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junín virus infection activates the type i interferon pathway in a rig-i-dependent manner.junín virus (junv), an arenavirus, is the causative agent of argentine hemorrhagic fever, an infectious human disease with 15-30% case fatality. the pathogenesis of ahf is still not well understood. elevated levels of interferon and cytokines are reported in ahf patients, which might be correlated to the severity of the disease. however the innate immune response to junv infection has not been well evaluated. previous studies have suggested that the virulent strain of junv does not induce ifn in ...201222629479
differential effect of acute and persistent junin virus infections on the nucleo-cytoplasmic trafficking and expression of heterogeneous nuclear ribonucleoproteins (hnrnps) type a/b.heterogeneous nuclear ribonucleoproteins a/b (hnrnps a/b), cellular rna-binding proteins that participate in splicing, trafficking, translation and turnover of mrnas, have been implicated in the life cycles of several rna cytoplasmic viruses. here we demonstrated that silencing of hnrnp a1 and a2 significantly reduced the replication of the arenavirus junin (junv), the etiological agent of argentine hemorrhagic fever. while acute junv infection did not modify total levels of hnrnp a/b expression ...201121632565
junin virus infection impairs stress granule formation in vero cells treated with arsenite via inhibition of eif2{alpha} phosphorylation.stress granules (sgs) are ephemeral cytoplasmic aggregates containing stalled translation preinitiation complexes involved in mrna storage and triage during the cell stress response. sg formation is triggered by the phosphorylation of the a subunit of eif2 (eif2a), which provokes a drastic blockage of protein translation. our results demonstrate that acute infection of vero cells with the arenavirus junin (junv), etiological agent of the argentine hemorrhagic fever, does not induce the formation ...201121813702
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
galectin-3 is upregulated in activated glia during junin virus-induced murine encephalitis.argentine haemorrhagic fever (ahf) is a systemic febrile syndrome characterized by several haematological and neurological alterations caused by junín virus (junv), a member of the arenaviridae family. newborn mice are highly susceptible to junv and the course of infection has been associated with the viral strain used. galectin-3 (gal-3) is an animal lectin that has been proposed to play an important role in some central nervous system (cns) diseases. in this study, we analysed gal-3 expression ...201121782004
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
development of peptide-conjugated morpholino oligomers as pan-arenavirus inhibitors.members of the arenaviridae are a threat to public health and can cause meningitis and hemorrhagic fever, yet treatment options remain limited by a lack of effective antivirals. in this study, we found that peptide-conjugated phosphorodiamidate morpholino oligomers (ppmo) complementary to viral genomic rna were effective in reducing arenavirus replication in cell cultures and in vivo. ppmo complementary to the jun+¡n virus genome were designed to interfere with viral rna synthesis, translation, ...201121825302
Molecular determinants of arenavirus Z protein homo-oligomerization and L polymerase binding.The arenavirus Z is a zinc-binding RING protein that has been implicated in multiple functions during the viral life cycle. These roles of Z involve interactions with viral and cellular proteins that remain incompletely understood. In this regard, Z inhibits viral RNA transcription and replication through direct interaction with the viral L polymerase. Here, we defined the L-binding domain of Tacaribe virus (TCRV) Z protein and the structural requirements mediating Z homo-oligomerization. By usi ...201121957305
Substitutions in the Glycoprotein (GP) of the Candid#1 Vaccine Strain of Junin Virus Increase Dependence on Human Transferrin Receptor 1 for Entry and Destabilize the Metastable Conformation of GP.Candid#1 (Cd1) is an attenuated vaccine strain of Junin virus, the causative agent of Argentine hemorrhagic fever. Although several substitutions are present in Cd1, their importance for attenuation has not been established. We functionally characterized the substitutions present in the Cd1 glycoprotein (GP) and identified F427I in the transmembrane domain of the GP2 subunit as reducing infectivity in a reconstituted viral system. We further showed that this phenotype derives from the destabiliz ...201121976641
junin virus infects mouse cells and induces innate immune responses.junín virus is the causative agent for argentine hemorrhagic fever, and its natural host is the new world rodent calomys musculinus. the virus is transmitted to humans by aerosolization, and it is believed that many of the clinical symptoms are caused by cytokines produced by sentinel cells of the immune system. here we used the junín virus vaccine strain candid 1 to determine whether mouse cells could be used to study virus entry and antiviral innate immune responses. we show that candid 1 can ...201121880772
junin virus infects mouse cells and induces innate immune responses.junín virus is the causative agent for argentine hemorrhagic fever, and its natural host is the new world rodent calomys musculinus. the virus is transmitted to humans by aerosolization, and it is believed that many of the clinical symptoms are caused by cytokines produced by sentinel cells of the immune system. here we used the junín virus vaccine strain candid 1 to determine whether mouse cells could be used to study virus entry and antiviral innate immune responses. we show that candid 1 can ...201121880772
Effective oral favipiravir (T-705) therapy initiated after the onset of clinical disease in a model of arenavirus hemorrhagic Fever.Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed.201122022624
junín virus. a xxi century update.junín virus of the arenaviridae family is the etiological agent of argentine hemorrhagic fever, a febrile syndrome causing hematological and neurological symptoms. we review historical perspectives of current knowledge on the disease, and update information related to the virion and its potential pathogenic mechanisms.201121238601
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
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
tacaribe virus but not junin virus infection induces cytokine release from primary human monocytes and macrophages.the mechanisms underlying the development of disease during arenavirus infection are poorly understood. however, common to all hemorrhagic fever diseases is the involvement of macrophages as primary target cells, suggesting that the immune response in these cells may be of paramount importance during infection. thus, in order to identify features of the immune response that contribute to arenavirus pathogenesis, we have examined the growth kinetics and cytokine profiles of two closely related ne ...201121572983
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
efficient budding of the tacaribe virus matrix protein z requires the nucleoprotein.the z protein has been shown for several arenaviruses to serve as the viral matrix protein. as such, z provides the principal force for the budding of virus particles and is capable of forming virus-like particles (vlps) when expressed alone. for most arenaviruses, this activity has been shown to be linked to the presence of proline-rich late-domain motifs in the c terminus; however, for the new world arenavirus tacaribe virus (tcrv), no such motif exists within z. it was recently demonstrated t ...201020106925
molecular analysis of the virulence attenuation process in junín virus vaccine genealogy.the junín virus strain candid#1 was developed as a live attenuated vaccine for argentine hemorrhagic fever. in this article, we report sequence information of the l and s rnas of junín virus candid#1 and xj#44 strains, and show the comparisons with the xj13 wild-type strain and with other junín virus strains, like romero, iv4454 and mc2 strains, and other closely and distantly related arenaviruses. comparisons of the nucleotide and amino acid sequences of all genes of three strains from the same ...201020148301
an antibody directed against the fusion peptide of junin virus envelope glycoprotein gpc inhibits ph-induced membrane fusion.the arenavirus envelope glycoprotein (gpc) initiates infection in the host cell through ph-induced fusion of the viral and endosomal membranes. as in other class i viral fusion proteins, this process proceeds through a structural reorganization in gpc in which the ectodomain of the transmembrane fusion subunit (g2) engages the host cell membrane and subsequently refolds to form a highly stable six-helix bundle structure that brings the two membranes into apposition for fusion. here, we describe ...201020392854
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
tc83 replicon vectored vaccine provides protection against junin virus in guinea pigs.junin virus (junv) is the etiological agent of the potentially lethal, reemerging human disease, argentine hemorrhagic fever (ahf). the mechanism of the disease development is not well understood and no antiviral therapy is available. candid 1, a live-attenuated vaccine, has been developed by the us army and is being used in the endemic area to prevent ahf. this vaccine is only approved for use in argentina. in this study we have used the alphavirus-based approach to engineer a replicon system b ...201020452431
tc83 replicon vectored vaccine provides protection against junin virus in guinea pigs.junin virus (junv) is the etiological agent of the potentially lethal, reemerging human disease, argentine hemorrhagic fever (ahf). the mechanism of the disease development is not well understood and no antiviral therapy is available. candid 1, a live-attenuated vaccine, has been developed by the us army and is being used in the endemic area to prevent ahf. this vaccine is only approved for use in argentina. in this study we have used the alphavirus-based approach to engineer a replicon system b ...201020452431
[candid#1 vaccine against argentine hemorrhagic fever produced in argentina. immunogenicity and safety].a clinical study in 946 human volunteers was done to compare candid #1 vaccine manufactured in argentina with the vaccine produced in usa that had been previously used. the efficacy was evaluated using immunogenicity measured by the detection of neutralizing antibodies as a subrogate marker. safety was evaluated comparing the rate of adverse events. both vaccines showed a comparable rate of seroconversion, slightly higher than the efficacy estimated from previous studies (95.5%). there were no s ...201020529769
standardization of an elisa test using a recombinant nucleoprotein from the junin virus as the antigen and serological screening for arenavirus among the population of nova xavantina, state of mato grosso.arenavirus hemorrhagic fever is a severe emerging disease.201020563486
inhibition of arenavirus infection by thiuram and aromatic disulfides.a selected group of aromatic disulfides, thiuram disulfides and thiosulfones, provided by the national cancer institute, were evaluated in vitro for their inhibitory activity against junin virus (junv), the causative agent of argentine hemorrhagic fever. the aromatic disulfides nsc4492 and nsc71033 and the thiuram disulfide nsc14560 were, respectively, the more potent virucidal and antiviral agents against junv, with inactivating concentration 50% (ic(50)) values of 0.2-0.5 microm for virucidal ...201020600335
expression and purification of z protein from junín virus.arenaviridae comprises 23 recognized virus species with a bipartite ssrna genome and an ambisense coding strategy. the virions are enveloped and include nonequimolar amounts of each genomic rna species, designated l and s, coding for four orfs (n, gpc, l, and z). the arenavirus junín (junv) is the etiological agent of argentine hemorrhagic fever, an acute disease with high mortality rate. it has been proposed that z is the functional counterpart of the matrix proteins found in other negative-str ...201020652066
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
proteomic analysis of pichindé virus infection identifies differential expression of prothymosin-alpha.the arenaviruses include a number of important pathogens including lassa virus and junin virus. presently, the only treatment is supportive care and the antiviral ribavirin. in the event of an epidemic, patient triage may be required to more effectively manage resources; the development of prognostic biomarker signatures, correlating with disease severity, would allow rational triage. using a pair of arenaviruses, which cause mild or severe disease, we analyzed extracts from infected cells using ...201020706531
proteomic analysis of pichindé virus infection identifies differential expression of prothymosin-alpha.the arenaviruses include a number of important pathogens including lassa virus and junin virus. presently, the only treatment is supportive care and the antiviral ribavirin. in the event of an epidemic, patient triage may be required to more effectively manage resources; the development of prognostic biomarker signatures, correlating with disease severity, would allow rational triage. using a pair of arenaviruses, which cause mild or severe disease, we analyzed extracts from infected cells using ...201020706531
virucidal activity and chemical composition of essential oils from aromatic plants of central west argentina.the essential oils of seven aromatic plants from central west argentina were isolated by steam distillation and analyzed by a gas chromatography/mass spectrometry technique. the oils were screened for cytotoxicity and in vitro inhibitory activity against herpes simplex virus type 1 (hsv-1), dengue virus type 2 (denv-2) and junin virus (junv). the oils showed a variable virucidal action according to the virus. junv was the least susceptible virus in comparison with hsv-1 and denv-2. the better re ...201020839642
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
reverse genetics generation of chimeric infectious junin/lassa virus is dependent on interaction of homologous glycoprotein stable signal peptide and g2 cytoplasmic domains.the arenaviridae are a diverse and globally distributed collection of viruses that are maintained primarily by rodent reservoirs. junin virus (junv) and lassa virus (lasv) can both cause significant outbreaks of severe and often fatal human disease throughout their respective areas of endemicity. in an effort to improve upon the existing live attenuated junv candid1 vaccine, we generated a genetically homogenous stock of this virus from cdna copies of the virus s and l segments by using a revers ...201020980515
structure of a zinc-binding domain in the junin virus envelope glycoprotein.arenaviruses cause acute hemorrhagic fevers with high mortality. entry of the virus into the host cell is mediated by the viral envelope glycoprotein, gpc. in contrast to other class i viral envelope glycoproteins, the mature gpc complex contains a cleaved stable signal peptide (ssp) in addition to the canonical receptor-binding (g1) and transmembrane fusion (g2) subunits. ssp is critical for intracellular transport of the gpc complex to the cell surface and for its membrane-fusion activity. pre ...201021068387
imidazo[2,1-b]thiazole carbohydrate derivatives: synthesis and antiviral activity against junin virus, agent of argentine hemorrhagic fever.herein, we describe the syntheses of 3,5-disubstituted imidazo[2,1-b]thiazole. the cyclization step was performed in two different conditions by using either thermal or microwave heating. comparing the results of both methodologies, we found that the microwave assistance is an improved alternative to obtain this family of heterocyclic compound. compounds were first evaluated for cytotoxicity in vero cells by mtt method and then, the antiviral activity was assayed by a virus yield inhibition assa ...201021115214
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
use of single-cycle infectious lymphocytic choriomeningitis virus to study hemorrhagic fever arenaviruses.several arenaviruses, chiefly lassa virus (lasv) and junin virus in west africa and argentina, respectively, cause hemorrhagic fever (hf) disease in humans that is associated with high morbidity and significant mortality. the investigation of antiviral strategies to combat hf arenaviruses is hampered by the requirement of biosafety level 4 (bsl-4) facilities to work with these viruses. these biosafety hurdles could be overcome by the use of recombinant single-cycle infectious arenaviruses. to ex ...201021123370
rescue from cloned cdnas and in vivo characterization of recombinant pathogenic romero and live-attenuated candid #1 strains of junin virus, the causative agent of argentine hemorrhagic fever disease.the new world arenavirus junin virus (junv) is the causative agent of argentine hemorrhagic fever (ahf), which is associated with high morbidity and significant mortality. several pathogenic strains of junv have been documented, and a highly attenuated vaccine strain (candid #1) was generated and used to vaccinate the human population at risk. the identification and functional characterization of viral genetic determinants associated with ahf and candid #1 attenuation would contribute to the elu ...201021123388
rescue from cloned cdnas and in vivo characterization of recombinant pathogenic romero and live-attenuated candid #1 strains of junin virus, the causative agent of argentine hemorrhagic fever disease.the new world arenavirus junin virus (junv) is the causative agent of argentine hemorrhagic fever (ahf), which is associated with high morbidity and significant mortality. several pathogenic strains of junv have been documented, and a highly attenuated vaccine strain (candid #1) was generated and used to vaccinate the human population at risk. the identification and functional characterization of viral genetic determinants associated with ahf and candid #1 attenuation would contribute to the elu ...201021123388
alkylated porphyrins have broad antiviral activity against hepadnaviruses, flaviviruses, filoviruses, and arenaviruses.we screened ∼2,200 compounds known to be safe in people for the ability to reduce the amount of virion-associated hepatitis b virus (hbv) dna in the culture medium of producer cells. these efforts led to the discovery of an alkylated porphyrin, chlorophyllide, as the compound that achieved the greatest reduction in signal. here we report that chlorophyllide directly and quantitatively disrupted hbv virions at micromolar concentrations, resulting in the loss of all detectable virion dna, without ...201021135183
a specific interaction of small molecule entry inhibitors with the envelope glycoprotein complex of the junín hemorrhagic fever arenavirus.arenaviruses are responsible for acute hemorrhagic fevers worldwide and are recognized to pose significant threats to public health and biodefense. small molecule compounds have recently been discovered that inhibit arenavirus entry and protect against lethal infection in animal models. these chemically distinct inhibitors act on the tripartite envelope glycoprotein (gpc) through its unusual stable signal peptide subunit to stabilize the complex against ph-induced activation of membrane fusion i ...201021159779
intersubunit interactions modulate ph-induced activation of membrane fusion by the junin virus envelope glycoprotein gpc.the mature arenavirus envelope glycoprotein gpc is a tripartite complex comprising a stable signal peptide (ssp) in addition to the receptor-binding (g1) and transmembrane fusion (g2) subunits. we have shown previously that ssp is a key element in gpc-mediated membrane fusion, and that gpc sensitivity to acidic ph is modulated in part through the lysine residue at position 33 in the ectodomain loop of ssp (j. york and j. h. nunberg, j. virol. 80:7775-7780, 2006). a glutamine substitution at this ...200919224989
efficient reverse genetics generation of infectious junin viruses differing in glycoprotein processing.the new world arenaviruses, junin, machupo, guanarito, sabia, and chapare, are associated with rapidly progressing severe hemorrhagic fever with a high rate of case fatality in various regions of south america. the threat of natural or deliberate outbreaks associated with these viruses makes the development of preventive or therapeutic measures important. here we describe a junin virus functional minigenome system and a reverse genetics system for production of infectious junin virus. this robus ...200919321606
the ring domain and the l79 residue of z protein are involved in both the rescue of nucleocapsids and the incorporation of glycoproteins into infectious chimeric arenavirus-like particles.arenaviruses, such as tacaribe virus (tacv) and its closely related pathogenic junin virus (junv), are enveloped viruses with a bipartite negative-sense rna genome that encodes the nucleocapsid protein (n), the precursor of the envelope glycoprotein complex (gp), the polymerase (l), and a ring finger protein (z), which is the driving force of arenavirus budding. we have established a plasmid-based system which allowed the successful packaging of tacv-like nucleocapsids along with z and gp of jun ...200919420075
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
characterization of junín virus particles inactivated by a zinc finger-reactive compound.our previous studies reported the inhibitory action against arenaviruses of antiretroviral zinc finger-reactive compounds provided by the national cancer institute (usa). these compounds were able to inactivate virions as well as to reduce virus yields from infected cells. here, the inactivation of the arenavirus junín (junv), agent of argentine hemorrhagic fever, by the aromatic disulfide nsc20625 was analyzed. the treatment of purified junv with this compound eliminated infectivity apparently ...200919463727
involvement of cellular proteins in junin arenavirus entry.junin arenavirus (junv) entry is dependent on clathrin-mediated pathways and it relies on the integrity of the actin cytoskeleton as well as the dynamics of microtubules. to determine the method of entry used by this human pathogen, we have demonstrated that in vero cells junv is trafficked via the cellular dynamin 2 (dyn2) endocytic pathway and it is dependent on the eps15 gtpase. in addition, we have shown that the virus travels through rab5-mediated early and rab7-mediated late endosomes in i ...200919548229
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
inhibition of junín virus replication by small interfering rnas.junín virus (junv), the etiological agent of the argentine hemorrhagic fever, has a single-stranded rna genome with ambisense expression which encodes for five proteins. in previous works we have demonstrated that the z arenavirus matrix protein represents an attractive target for antiviral therapy. with the aim of studying a new alternative therapeutic mechanism, four z-specific sirnas (z1- to z4-sirnas) were tested showing variable efficacy. the most effective inhibitor was z2-sirna targeted a ...200919591878
participation of the phosphatidylinositol 3-kinase/akt pathway in junín virus replication in vitro.in this paper we demonstrate that infection of cell cultures with the arenavirus junín (junv), agent of the argentine haemorrhagic fever, leads to the activation of pi3k/akt signalling pathway. phosphorylation of akt occurs early during junv infection of vero cells and is blocked by the pi3k inhibitor, ly294002. infection of cells with uv-irradiated junv redeemed the pattern of stimulation observed for infectious virus indicating that an early stage of multiplication cycle would be enough to tri ...200919595723
assembly of arenavirus envelope glycoprotein gpc in detergent-soluble membrane microdomains.the family arenaviridae includes a number of highly pathogenic viruses that are responsible for acute hemorrhagic fevers in humans. genetic diversity among arenavirus species in their respective rodent hosts supports the continued emergence of new pathogens. in the absence of available vaccines or therapeutic agents, the hemorrhagic fever arenaviruses remain a serious public health and biodefense concern. arenaviruses are enveloped virions that assemble and bud from the plasma membrane. in this ...200919625404
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
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
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
cellular entry of lymphocytic choriomeningitis virus.in contrast to most enveloped viruses that enter the host cell via clathrin-dependent endocytosis, the old world arenavirus lymphocytic choriomeningitis virus (lcmv) enters cells via noncoated vesicles that deliver the virus to endosomes, where ph-dependent membrane fusion occurs. here, we investigated the initial steps of lcmv infection. we found that the attachment of lcmv to its cellular receptor alpha-dystroglycan occurs rapidly and is not dependent on membrane cholesterol. however, subseque ...200818045945
treatment of argentine hemorrhagic fever.argentine hemorrhagic fever (ahf) is a rodent-borne illness caused by the arenavirus junin that is endemic to the humid pampas of argentina. ahf has had significant morbidity since its emergence in the 1950s, with a case-fatality rate of the illness without treatment between 15% and 30%. the use of a live attenuated vaccine has markedly reduced the incidence of ahf. present specific therapy involves the transfusion of immune plasma in defined doses of neutralizing antibodies during the prodromal ...200818054395
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
site 1 protease is required for proteolytic processing of the glycoproteins of the south american hemorrhagic fever viruses junin, machupo, and guanarito.the cellular proprotein convertase site 1 protease (s1p) has been implicated in the proteolytic processing of the glycoproteins (gps) of old world arenaviruses. here we report that s1p is also involved in the processing of the gps of the genetically more-distant south american hemorrhagic fever viruses guanarito, machupo, and junin. efficient cleavage of guanarito virus gp, whose protease recognition sites deviate from the reported s1p consensus sequence, indicates a broader specificity of s1p t ...200818400865
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
dehydroepiandrosterone, epiandrosterone and synthetic derivatives inhibit junin virus replication in vitro.in the present paper the in vitro antiviral activity of dehydroepiandrosterone (dhea), epiandrosterone (ea) and 16 synthetic derivatives against junin virus (junv) replication in vero cells was studied. dhea and ea caused a selective inhibition of the replication of junv and other members of the arenaviridae family such as pichinde virus and tacaribe virus. the compounds were not virucidal to cell-free junv. the impairment of viral replication was not due to an inhibitory effect of the steroids ...200818462821
different mechanisms of cell entry by human-pathogenic old world and new world arenaviruses.the old world arenavirus lassa virus (lasv) is the causative agent of severe viral hemorrhagic fever (vhf) in humans and is the most prevalent human pathogen among arenaviruses. the present study investigated the largely unknown mechanisms of cell entry of lasv, a process know to be mediated solely by the virus envelope glycoprotein (gp). to circumvent biosafety restrictions associated with the use of live lasv, we used reverse genetics to generate a recombinant variant of the prototypic arenavi ...200818508885
synthesis and evaluation of n-substituted acridones as antiviral agents against haemorrhagic fever viruses.in the present study, a series of n-substituted acridone derivatives was synthesized and evaluated against two haemorrhagic fever viruses (hfv).200818610557
pathogenesis of xj and romero strains of junin virus in two strains of guinea pigs.argentine hemorrhagic fever (ahf), a systemic infectious disease caused by infection with junin virus, affects several organs, and patients can show hematologic, cardiovascular, renal, or neurologic symptoms. we compared the virulence of two junin virus strains in inbred and outbred guinea pigs with the aim of characterizing this animal model better for future vaccine/antiviral efficacy studies. our data indicate that this passage of the xj strain is attenuated in guinea pigs. in contrast, the r ...200818689636
pathogenesis of xj and romero strains of junin virus in two strains of guinea pigs.argentine hemorrhagic fever (ahf), a systemic infectious disease caused by infection with junin virus, affects several organs, and patients can show hematologic, cardiovascular, renal, or neurologic symptoms. we compared the virulence of two junin virus strains in inbred and outbred guinea pigs with the aim of characterizing this animal model better for future vaccine/antiviral efficacy studies. our data indicate that this passage of the xj strain is attenuated in guinea pigs. in contrast, the r ...200818689636
synthesis and antiviral activity of azoles obtained from carbohydrates.herein we describe the synthesis of 1,2,4-triazolyl-3-thione;1,3,4-oxadiazole, and imidazo[2,1-b]thiazole derivatives from carbohydrates. the antiviral activity of these compounds was tested against dengue and junin virus (the etiological agent of argentine hemorrhagic fever). the 3-(p-bromobenzoyl)-5-(1,2-o-isopropylidene-3-o-methyl-alpha-d-xylofuranos-5-ulos-5-yl)imidazo[2,1-b]thiazole was able to inhibit the replication of both viruses in vero cells at concentration significantly lower than t ...200818692179
ph-induced activation of arenavirus membrane fusion is antagonized by small-molecule inhibitors.the arenavirus envelope glycoprotein (gpc) mediates viral entry through ph-induced membrane fusion in the endosome. this crucial process in the viral life cycle can be specifically inhibited in the new world arenaviruses by the small-molecule compound st-294. here, we show that st-294 interferes with gpc-mediated membrane fusion by targeting the interaction of the g2 fusion subunit with the stable signal peptide (ssp). we demonstrate that amino acid substitutions at lysine-33 of the junín virus ...200818768973
astrocyte response to junín virus infection.in a previous study of experimental murine encephalitis induced by junín virus (jv), an arenavirus, we showed increased expression of inos by unidentified cells, concomitant with the astrocyte reaction. the specific inhibition of inos was associated with greater mortality but lower astrocytosis, suggesting that the protective role of nitric oxide (no) synthesized by inos was related to enhanced astrocyte activation, representing a beneficial cellular response to virus-induced central nervous sys ...200818771707
involvement of cytoskeleton in junín virus entry.the early events in junín virus (junv) infection are not thoroughly understood. we have previously shown that junv enter cells by clathrin-mediated endocytosis. in this report we examine the role of microfilaments and microtubules during early virus infection. inhibitory effects of drugs affecting main cytoskeletal components on junv entry into vero cells were analyzed. drugs that disrupted microfilaments or stabilized microtubules inhibited early steps of virus entry. in contrast, drugs that st ...200818789362
argentine hemorrhagic fever diagnostic test based on recombinant junín virus n protein.junín arenavirus is the etiologic agent of argentine hemorrhagic fever. due to its morbidity and high mortality rate in untreated cases, this endemic disease is of mandatory report in argentina. secure and accurate diagnostic methods are needed for the epidemiological surveillance of the disease. current assays rely on antigens prepared from lysates of virus infected mammalian cells. the bio-safety issue related to the manipulation of large quantities of virus restricts such antigen production t ...200819040289
distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the junín virus envelope glycoprotein.the arenavirus envelope glycoprotein (gp-c) retains a cleaved and stable signal peptide (ssp) as an essential subunit of the mature complex. this 58-amino-acid residue peptide serves as a signal sequence and is additionally required to enable transit of the assembled gp-c complex to the golgi, and for ph-dependent membrane fusion activity. we have investigated the c-terminal region of the junín virus ssp to study the role of the cellular signal peptidase (spase) in generating ssp. site-directed ...200717045626
bitopic membrane topology of the stable signal peptide in the tripartite junín virus gp-c envelope glycoprotein complex.the stable signal peptide (ssp) of the gp-c envelope glycoprotein of the junín arenavirus plays a critical role in trafficking of the gp-c complex to the cell surface and in its membrane fusion activity. ssp therefore may function on both sides of the lipid membrane. in this study, we have investigated the membrane topology of ssp by confocal microscopy of cells treated with the detergent digitonin to selectively permeabilize the plasma membrane. by using an affinity tag to mark the termini of s ...200717267481
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
characterization of junin arenavirus cell entry.junín virus (junv) entry is conducted by receptor-mediated endocytosis. to explore the cellular entry mechanism of junv, inhibitory effects of drugs affecting the main endocytic pathways on junv entry into vero cells were analysed. compounds that impair clathrin-mediated endocytosis were shown to reduce virus internalization without affecting virion binding. in contrast, drugs that alter lipid-raft microdomains, impairing caveola-mediated endocytosis, were not able to block virus entry. to show ...200717485539
development of recombinant nucleoprotein-based diagnostic systems for lassa fever.diagnostic systems for lassa fever (lf), a viral hemorrhagic fever caused by lassa virus (lasv), such as enzyme immunoassays for the detection of lasv antibodies and lasv antigens, were developed using the recombinant nucleoprotein (rnp) of lasv (lasv-rnp). the lasv-rnp was expressed in a recombinant baculovirus system. lasv-rnp was used as an antigen in the detection of lasv-antibodies and as an immunogen for the production of monoclonal antibodies. the lasv-rnp was also expressed in hela cells ...200717634509
superinfection exclusion in bhk-21 cells persistently infected with junín virus.we characterized a persistently junín virus (junv)-infected bhk-21 cell line obtained by experimental infection with the xjcl3 strain. this cell line, named k3, produced low levels of virus in supernatants which were not influenced by the presence of defective interfering (di) particles after the first year of infection. k3 cells were able to exclude superinfection of the homologous junv and the antigenically related tacaribe virus (tcrv), whereas the non-related arenaviruses lymphocytic choriom ...200717872526
a novel zinc-binding domain is essential for formation of the functional junín virus envelope glycoprotein complex.the envelope glycoprotein of the junín arenavirus (gp-c) mediates entry into target cells through a ph-dependent membrane fusion mechanism. unlike other class i viral fusion proteins, the mature gp-c complex retains a cleaved, 58-amino-acid signal peptide (ssp) as an essential subunit, required both for trafficking of gp-c to the cell surface and for the activation of membrane fusion. ssp has been shown to associate noncovalently in gp-c via the cytoplasmic domain (ctd) of the transmembrane fusi ...200717928348
identification and characterization of potent small molecule inhibitor of hemorrhagic fever new world arenaviruses.category a arenaviruses as defined by the national institute of allergy and infectious diseases (niaid) are human pathogens that could be weaponized by bioterrorists. many of these deadly viruses require biosafety level-4 (bsl-4) containment for all laboratory work, which limits traditional laboratory high-throughput screening (hts) for identification of small molecule inhibitors. for those reasons, a related bsl-2 new world arenavirus, tacaribe virus, 67-78% identical to junín virus at the amin ...200616343651
genomic features of attenuated junín virus vaccine strain candidate.junin virus strain candid #1 was developed as a live attenuated vaccine for argentine haemorrhagic fever. in this paper, we report the nucleotide sequences of l rna of candid #1 and examine the relationship to its more virulent ancestors junin virus xj#44 and xj 13 (prototype) and other closely and distantly related arenaviruses. comparisons of the nucleotide and amino acid sequences of l and z genes of candid #1 and its progenitor strains revealed twelve point mutations in the l polypeptide tha ...200616525733
characterization of the cellular receptors for the south american hemorrhagic fever viruses junin, guanarito, and machupo.the new world arenaviruses junin, machupo, and guanarito are the causative agents of hemorrhagic fevers (hf) with high mortality in humans. the cellular receptor for old world arenaviruses and one subgroup of the new world arenaviruses (clade c) have been identified as alpha-dystroglycan (alpha-dg). in contrast, the receptor(s) of the south american hf viruses, which belong to the clade b new world arenaviruses, are currently unknown. to begin to characterize the cellular receptors used by these ...200616574183
role of the stable signal peptide and cytoplasmic domain of g2 in regulating intracellular transport of the junín virus envelope glycoprotein complex.enveloped viruses utilize the membranous compartments of the host cell for the assembly and budding of new virion particles. in this report, we have investigated the biogenesis and trafficking of the envelope glycoprotein (gp-c) of the junín arenavirus. the mature gp-c complex is unusual in that it retains a stable signal peptide (ssp) as an essential component in association with the typical receptor-binding (g1) and transmembrane fusion (g2) subunits. we demonstrate that, in the absence of ssp ...200616698999
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
immune response to vaccination against argentine hemorrhagic fever in an area where different arenaviruses coexist.neutralizing antibody (nt ab) titers to candid #1 (c#1) vaccine against argentine hemorrhagic fever were studied for 2 years post-vaccination in 330 volunteers, to assess whether the kinetics and/or magnitude of this immune response is modified by previous infection with the arena viruses junin (jun) and lymphocytic choriomeningitis (lcm). a total of 160 volunteers received c#1, distributed as follows: without detectable pre-infection with arenaviruses (n = 54); with pre-existing antibodies to j ...200616817762
role of the stable signal peptide of junín arenavirus envelope glycoprotein in ph-dependent membrane fusion.the envelope glycoprotein of the arenaviruses (gp-c) is unusual in that the mature complex retains the cleaved, 58-amino-acid signal peptide. association of this stable signal peptide (ssp) has been shown to be essential for intracellular trafficking and proteolytic maturation of the gp-c complex. we identify here a specific and previously unrecognized role of ssp in ph-dependent membrane fusion. amino acid substitutions that alter the positive charge at lysine k33 in ssp affect the ability of g ...200616840359
inhibition of cell fusion in junin virus-infected cells by sera from argentine hemorrhagic fever patients.junin virus (jv), a member of the arenaviridae family, is the etiological agent of argentine hemorrhagic fever (ahf). a low ph-pulse, induces fusion of vero cells infected with jv to form syncytia, whose production can be inhibited by neutralizing antibodies against the jv major glycoprotein.200515780806
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
evaluation of chemical and antiviral properties of essential oils from south american plants.the essential oils of seven aromatic plants from córdoba, san luis and san juan provinces (argentina) were isolated by steam distillation and analysed by a gas chromatography/mass spectrometry technique. the oils were screened for cytotoxicity and in vitro inhibitory activity against herpes simplex virus type 1 (hsv-1), dengue virus type 2 (denv-2) and junin virus (junv) by a virucidal test. the oils showed a variable virucidal action according to the virus. the better relationship between cytot ...200516130522
genetic analysis of heptad-repeat regions in the g2 fusion subunit of the junín arenavirus envelope glycoprotein.the g2 fusion subunit of the junín virus envelope glycoprotein gp-c contains two hydrophobic heptad-repeat regions that are postulated to form a six-helix bundle structure required for the membrane fusion activity of class i viral fusion proteins. we have investigated the role of these heptad-repeat regions and, specifically, the importance of the putative interhelical a and d position sidechains by using alanine-scanning mutagenesis. all the mutant glycoproteins were expressed and transported t ...200516169032
antiviral mode of action of a synthetic brassinosteroid against junin virus replication.the antiviral mode of action of the synthetic brassinosteroid (22s,23s)-3beta-bromo-5alpha,22,23-trihydroxystigmastan-6-one (6b) against junin virus replication in vero cells was investigated. time-related experiments showed that 6b mainly affects an early event of virus growth cycle. neither adsorption nor internalization of viral particles was the target of the inhibitory action. the analysis of the effect of 6b on viral rna synthesis demonstrated that the presence of the compound adversely af ...200516171877
[preclinical assay of candid #1 vaccine against argentine hemorrhagic fever made in argentina].candid #1 vaccine against argentine hemorrhagic fever produced in usa versus lots of the same vaccine made in argentina were compared in guinea pigs regarding safety, immunogenicity and protective efficacy against a challenge with pathogenic junin virus. lots no exp 3, 7a and 8a of argentine origin as well as lot tsi 5-1-92 from usa were inoculated in guinea pigs of 250-400 g in two consecutive assays. ten animals inoculated with saline performed as normal controls in each experiment. parameters ...200516193711
[preclinical assay of candid #1 vaccine against argentine hemorrhagic fever made in argentina].candid #1 vaccine against argentine hemorrhagic fever produced in usa versus lots of the same vaccine made in argentina were compared in guinea pigs regarding safety, immunogenicity and protective efficacy against a challenge with pathogenic junin virus. lots no exp 3, 7a and 8a of argentine origin as well as lot tsi 5-1-92 from usa were inoculated in guinea pigs of 250-400 g in two consecutive assays. ten animals inoculated with saline performed as normal controls in each experiment. parameters ...200516193711
recent range expansion and low levels of contemporary gene flow in calomys musculinus: its relationship with the emergence and spread of argentine haemorrhagic fever.the geographic distribution of haplotype diversity in the rodent calomys musculinus, sampled from 16 wild populations of argentina, was analysed on two geographical scales. the species is the natural reservoir of the junin virus, the etiological agent of the argentine haemorrhagic fever (ahf). in all, 24 composite haplotypes were recognised in the mtdna d-loop region. haplotypes 1 and 2, internal in the network, were the most frequent and were present in almost all populations. the absence of la ...200415316554
recent range expansion and low levels of contemporary gene flow in calomys musculinus: its relationship with the emergence and spread of argentine haemorrhagic fever.the geographic distribution of haplotype diversity in the rodent calomys musculinus, sampled from 16 wild populations of argentina, was analysed on two geographical scales. the species is the natural reservoir of the junin virus, the etiological agent of the argentine haemorrhagic fever (ahf). in all, 24 composite haplotypes were recognised in the mtdna d-loop region. haplotypes 1 and 2, internal in the network, were the most frequent and were present in almost all populations. the absence of la ...200415316554
the signal peptide of the junín arenavirus envelope glycoprotein is myristoylated and forms an essential subunit of the mature g1-g2 complex.arenaviruses comprise a diverse family of rodent-borne viruses that are responsible for recurring and emerging outbreaks of viral hemorrhagic fevers worldwide. the junín virus, a member of the new world arenaviruses, is endemic to the pampas grasslands of argentina and is the etiologic agent of argentine hemorrhagic fever. in this study, we have analyzed the assembly and function of the junín virus envelope glycoproteins. the mature envelope glycoprotein complex is proteolytically processed from ...200415367645
resistance to superinfection of vero cells persistently infected with junin virus.two non-virogenic vero cell lines persistently infected with the arenavirus junin (junv), named v3 and v7, were characterized with respect to their resistance to superinfection with homologous and antigenically related viruses. both lines were refractory to junv multiplication and partially resistant to other arenaviruses. junv was able to adsorb and penetrate persistently infected cells and, although v3 and v7 were able to support synthesis of antigenomic sense viral rna, protein production of ...200414991440
antiviral activity of antimicrobial cationic peptides against junin virus and herpes simplex virus.the in vitro antiviral activity of antimicrobial cationic peptides: cecropin a, melittin, magainin i and ii and indolicidin against the arenavirus junin virus (jv), and herpes simplex virus type 1 (hsv-1) and 2 (hsv-2) was evaluated. cecropin a effectively inhibited jv multiplication and failed to affect hsv replication whereas melittin impeded the multiplication of jv and hsv, but was highly toxic for the host cell. magainins i and ii exhibited inhibitory action toward hsv-1 and hsv-2 but were ...200415081088
intermediate filament integrity is required for junin virus replication.the role of the cytoskeletal framework in junin virus (junv) replication has already been demonstrated with compounds interfering with the microfilament (mf) and microtubule (mt) networks. in this work, we evaluated the role of intermediate filaments (if) during junv infection. we tested the effect of acrylamide, a compound that selectively disrupts if, in culture of three different cell types: vero cells, murine astrocytes and human foreskin fibroblasts. perturbation of intermediate filaments h ...200314550587
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
restricted gene flow in calomys musculinus (rodentia, muridae), the natural reservoir of junin virus.random amplified polymorphic dna polymerase chain reaction (rapd-pcr) markers were used to evaluate the relative contribution of gene flow as a determinant of the population genetic structure of the wild rodent calomys musculinus (the reservoir of argentine hemorrhagic fever [ahf]) in central argentina. one hundred eighty-seven individuals from 13 populations (9 of them from the endemic zone of ahf and 5 from areas outside it) were analyzed using 78 polymorphic rapd loci. genetic variation withi ...200314691315
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