| 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 ... | 2008 | 18689636 |
| 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 ... | 2008 | 18692179 |
| 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 ... | 2008 | 18768973 |
| 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 ... | 2008 | 18771707 |
| 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 ... | 2008 | 18789362 |
| 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 ... | 2008 | 19040289 |
| 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 ... | 2009 | 19224989 |
| 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 ... | 2008 | 19278272 |
| 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 ... | 2008 | 19278272 |
| 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 ... | 2009 | 19321606 |
| 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 ... | 2009 | 19420075 |
| 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 ... | 2009 | 19442841 |
| 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 ... | 2009 | 19463727 |
| 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 ... | 2009 | 19548229 |
| 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- ... | 2009 | 19553554 |
| 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 ... | 2009 | 19591878 |
| 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 ... | 2009 | 19595723 |
| 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 ... | 2009 | 19625404 |
| 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 ... | 2009 | 19967131 |
| 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 ... | 2010 | 20007272 |
| 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 ... | 2010 | 20106925 |
| 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 ... | 2010 | 20148301 |
| 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 ... | 2010 | 20392854 |
| 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 ... | 2010 | 20419155 |
| 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 ... | 2010 | 20452431 |
| 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 ... | 2010 | 20452431 |
| [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 ... | 2010 | 20529769 |
| 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. | 2010 | 20563486 |
| 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 ... | 2010 | 20600335 |
| 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 ... | 2010 | 20652066 |
| 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 ... | 2010 | 20668086 |
| 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 ... | 2010 | 20706531 |
| 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 ... | 2010 | 20706531 |
| 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 ... | 2010 | 20839642 |
| 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 ... | 2010 | 20926559 |
| 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 ... | 2010 | 20980515 |
| 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 ... | 2010 | 21068387 |
| 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 ... | 2010 | 21115214 |
| 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 ... | 2010 | 21115797 |
| 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 ... | 2010 | 21123370 |
| 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 ... | 2010 | 21123388 |
| 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 ... | 2010 | 21123388 |
| 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 ... | 2010 | 21135183 |
| 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 ... | 2010 | 21159779 |
| 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. | 2011 | 21238601 |
| 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 ... | 2011 | 21451263 |
| 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 ... | 2011 | 21451263 |
| 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 ... | 2011 | 21572983 |
| medical microbiology | the hallmark of arenaviruses is their tendency to cause persistent silent infections in their natural hosts (rodents) and severe, often lethal, disseminated disease in humans. arenaviruses are pleomorphic enveloped particles that contain two rna segments of virus origin and ribosome-like components. suitable conditions for transmission of virus to humans occur in areas where humans come in contact with rodent urine that contains virus. persistent viremia and viruria in rodents result from a slow ... | 1996 | 21413313 |
| 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 ... | 2011 | 21632565 |
| 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 ... | 2011 | 21813702 |
| 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 ... | 2011 | 21795336 |
| 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 ... | 2011 | 21782004 |
| 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 ... | 2011 | 21689697 |
| 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, ... | 2011 | 21825302 |
| 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 ... | 2011 | 21957305 |
| 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 ... | 2011 | 21976641 |
| 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 ... | 2011 | 21880772 |
| 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 ... | 2011 | 21880772 |
| 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. | 2011 | 22022624 |
| [study of bone marrow in experimental argentine hemorrhagic fever. role of the megakaryocyte.] | in previous morphological studies on bone marrow of guinea pigs infected with junin virus, the coexistence of viral particles, antigens and cytopathic effects were observed in megakaryocytes. in addition, bone marrow is one of the organs where highest virus titers were obtained. however, although other myeloid cells presented intense cytopathic effect, viral antigens were observed only in reticular cells and virus particles were seen sporadically associated with immature cells. this study was de ... | 1980 | 22167697 |
| [study of bone marrow in experimental argentine hemorrhagic fever. role of the megakaryocyte.] | in previous morphological studies on bone marrow of guinea pigs infected with junin virus, the coexistence of viral particles, antigens and cytopathic effects were observed in megakaryocytes. in addition, bone marrow is one of the organs where highest virus titers were obtained. however, although other myeloid cells presented intense cytopathic effect, viral antigens were observed only in reticular cells and virus particles were seen sporadically associated with immature cells. this study was de ... | 1980 | 22167697 |
| Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative. | There are no specific approved drugs for the treatment of agents of viral hemorrhagic fevers (HF) and antiviral therapies against these viruses are urgently needed. The present study characterizes the potent and selective antiviral activity against the HF causing arenavirus Junin virus (JUNV) of the compound 10-allyl-6-chloro-4-methoxy-9(10H)-acridone, designated 3f. The effectiveness of 3f to inhibit JUNV multiplication was not importantly affected by the initial multiplicity of infection, with ... | 2012 | 22027649 |
| effect of ribavirin on junin virus infection in guinea pigs. | junin virus (junv) is the aetiological agent of argentine haemorrhagic fever. the pathogenesis of the infection is not well understood, no licensed vaccines exist and no specific antiviral therapy is available. previous studies have demonstrated the ability of ribavirin to delay and reduce junv disease and virus burden in guinea pigs without preventing death. based on available data, we performed three different studies to determine the efficacy of ribavirin against junv in the guinea pig model ... | 2012 | 22212688 |
| effect of ribavirin on junin virus infection in guinea pigs. | junin virus (junv) is the aetiological agent of argentine haemorrhagic fever. the pathogenesis of the infection is not well understood, no licensed vaccines exist and no specific antiviral therapy is available. previous studies have demonstrated the ability of ribavirin to delay and reduce junv disease and virus burden in guinea pigs without preventing death. based on available data, we performed three different studies to determine the efficacy of ribavirin against junv in the guinea pig model ... | 2012 | 22212688 |
| vaccine platforms to control arenaviral hemorrhagic fevers. | arenaviruses are rodent-borne emerging human pathogens. diseases caused by these viruses, e.g., lassa fever (lf) in west africa and south american hemorrhagic fevers (hfs), are serious public health problems in endemic areas. we have employed replication-competent and replication-deficient strategies to design vaccine candidates potentially targeting different groups "at risk". our leader lf vaccine candidate, the live reassortant vaccine ml29, is safe and efficacious in all tested animal models ... | 2012 | 23420494 |
| activity of a phenolic dibenzylsulfide against new world arenavirus infections. | background: junín virus (junv) and several other clade b new world arenaviruses cause human disease ranging from mild febrile illness to severe viral hemorrhagic fever (hf). these viruses pose a significant threat to national security and safe and effective therapies are limited outside of argentina, where immune plasma is the standard of care for treating junv infection in cases of argentine hf. methods: an in vitro screen of the chemtura library identified several compounds with activity again ... | 2012 | 23337126 |
| 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 |
| 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 |
| inhibition of arenavirus by a3, a pyrimidine biosynthesis inhibitor. | arenaviruses merit significant interest as important human pathogens, since several of them cause severe hemorrhagic fever disease that is associated with high morbidity and significant mortality. currently, there are no fda-licensed arenavirus vaccines available, and current antiarenaviral therapy is limited to an off-labeled use of the nucleoside analog ribavirin, which has limited prophylactic efficacy. the pyrimidine biosynthesis inhibitor a3, which was identified in a high-throughput screen ... | 2013 | 24198417 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| vaccination strategies against highly pathogenic arenaviruses: the next steps toward clinical trials. | vaccination is one of the most valuable weapons against infectious diseases and has led to a significant reduction in mortality and morbidity. however, for most viral hemorrhagic fevers caused by arenaviruses, no prophylactic vaccine is available. this is particularly problematic as these diseases are notoriously difficult to diagnose and treat. lassa fever is globally the most important of the fevers caused by arenaviruses, potentially affecting millions of people living in endemic areas, parti ... | 2013 | 23592977 |
| 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 ... | 2012 | 22629479 |
| 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 |
| sodium hydrogen exchangers contribute to arenavirus cell entry. | several arenaviruses, chiefly lassa virus (lasv), cause hemorrhagic fever (hf) disease in humans and pose a great public health concern in the regions in which they are endemic. moreover, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) is a neglected human pathogen of clinical significance. the limited existing armamentarium to combat human-pathogenic arenaviruses underscores the importance of developing novel antiarenaviral drugs ... | 2013 | 24173224 |
| an antibody recognizing the apical domain of human transferrin receptor 1 efficiently inhibits the entry of all new world hemorrhagic fever arenaviruses. | five new world (nw) arenaviruses cause human hemorrhagic fevers. four of these arenaviruses are known to enter cells by binding human transferrin receptor 1 (htfr1). here we show that the fifth arenavirus, chapare virus, similarly uses htfr1. we also identify an anti-htfr1 antibody, ch128.1, which efficiently inhibits entry mediated by the glycoproteins of all five viruses, as well as replication of infectious junín virus. our data indicate that all nw hemorrhagic fever arenaviruses utilize a co ... | 2012 | 22278244 |
| 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 |
| 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 |
| 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 |
| 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 |
| acridones as antiviral agents: synthesis, chemical and biological properties. | acridones are a class of compounds that have attracted attention in recent years for their wide range of biological properties, including selective inhibition of diverse human pathogenic viruses. the wide spectrum of antiviral activity includes dna and rna viruses, such as herpes simplex virus, cytomegalovirus, adenovirus, hepatitis c virus, dengue virus, and junin virus, among others, indicative of the involvement of cellular factors as potential targets of acridone derivatives. at the present, ... | 2013 | 23521684 |
| a host-oriented inhibitor of junin argentine hemorrhagic fever virus egress. | there are currently no u.s. food and drug administration (fda)-approved vaccines or therapeutics to prevent or treat argentine hemorrhagic fever (ahf). the causative agent of ahf is junin virus (junv); a new world arenavirus classified as a national institute of allergy and infectious disease/centers for disease control and prevention category a priority pathogen. the ptap late (l) domain motif within junv z protein facilitates virion egress and transmission by recruiting host tsg101 and other e ... | 2014 | 24522922 |
| 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 |
| diseases of the central nervous system caused by lymphocytic choriomeningitis virus and other arenaviruses. | | 2014 | 25015511 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |