety of murine and human c ...	2017	28248314
evaluation of cell viability dyes in antiviral assays with rna viruses that exhibit different cytopathogenic properties.	studies were conducted to determine the performance of four dyes in assessing antiviral activities of compounds against three rna viruses with differing cytopathogenic properties. dyes included alamarblue(®) measured by absorbance (alb-a) and fluorescence (alb-f), neutral red (nr), viral toxglo™ (vtg), and wst-1. viruses were chikungunya, dengue type 2, and junin, which generally cause 100, 80-90, and 50% maximal cytopathic effect (cpe), respectively, in vero 76. compounds evaluated were 6-azaur ...	2017	28359770
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
a map of the arenavirus nucleoprotein-host protein interactome reveals that junín virus selectively impairs the antiviral activity of double-stranded rna-activated protein kinase (pkr).	arenaviruses are enveloped negative-strand rna viruses that cause significant human disease. these viruses encode only four proteins to accomplish the viral life cycle, so each arenavirus protein likely plays unappreciated accessory roles during infection. here we used immunoprecipitation and mass spectrometry to identify human proteins that interact with the nucleoproteins (nps) of the old world arenavirus lymphocytic choriomeningitis virus (lcmv) and the new world arenavirus junín virus (junv) ...	2017	28539447
convergent immunological solutions to argentine hemorrhagic fever virus neutralization.	transmission of hemorrhagic fever new world arenaviruses from their rodent reservoirs to human populations poses substantial public health and economic dangers. these zoonotic events are enabled by the specific interaction between the new world arenaviral attachment glycoprotein, gp1, and cell surface human transferrin receptor (htfr1). here, we present the structural basis for how a mouse-derived neutralizing antibody (nab), od01, disrupts this interaction by targeting the receptor-binding surf ...	2017	28630325
enhanced protection against experimental junin virus infection through the use of a modified favipiravir loading dose strategy.	a collection of old and new world arenaviruses are etiologic agents of viral hemorrhagic fever, a syndrome that features hematologic abnormalities, vascular leak, hypovolemia, and multi-organ failure. treatment is limited to ribavirin for lassa fever and immune plasma for argentine hemorrhagic fever. improved therapeutic options that are safe, more effective and widely available are needed. here, we show that modification of favipiravir treatment to include a high-dose loading period achieves co ...	2017	28780425
enhanced protection against experimental junin virus infection through the use of a modified favipiravir loading dose strategy.	a collection of old and new world arenaviruses are etiologic agents of viral hemorrhagic fever, a syndrome that features hematologic abnormalities, vascular leak, hypovolemia, and multi-organ failure. treatment is limited to ribavirin for lassa fever and immune plasma for argentine hemorrhagic fever. improved therapeutic options that are safe, more effective and widely available are needed. here, we show that modification of favipiravir treatment to include a high-dose loading period achieves co ...	2017	28780425
highly pathogenic new world arenavirus infection activates the pattern recognition receptor pkr without attenuating virus replication in human cells.	the arenavirus family consists of several highly pathogenic viruses including the old world (ow) arenavirus lassa fever virus (lasv) and the new world (nw) junín virus (junv) and machupo virus (macv). host response to infection by these pathogenic arenaviruses is distinct in many aspects. nw junv and macv infections readily induce an ifn response in human cells, while ow lasv infection usually triggers an undetectable or weak ifn response. junv induces ifn response through rig-i, suggesting that ...	2017	28794024
description and characterization of a novel live-attenuated tri-segmented machupo virus in guinea pigs.	machupo virus (macv) is a member of the mammarenavirus genus, arenaviridae family and is the etiologic agent of bolivian hemorrhagic fever, which causes small outbreaks or sporadic cases. several other arenaviruses in south america junín virus (junv) in argentina, guanarito in venezuela, sabiá in brazil and chapare in bolivia, also are responsible for human hemorrhagic fevers. among these arenaviruses, junv caused thousands of human cases until 1991, when the live attenuated candid #1 vaccine, w ...	2018	29879985
effective population size differences in calomys musculinus, the host of junín virus: their relationship with the epidemiological history of argentine hemorrhagic fever.	argentine hemorrhagic fever (ahf) is a serious endemic disease in argentina, produced by junín virus, whose host is the sigmodontinae rodent calomys musculinus. within the endemic area, human incidence and proportion of infected rodents remains high for 5-10 years after the first appearance of the disease (epidemic [e] zone) and then gradually declines to sporadic cases (historic [h] zone). we tested the hypothesis that host populations within the e zone are large and well connected by gene flow ...	2018	29893205
[spatial difference in the incidence of argentine hemorrhagic fever and composition and abundance of rodents in the assemblage].	the argentine hemorrhagic fever (ahf) is a zoonotic disease endemic in a wide area of the humid pampa of argentina. the etiologic agent is the junin virus that is maintained in the wild by the rodent calomys musculinus and transmitted to humans, mainly, through aerosols generated from secretions and excretions.	2018	30534925
guinea pig transferrin receptor 1 mediates cellular entry of junín virus and other pathogenic new world arenaviruses.	several clade b new world arenaviruses (nwas) can cause severe and often fatal hemorrhagic fever, for which preventive and therapeutic measures are severely limited. these nwas use human transferrin receptor 1 (htfr1) as a host cell receptor for virus entry. the most prevalent of the pathogenic nwas is junín virus (junv), the etiological agent of argentine hemorrhagic fever. small animal models of junv infection are limited because most laboratory rodent species are refractory to disease. only g ...	2020	31748396
a single mutation (v64g) within the ring domain of z attenuates junin virus.	junin virus (junv) is a new world arenavirus that is the causative agent of argentine hemorrhagic fever (ahf). candid#1 (can) is a live-attenuated vaccine strain of junv that since its introduction has resulted in a marked decrease in ahf incidence within the endemic regions of the pampas in argentina. originally, the viral determinants and mechanisms of can attenuation were not well understood. recent work has identified the glycoprotein as the major attenuating factor for can. the establishmen ...	2020	32976538
development of a reverse genetic system to generate recombinant chimeric tacaribe virus that expresses junín virus glycoproteins.	mammarenaviruses are enveloped and segmented negative-stranded rna viruses that comprise several pathogenic members associated with severe human hemorrhagic fevers. tacaribe virus (tcrv) is the prototype for the new world group of mammarenaviruses and is not only naturally attenuated but also phylogenetically and antigenically related to all south american pathogenic mammarenaviruses, particularly the junín virus (junv), which is the etiological agent of argentinian hemorrhagic fever (ahf). more ...	2020	33203040
therapy for argentine hemorrhagic fever in nonhuman primates with a humanized monoclonal antibody.	the covid-19 pandemic has reemphasized the need to identify safe and scalable therapeutics to slow or reverse symptoms of disease caused by newly emerging and reemerging viral pathogens. recent clinical successes of monoclonal antibodies (mabs) in therapy for viral infections demonstrate that mabs offer a solution for these emerging biothreats. we have explored this with respect to junin virus (junv), an arenavirus classified as a category a high-priority agent and the causative agent of argenti ...	2021	33836604
second-generation live-attenuated candid#1 vaccine virus resists reversion and protects against lethal junín virus infection in guinea pigs.	live-attenuated virus vaccines are highly effective in preventing viral disease but carry intrinsic risks of residual virulence and reversion to pathogenicity. the classically derived candid#1 virus protects seasonal field workers in argentina against zoonotic infection by junín virus (junv) but is not approved in the united states, in part due to the potential for reversion at the attenuating locus, a phenylalanine-to-isoleucine substitution at position 427 in the gp2 subunit of the gpc envelop ...	2021	33952638
single dose rvsvδg-junvgp vaccine protects guinea pigs against lethal junin virus challenge.	junin virus (junv) is a pathogen of biodefense importance due to its potential for aerosol transmission and mortality rates reaching 30%. currently, there are no junv vaccines licensed by the united states food and drug administration (fda) for at-risk individuals. a vaccine based on recombinant vesicular stomatitis virus (rvsv) has been effectively used to prevent ebola virus disease in humans. here, we evaluated the protective efficacy of a rvsv expressing the junv glycoprotein (rvsvδg-junvgp) ...	2021	34373461