cross-protection between tacaribe complex viruses. presence of neutralizing antibodies against junin virus (argentine hemorrhagic fever) in guinea pigs infected with tacaribe virus.cross-protection between junin virus and five other tacaribe complex viruses and the serological response of guinea pigs inoculated with tacaribe virus are reported here. previous infection with tamiami or pichinde viruses significantly delayed guinea pig deaths. a 58% survival rate was found among animals immunized with three doses of amapari virus, while guinea pigs inoculated with one dose of machupo or tacaribe virus were fully protected against junin virus. neutralization tests performed in ...1975178627
antigenic relationships of lymphocytic choriomeningitis virus and tacaribe virus in the indirect haemagglutination test.the indirect haemagglutination test has been developed for use with lcm and tacaribe viruses employing antibody-sensitized erythrocytes. both in this test and in the indirect haemagglutination inhibition test cross-reactions between lcm and tacaribe viruses were revealed. this opens new perspectives for group and species identification of arenaviruses.1975182398
experimental biology and pathogenesis of junin virus infection in animals and man.a fatal disease resembling argentine haemorrhagic fever of man has been produced in guinea-pigs and mice by inoculation with junin virus. infected guinea-pigs show macroscopic and microscopic haemorrhagic lesions, marked bone marrow changes, decreased leukocytes and platelets in the peripheral blood, and impairment of immunological response. this response permits differentiation between pathogenic (xj) and attenuated (xj cl(3)) strains. guinea-pigs inoculated with the xj cl(3) strain develop an ...1975182401
the circular, segmented nucleocapsid of an arenavirus-tacaribe virus.the nucleocapsid structures of tacaribe virus, a member of the arenaviridae, were purified from detergent-treated virus particles by equilibrium density gradient centrifugation. negative-contrast electron microscopy indicated that they were coiled, circular filaments. they had a mean diam. of 5 to 10 nm and two predominant length classes of 640 nm and 1300 nm were found.1977199698
serological evidence of infection of tacaribe virus and arboviruses in trinidadian bats.sera from 39 species of bats collected in trinidad between 1972 and 1974 were tested against some or all of 18 arboviruses in hemagglutination inhibition (hi) and/or suckling mouse neutralization (n) tests. a few sera were hi-positive with mucambo, eastern equine encephalitis (eee), oriboca, restan, manzanilla, guama, bimiti, and catu. no sera were hi-positive with mayaro, caraparu or maguari. many ser inhibited one or more of the group b hemagglutinins: ilheus, st. louis encephalitis (sle), den ...1978204207
temperature sensitivity of the arenavirus junin isolated from persistently infected vero cells.a persistently infected cell culture was established from vero cells surviving primary infection with wild-type junin virus (jvwt). the cells were refractory to superinfection by both junin virus and the related tacaribe virus. replication of virus released from the persistently infected cells (jvpi) was inhibited at 39 degrees. jvpi did not interfere with jvwt at 37 degrees, and it was inactivated at 37, 40, 43, 46 and 50 degrees much more rapidly than was jvwt.1979222707
molecular organization of junin virus s rna: complete nucleotide sequence, relationship with other members of the arenaviridae and unusual secondary this study, overlapping cdna clones covering the entire s rna molecule of junin virus, an arenavirus that causes argentine haemorrhagic fever, were generated. the complete sequence of this 3400 nucleotide rna was determined using the dideoxynucleotide chain termination method. the nucleocapsid protein (n) and the glycoprotein precursor (gpc) genes were identified as two non-overlapping open reading frames of opposite polarity, encoding primary translation products of 564 and 481 amino acids, ...19911654373
tacaribe arenavirus rna synthesis in vitro is primer dependent and suggests an unusual model for the initiation of genome replication.a tacaribe virus in vitro system for rna synthesis was established and found in large part to faithfully reproduce rna synthesis in vivo. similar to influenza virus and bunyavirus in vitro systems, this system was also highly dependent on added oligonucleotides. of the eight tested, only three were active, in the order gpc greater than cpg greater than apapc. determination of the 5' ends of the transcripts suggested that the oligonucleotides were acting as primers. in particular, whereas stimula ...19921738196
the 3' end termini of the tacaribe arenavirus subgenomic rnas.tacaribe virus (tv), a member of the arenaviridae family, contains two single-stranded rna genome segments called s and l. two proteins, in an ambisense coding strategy, are encoded in both the s rna and the l rna. the 3' ends of the tv four putative mrnas have been characterized using s1 nuclease mapping. the experiments revealed that the transcripts terminate within the intergenic region in each rna segment. no special sequences that might function as termination signals were evident. the 3' e ...19912024465
a novel mechanism for the initiation of tacaribe arenavirus genome replication.the ends of arenavirus genome and antigenome rnas are highly conserved and where determined directly, always contain a 3' g (referred to as position +1). however, primers extended to the 5' ends of tacaribe virus genomes and antigenomes extend to position -1. when genomes and antigenomes are annealed either inter or intramolecularly and treated with rnase a or t1, there appears to be a single unpaired g at the 5' ends of the hybrids. a single extra g is also found by cloning the 5' ends of s ant ...19902243392
nontemplated bases at the 5' ends of tacaribe virus mrnas.centrifugation of tacaribe arenavirus-infected cell extracts on cscl density gradients was used to separate genomes and antigenomes, which band at 1.31 g/ml as nucleocapsids, from mrnas which pellet. primer extensions on the banded rnas showed that the 5' ends of the genomes and antigenomes were unique, whereas primer extensions on the mrnas showed that their 5' ends were heterogenous in length, extending 0-4 bases beyond the 3' ends of the templates for their synthesis. this suggests that arena ...19902294647
synthesis of tacaribe virus polypeptides in an in vitro coupled transcription and translation system.we have analyzed polypeptides synthesized in a coupled in vitro transcription and translation system in response to detergent-disrupted tacaribe virus. analysis of the major tacaribe virus-specified product by two-dimensional polyacrylamide gel electrophoresis indicated that it had an isoelectric point similar to that of the tacaribe nucleocapsid polypeptide n; however, the in vitro product had an approximate mol. wt. of 73 000, compared to a mol. wt. of 68 000 for the n protein. the 73 000 dalt ...19852408399
properties and characterization of monoclonal antibodies to tacaribe virus.monoclonal antibodies prepared against tacaribe and junin viruses have been used to define further the serological relationships between arenaviruses of the tacaribe complex. a close relationship was found between these two viruses and the heterologous amapari and machupo viruses, with pichinde virus and parana virus being more distantly related. among the antibodies specific for tacaribe virus, five were found to react with viral antigens at the surface of infected cells and to neutralize virus ...19852410550
the 5' region of tacaribe virus l rna encodes a protein with a potential metal binding domain.we have just completed the tacaribe arenavirus (tv) genome structure by sequencing the 5' region of the l rna. analysis of the sequence has indicated the existence of an open reading frame (orf) in the viral sense rna encoding a 95 amino acid polypeptide. the first in phase aug codon is in positions 70-72 from the 5' end of the viral rna surrounded by a sequence favorable for the initiation of protein synthesis. the orf ends at positions 355-357. the predicted polypeptide (p11) contains a cystei ...19892510403
tacaribe virus l gene encodes a protein of 2210 amino acid residues.the nucleotide sequence of tacaribe virus (tv) l gene was obtained from two sets of overlapping cdna clones constructed by walking along the virus l rna using two successive synthetic dna primers. analysis of the sequence indicated the existence of a unique long open reading frame in the viral complementary strand. the first in-phase aug codon is in positions 31-33 from the 5' end of the viral complementary l rna surrounded by a sequence favorable for initiation of protein synthesis. the open re ...19892718387
tacaribe virus: a new alternative for argentine hemorrhagic fever vaccine.tacaribe virus is know to protect guinea pigs and primates against lethal challenge with junín virus. a long-term study on the effect of tacaribe virus infection in the guinea pig was carried out to determine the extent of cross-protection and whether antigen and/or viral persistence and tissue damage could be detected in immune animals. viral titers, antigen expression in organs, and histologic lesions were sequentially searched for up to 540 days postinfection (pi). neutralizing antibodies (ab ...19872828522
long-term protection against argentine hemorrhagic fever in tacaribe virus infected marmosets: virologic and histopathologic findings.tacaribe virus may represent a better alternative than attenuated strains of junin virus (jv) for immunization against argentine hemorrhagic fever (ahf) because of possible risk of persistent infection of disease associated with live, attenuated strains. callithrix jacchus marmosets, which suffer 100% mortality if inoculated with the pathogenic xj strain of jv, were used to evaluate possible tacaribe virus persistence, subclinical, or long-term disease and the duration of protection against chal ...19882832541
interactions of junin and tacaribe viruses during mixed infections.the interaction between junin virus (jv) and tacaribe virus (tacv) during mixed infections of rk13 cells was examined. the effects of a prior infection with jv upon tacv replication depended on the time between the two inoculations. simultaneous infection of rk13 cells with tacv and jv did not alter the plaquing efficiency of tacv; but if there was a 1- to 24-hour delay between jv preinfection and tacv superinfection, a variable increase of tacv replication was observed. the enhancement of tacv ...19852982755
abrogation of anti-pichinde virus cytotoxic t cell memory by cyclophosphamide and restoration by coinfection or interleukin 2.previously, we demonstrated that memory cell-mediated immune responses can be generated in pichinde virus (pv)-primed mice after secondary challenge in vivo with homologous virus. further, treatment of mice with cyclophosphamide (cy) before primary infection with pv abrogated the generation of h-2-restricted, virus-specific cytotoxic t lymphocytes (ctl), and rechallenge of these mice was followed by neither a primary nor a secondary ctl response. here, we demonstrate that this cy-induced block i ...19852989365
effect of tacaribe virus infection on host cell protein and nucleic acid synthesis.tacaribe virus stocks were prepared which induced definite lytic responses in vero cells infected at multiplicities giving synchronous infection. under these conditions, the first signs of cytopathic effect (c.p.e.) appeared at about 30 h post-infection and cell lysis occurred after 40 h. before the onset of cytopathic changes, the virus induced inhibition of host cell protein, dna and rna (primarily rrna) synthesis. these were designated c.p.e. (+) virus stocks. the effect of virus on host cell ...19852991438
vero cells persistently infected with tacaribe virus: role of interfering particles in the establishment of the infection.eight vero cell sublines (vero t) persistently infected with wild type tacaribe virus replicated in different hosts were established. in order to unravel the mechanism involved in the initiation and maintenance of persistence, the properties of virus shed by the sublines and the presence of interfering particles (ip) were analyzed. during the course of infection, persistent virus (tac-pi) underwent mutations although no consistent pattern of virus evolution was observed. ts mutants were isolated ...19863033931
molecular structure and early events in the replication of tacaribe arenavirus s rna.tacaribe arenavirus s rna was cloned and analysis of its nucleotide sequence revealed two open reading frames of significant size, one in the virus-sense strand, the other in the virus-complementary strand. the predicted amino acid sequences of the two reading frames were compared with the predicted primary structures of the nucleoprotein (n) and glycoprotein precursor (gpc) of lcm, pichinde and lassa viruses. the results indicated a high degree of homology between the proteins of similar proper ...19873617928
sensitivity of lymphocytic choriomeningitis and tacaribe viruses to several physical factors.a comparative study was performed as regards the behaviour of lymphocytic choriomeningitis virus (lcmv)--strains fo-2 and 522--and of tacaribe virus (strain tr 11573) at different temperatures and ph values. all the three arenavirus strains had a high thermosensitivity and were rapidly inactivated in an acid medium. lcmv was more sensitive to uv irradiation than tacaribe virus. the effect of sonication was also investigated.19863962179
influence of several chemical reagents on lymphocytic choriomeningitis and tacaribe viruses.the sensitivity of lymphocytic choriomeningitis virus (lcmv) and tacaribe virus to several chemical reagents was investigated. the viruses were sensitive to lipid solvents (ether, chloroform) and to detergents (sodium desoxycholate and triton x-100); they were rapidly inactivated by formalin, beta-propiolactone, hydrogen peroxide and chloramine b. the results obtained contribute to a more complete characterization of the biological features of the arenavirus group and may be useful for scientifi ...19863962180
tacaribe virus infection of the mouse: an immunopathologic disease model. 19744824325
tacaribe virus infection of guinea-pig. virus distribution, appearance of antibodies and immunity against junin virus infection. 19674970562
serological relationship of the tacaribe complex of viruses to lymphocytic choriomeningitis means of the indirect fluorescent-antibody test, cross serological reactivity was demonstrated between lymphocytic choriomeningitis (lcm) virus and the viruses of the tacaribe complex. antisera to all members of the tacaribe complex reacted with lcm virus; lcm antisera gave significant staining of amapari virus, but minimal or inconsistent reactions with tacaribe virus, and no reaction with two other viruses of the tacaribe complex. a low level cross-reaction was observed in complement fixati ...19704985595
detection of complement-fixing antibody after bolivian hemorrhagic fever, employing machupo, junín and tacaribe virus antigens. 19655840640
characterization of the tacaribe group of arboviruses. i. propagation and plaque assay of tacaribe virus in a line of african green monkey kidney cells (vero). 19676027511
[effect of the host cells in the crossed neutralization reactions between junín and tacaribe viruses ].it has been previously reported that guinea pigs inoculated with tacaribe virus grown in suckling mouse brain, develop specific anti-junín neutralizing antibodies (na) after 45 days of infection and a typical secondary response after junín virus challenge. since in these experiments both viruses were grown in suckling mouse brain doubt was raised about the specificity of na, considering the possibility that they were raised against host-cell antigens. in order to test this interpretation the fol ...19846101038
[optimal conditions for preserving the infectivity of tacaribe virus under various temperatures].the stability of tacaribe virus at different temperatures and the stabilizing effect of calf serum or human albumin were studied. the viral stock employed in this study was a 10% suckling mouse brain suspension prepared in phosphate buffer saline and fractionated in three aliquots: the first was supplemented with 0.5% human albumin, the second with 5% calf serum and the third was maintained without stabilizing agent. the infectivity of tacaribe virus kept at -70 degrees c was preserved during se ...19816101100
[experimental infection of guinea pigs with tacaribe virus: effect on the functioning of the immunocompetent system].tacaribe virus is the member most closely related to junín virus within the tacaribe complex. it has been demonstrated that both viruses are indistinguishable by complement-fixation, due to the high cross-reactivity. however, adult guinea pigs are highly sensitive to infection with the xj pathogenic strain of junín virus whereas tacaribe virus is nonpathogenic for this species. furthermore this last virus protects them against junín virus. the xj strain reduces the immune response of guinea pigs ...19816101101
nasal and intrathalamic inoculations of primates with tacaribe virus: protection against argentine hemorrhagic fever and absence of neurovirulence.callithrix jacchus marmosets were inoculated by different routes with two stocks of tacaribe virus, one from suckling mouse brain and another from human diploid mrc5 cells. all 12 primates inoculated by nasal route developed neutralizing serum antibodies without any clinical signs. all 6 primates receiving the mouse brain-tacaribe virus were protected against lethal challenge with pathogenic xj strain of junin virus, while protection was also conferred in 4 out of 6 primates receiving the diploi ...19846148851
protection of guinea pigs inoculated with tacaribe virus against lethal doses of junin virus.guinea pigs were protected against lethal doses of junin virus by a previous inoculation with tacaribe virus. fourteen guinea pigs were infected with 10(6) 50% lethal doses (ld50) of tacaribe virus and superinfected 45 days later with 10(3) ld50 of junin virus. appropriate control groups for both infections were also studied. the replication of junin virus was impaired, as no virus was isolated from blood and organs of animals killed on days 9 and 11 after infection. high levels of neutralizing ...19806245155
persistent infection of vero cells with tacaribe virus.persistently infected cultures have been established from vero cells surviving primary infection with tacaribe virus (vero-t). the growth rate and morphological characteristics of the persistently infected cells were indistinguishable from normal vero cells. virus release declined during the first 6 passages, a cyclical pattern was observed between passages 6 and 16, and subsequently no virus infectivity could be detected. co-cultivation with normal rk-13 or vero cells enhanced virus yield from ...19816271916
cross-protection in nonhuman primates against argentine hemorrhagic fever.the susceptibility of the marmoset callithrix jacchus to tacaribe virus infection was investigated to perform cross-protection studies between junin and tacaribe viruses. five marmosets inoculated with tacaribe virus failed to show any signs of disease, any alterations in erythrocyte, leukocyte, reticulocyte, and platelet counts or any changes in hematocrit or hemoglobin values. no tacaribe virus could be recovered from blood at any time postinfection. anti-tacaribe neutralizing antibodies appea ...19826276301
[immunization of guinea pigs against argentinian hemorrhagic fever with tacaribe virus replicated in human diploid cells]. 19816280018
response of cells persistently infected with arenaviruses to superinfection with homotypic and heterotypic viruses.vero cell cultures persistently infected with the arenaviruses junin, pichinde, tacaribe, and tamiami were established and designated vero-jun, vero-pic, vero-tac, and vero-tam, respectively. two types of carrier cultures could be easily distinguished: vero-jun and vero-tac systems were characterized by a lack of infectious virus production after a few cell transfers, whereas a more productive state with continuous release of virus was observed in vero-pic and vero-tam cultures. these difference ...19836312683
cosalane analogues with enhanced potencies as inhibitors of hiv-1 protease and integrase.several new analogues of the novel anti-hiv agent cosalane have been synthesized and evaluated as inhibitors of hiv-1 integrase and protease, hiv-1 replication, hiv-1 and hiv-2 cytopathicity, hiv-1- and hiv-2-mediated syncytium formation, and cytopathicity of a variety of human pathogenic viruses. the congeners displayed enhanced potencies relative to cosalane itself as inhibitors of hiv-1 integrase and protease. the two most potent analogues against hiv-1 integrase displayed ic50 values of 2.2 ...19957853337
antiviral activity of a sulphated polysaccharide from the red seaweed nothogenia fastigiata.the antiviral activity of polysaccharide fractions obtained from water extracts of the red seaweed nothogenia fastigiata was investigated. fraction f6, corresponding to a sulphated xylomannan, was found to inhibit efficiently the replication of herpes simplex virus type 1 (hsv-1). furthermore, f6 selectively inhibited the replication of several other enveloped viruses including herpes simplex virus type 2, human cytomegalovirus (hcmv), respiratory syncytial virus, influenza a and b virus, junin ...19948031312
the tacaribe arenavirus small zinc finger protein is required for both mrna synthesis and genome antiserum to a peptide of the tacaribe virus z protein was used to determine whether this small zn(2+)-binding protein was required for viral rna synthesis in infected cell extracts. specific immunodepletion of the extracts invariably reduced genome synthesis to near background levels, but strong effects on mrna synthesis occurred only early in the infection or when mrna synthesis was relatively weak. our results suggest that the z protein is required for both mrna and genome synthesis, but i ...19938419647
inhibition of arenavirus multiplication in vitro by phenotiazines.trifluoperazine (tfp) and chlorpromazine (cpz), two pharmacologically active phenotiazine derivatives, were evaluated for their inhibitory activity on the replication of the arenaviruses junin (jv), the etiological agent of argentine hemorrhagic fever, tacaribe virus and pichinde virus. both compounds achieved a concentration-dependent inhibition of viral multiplication at concentrations not affecting cell viability. the 50% inhibitory concentration (ic50) values determined by a virus yield inhi ...19968811199
immunological identification of tacaribe virus proteins.tacaribe virus (tv), an arenavirus, is an enveloped virus with genetic information encoded in two segments of single-stranded rna. the completed sequence of tv led to the identification of four open reading frames (orf). in order to establish a direct link between orfs in the sequence of tv and proteins present in virus particles and virus-infected cells, segments of the molecularly cloned tv genome were engineered so as to be expressed in escherichia coli to produce fusion proteins that were us ...19968837227
homologous and heterologous glycoproteins induce protection against junin virus challenge in guinea pigs.tacaribe virus (tacv) is an arenavirus that is genetically and antigenically closely related to junin virus (junv), the aetiological agent of argentine haemorrhagic fever (ahf). it is well established that tacv protects experimental animals fully against an otherwise lethal challenge with junv. to gain information on the nature of the antigens involved in cross-protection, recombinant vaccinia viruses were constructed that express the glycoprotein precursor (vv-gtac) or the nucleocapsid protein ...200010769070
antiviral and virucidal activities against arenaviruses of zinc-finger active compounds.fifteen antiretroviral zn-finger active compounds with diverse chemical structures, including azoic compounds, hydrazide derivatives, disulphide-based reagents and others were screened in vitro against junin virus (junv), the aetiological agent of argentine haemorrhagic fever, by a virus yield inhibition assay in vero cells. cytotoxicity was evaluated simultaneously by the mtt method. of the compounds, three were totally inactive as antivirals, nine presented moderate anti junv-activity and thre ...200010901294
transcription and rna replication of tacaribe virus genome and antigenome analogs require n and l proteins: z protein is an inhibitor of these processes.tacaribe virus (tv), the prototype of the new world group of arenaviruses, comprises a single phylogenetic lineage together with four south american pathogenic producers of hemorrhagic disease. the tv genome consists of two single-stranded rna segments called s and l. a reconstituted transcription-replication system based on plasmid-supplied tv-like rnas and tv proteins was established. plasmid expression was driven by t7 rna polymerase supplied by a recombinant vaccinia virus. plasmids were con ...200111711615
characterization of the arenavirus ring finger z protein regions required for z-mediated inhibition of viral rna synthesis.the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) is an enveloped virus with a bisegmented negative-strand rna genome whose proteomic capability is limited to four polypeptides, namely, nucleoprotein; surface glycoprotein (gp), which is proteolytically processed into gp1 and gp2; polymerase (l); and a small (11-kda) ring finger protein (z). using a reverse genetic system based on the arm strain of lcmv, we have previously shown that z has a strong inhibitory activity on lcmv mi ...200212050381
polysulfonates derived from metal thiolate complexes as inhibitors of hiv-1 and various other enveloped viruses in vitro.sodium 2-mercaptoethanesulfonate reacts with the metal ions pd(ii), pt(ii), ag(i), cd(ii) and zn(ii) to yield complexes containing multiple anionic sulfonate sites. on the basis of spectroscopic and other analytical data the complexes were assigned the tentative molecular formulas: pd6(sch2ch2so3na)12, ptn(sch2ch2so3na)2n+2, agn(sch2ch2so3na)n, na2zn4(sch2ch2so3na)10, and na2cd4(sch2ch2so3na)10. the complexes displayed a variety of differences in activity towards dna and rna viruses. the platinu ...200212448691
[immunization of guinea pigs against the junin virus by inoculation with tacaribe virus]. 196414168726
protection against junin virus by immunization with live tacaribe virus. 196514328956
thermolytic cpg-containing dna oligonucleotides as potential immunotherapeutic prodrugs.a cpg-containing dna oligonucleotide functionalized with the 2-(n-formyl-n-methyl)aminoethyl thiophosphate protecting group (cpg odn fma1555) was prepared from phosphoramidites 1a-d using solid-phase techniques. the oligonucleotide behaved as a prodrug by virtue of its conversion to the well-studied immunomodulatory cpg odn 1555 through thermolytic cleavage of the 2-(n-formyl-n-methyl)aminoethyl thiophosphate protecting group. such a conversion occurred at 37 degrees c with a half-time of 73 h. ...200515972797
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
effect of antilymphocyte serium on tacaribe virus infection in infant mice.tacaribe virus, a member of the arenovirus group, was demonstrated to have similarities in pathogenesis to the prototype virus of this group, lymphocytic choriomeningitis (lcm) virus. treatment with antilymphocyte serum (als) doubled the survival time of mice neonatally infected with a lethal dose of tacaribe virus. twenty-one per cent of als-treated infected animals survived more than 30 days. all animals had recoverable virus in brains and serum for the duration of life, and there was no diffe ...197116557996
a single stem-loop structure in tacaribe arenavirus intergenic region is essential for transcription termination but is not required for a correct initiation of transcription and replication.the genome of tacaribe virus (tv), prototype of the new world arenaviruses, comprises two rna segments each encoding two proteins in an ambisense orientation separated by an intergenic region (igr). we used a tv minireplicon system to investigate the nature of the igr structures required for transcription termination. we show that efficient generation of subgenomic (sg) rnas is related to a single hairpin structure comprising a stem with variable numbers of uninterrupted base pairs and stabilize ...200717125871
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
differential inhibition of type i interferon induction by arenavirus nucleoproteins.we have documented that the nucleoprotein (np) of the prototypic arenavirus lymphocytic choriomeningitis virus is an antagonist of the type i interferon response. in this study we tested the ability of nps encoded by representative arenavirus species from both old world and new world antigenic groups to inhibit production of interferon. we found that, with the exception of tacaribe virus (tcrv), all nps tested inhibited activation of beta interferon and interferon regulatory factor 3 (irf-3)-dep ...200717804508
arenaviruses.the arenaviridae family contains 22 recognized virus species, each of them strongly associated with a rodent species (except tacaribe virus which is associated with a species of bat), suggesting an ancient co-evolutionary process. although the concept of co-evolution between rodents and arenaviruses is now largely accepted, little has been uncovered in terms of dating the phenomenon and the mechanisms of evolution, including speciation and pathogenicity. these questions are targeted in the prese ...200717848068
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
rt-pcr assay for detection of lassa virus and related old world arenaviruses targeting the l gene.this study describes an rt-pcr assay targeting the l rna segment of arenaviruses. conserved regions were identified in the polymerase domain of the l gene on the basis of published sequences for lassa virus, lymphocytic choriomeningitis virus (lcmv), pichinde virus and tacaribe virus, as well as 15 novel sequences for lassa virus, lcmv, ippy virus, mobala virus and mopeia virus determined in this study. using these regions as target sites, a pcr assay for detection of all known old world arenavi ...200717905372
dehydroepiandrosterone, epiandrosterone and synthetic derivatives inhibit junin virus replication 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
mapping of the tacaribe arenavirus z-protein binding sites on the l protein identified both amino acids within the putative polymerase domain and a region at the n terminus of l that are critically involved in binding.tacaribe virus (tacv) is the prototype of the new world group of arenaviruses. the tacv genome encodes four proteins: the nucleoprotein (n), the glycoprotein precursor, the polymerase (l), and a ring finger protein (z). using a reverse genetics system, we demonstrated that tacv n and l are sufficient to drive transcription and replication mediated by tacv-like rnas and that z is a powerful inhibitor of these processes (lopez et al., j. virol. 65:12241-12251, 2001). more recently, we provided the ...200818799569
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
the z protein of the new world arenavirus tacaribe virus has bona fide budding activity that does not depend on known late domain motifs.the arenavirus small ring finger z protein has been shown to be the main driving force of budding for several arenaviruses. this z budding activity was found to be mediated by the late (l)-domain motifs p(t/s)ap and ppxy, located at the c terminus of z. here, we show that the z protein of tacaribe virus (tacv), a new world arenavirus, buds efficiently from cells despite lacking the canonical l-domain motifs p(t/s)ap and ppxy. likewise, potential l-domain motifs asap and ylcl present in tacv z di ...200919759156
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
interaction of silver nanoparticles with tacaribe virus.abstract:201020718972
development of a new tacaribe arenavirus infection model and its use to explore antiviral activity of a novel aristeromycin analog.a growing number of arenaviruses can cause a devastating viral hemorrhagic fever (vhf) syndrome. they pose a public health threat as emerging viruses and because of their potential use as bioterror agents. all of the highly pathogenic new world arenaviruses (nwa) phylogenetically segregate into clade b and require maximum biosafety containment facilities for their study. tacaribe virus (tcrv) is a nonpathogenic member of clade b that is closely related to the vhf arenaviruses at the amino acid l ...201020862280
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
identification of two functional domains within the arenavirus nucleoprotein.tacaribe virus (tcrv) belongs to the arenaviridae family. its bisegmented negative-stranded rna genome encodes the nucleoprotein (n), the precursor of the envelope glycoproteins, the polymerase (l), and a ring finger matrix (z) protein. the 570-amino-acid n protein binds to viral rna, forming nucleocapsids, which are the template for transcription and replication by the viral polymerase. we have previously shown that the interaction between n and z is required for assembly of infectious virus-li ...201021159858
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
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
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 ...201223337126
cd4 and cd8 t cells mediate distinct lethal meningoencephalitis in mice challenged with tacaribe arenavirus.neonates are at increased risk of viral encephalopathies that can result in neurological dysfunction, seizures, permanent disability and even death. the neurological damage results from the combined effect of the virus and the immune response it elicits, thus finding tools to facilitate viral clearance from central nervous system (cns) while minimizing neuron damage remains a critical challenge. neonatal mice inoculated intraperitoneally with tacaribe virus (tcrv) develop seizures, hindlimb para ...201627569560
transcriptome sequencing and annotation for the jamaican fruit bat (artibeus jamaicensis).the jamaican fruit bat (artibeus jamaicensis) is one of the most common bats in the tropical americas. it is thought to be a potential reservoir host of tacaribe virus, an arenavirus closely related to the south american hemorrhagic fever viruses. we performed transcriptome sequencing and annotation from lung, kidney and spleen tissues using 454 and illumina platforms to develop this species as an animal model. more than 100,000 contigs were assembled, with 25,000 genes that were functionally an ...201223166587
isolation of tacaribe virus, a caribbean arenavirus, from host-seeking amblyomma americanum ticks in florida.arenaviridae are a family of single stranded rna viruses of mammals and boid snakes. twenty-nine distinct mammalian arenaviruses have been identified, many of which cause severe hemorrhagic disease in humans, particularly in parts of sub-saharan africa, and in central and south america. humans typically become infected with an arenavirus through contact with excreta from infected rodents. tacaribe virus (tcrv) is an arenavirus that was first isolated from bats and mosquitoes during a rabies surv ...201425536075
n-alkyldeoxynojirimycin derivatives with novel terminal tertiary amide substitution for treatment of bovine viral diarrhea virus (bvdv), dengue, and tacaribe virus infections.novel n-alkyldeoxynojirimycins (nadnjs) with two hydrophobic groups attached to a nitrogen linker on the alkyl chain were designed. a novel nadnj containing a terminal tertiary carboxamide moiety was discovered that was a potent inhibitor against bvdv. further optimization resulted in a structurally more stable lead compound 24 with a submicromolar ec50 against bvdv, dengue, and tacaribe; and low cytotoxicity.201323453839
identification of novel 5,6-dimethoxyindan-1-one derivatives as antiviral agents.discovery of novel antiviral agents is essential because viral infection continues to threaten human life globally. various heterocyclic small molecules have been developed as antiviral agents. the 5,6-dimethoxy indan-1-one nucleus is of considerable interest as this ring is the key constituent in a range of bioactive compounds, both naturally occurring and synthetic, and often of considerable complexity.201728359234
sar analysis of a series of acylthiourea derivatives possessing broad-spectrum antiviral activity.a series of acylthiourea derivatives were designed, synthesized, and evaluated for broad-spectrum antiviral activity with selected viruses from poxviridae (vaccinia virus) and two different genera of the family bunyaviridae (rift valley fever and la crosse viruses). a compound selected from a library screen, compound 1, displayed submicromolar antiviral activity against both vaccinia virus (ec(50)=0.25 μm) and la crosse virus (ec(50)=0.27 μm) in cytopathic effect (cpe) assays. sar analysis was p ...201222664128
inhibition of a/human/hubei/3/2005 (h3n2) influenza virus infection by silver nanoparticles in vitro and in vivo.silver nanoparticles (agnps) have attracted much attention as antimicrobial agents and have demonstrated efficient inhibitory activity against various viruses, including human immunodeficiency virus, hepatitis b virus, and tacaribe virus. in this study, we investigated if agnps could have antiviral and preventive effects in a/human/hubei/3/2005 (h3n2) influenza virus infection. madin-darby canine kidney cells infected with agnp-treated h3n2 influenza virus showed better viability (p<0.05 versus ...201324204140
the new world arenavirus tacaribe virus induces caspase-dependent apoptosis in infected cells.the arenaviridae is a diverse and growing family of viruses that already includes more than 25 distinct species. while some of these viruses have a significant impact on public health, others appear to be non-pathogenic. at present little is known about the host cell responses to infection with different arenaviruses, particularly those found in the new world; however, apoptosis is known to play an important role in controlling infection of many viruses. here we show that infection with tacaribe ...201626769540
arenavirus infection induces discrete cytosolic structures for rna replication.arenaviruses are responsible for acute hemorrhagic fevers with high mortality and pose significant threats to public health and biodefense. these enveloped negative-sense rna viruses replicate in the cell cytoplasm and express four proteins. to better understand how these proteins insinuate themselves into cellular processes to orchestrate productive viral replication, we have identified and characterized novel cytosolic structures involved in arenavirus replication and transcription. in cells i ...201222875974
structures of arenaviral nucleoproteins with triphosphate dsrna reveal a unique mechanism of immune suppression.a hallmark of severe lassa fever is the generalized immune suppression, the mechanism of which is poorly understood. lassa virus (lasv) nucleoprotein (np) is the only known 3'-5' exoribonuclease that can suppress type i interferon (ifn) production possibly by degrading immune-stimulatory rnas. how this unique enzymatic activity of lasv np recognizes and processes rna substrates is unknown. we provide an atomic view of a catalytically active exoribonuclease domain of lasv np (lasv np-c) in the pr ...201323615902
arenavirus nucleoproteins prevent activation of nuclear factor kappa b.arenaviruses include several causative agents of hemorrhagic fever (hf) disease in humans that are associated with high morbidity and significant mortality. morbidity and lethality associated with hf arenaviruses are believed to involve the dysregulation of the host innate immune and inflammatory responses that leads to impaired development of protective and efficient immunity. the molecular mechanisms underlying this dysregulation are not completely understood, but it is suggested that viral in ...201222623788
tacaribe virus causes fatal infection of an ostensible reservoir host, the jamaican fruit bat.tacaribe virus (tcrv) was first isolated from 11 artibeus species bats captured in trinidad in the 1950s during a rabies virus surveillance program. despite significant effort, no evidence of infection of other mammals, mostly rodents, was found, suggesting that no other vertebrates harbored tcrv. for this reason, it was hypothesized that tcrv was naturally hosted by artibeus bats. this is in stark contrast to other arenaviruses with known hosts, all of which are rodents. to examine this hypothe ...201222379103
nonhuman transferrin receptor 1 is an efficient cell entry receptor for ocozocoautla de espinosa virus.ocozocoautla de espinosa virus (ocev) is a novel, uncultured arenavirus. we found that the ocev glycoprotein mediates entry into grivet and bat cells through transferrin receptor 1 (tfr1) binding but that ocev glycoprotein precursor (gpc)-pseudotyped retroviruses poorly entered 53 human cancer cell lines. interestingly, ocev and tacaribe virus could use bat, but not human, tfr1. replacing three human tfr1 amino acids with their bat ortholog counterparts transformed human tfr1 into an efficient o ...201324109228
identification of critical amino acids within the nucleoprotein of tacaribe virus important for anti-interferon activity.the arenavirus nucleoprotein (np) can suppress induction of type i interferon (ifn). this anti-ifn activity is thought to be shared by all arenaviruses with the exception of tacaribe virus (tcrv). to identify the tcrv np amino acid residues that prevent its ifn-countering ability, we created a series of np chimeras between residues of tcrv np and pichinde virus (picv) np, an arenavirus np with potent anti-ifn function. chimera np analysis revealed that a minimal four amino acid stretch derived f ...201323382389
regulation of tacaribe mammarenavirus translation: positive 5' and negative 3' elements and role of key cellular factors.mammarenaviruses are enveloped viruses with a bisegmented negative-stranded rna genome that encodes the nucleocapsid protein (np), the envelope glycoprotein precursor (gpc), the rna polymerase (l), and a ring matrix protein (z). viral proteins are synthesized from subgenomic mrnas bearing a capped 5' untranslated region (utr) and lacking 3' poly(a) tail. we analyzed the translation strategy of tacaribe virus (tcrv), a prototype of the new world mammarenaviruses. a virus-like transcript that carr ...201728468879
human transferrin receptor triggers an alternative tacaribe virus internalization pathway.tacaribe virus (tcrv) entry occurs by receptor-mediated endocytosis. to explore the entry mechanism used by tcrv, the inhibitory effects of drugs and dominant negative (dn) constructions affecting the main endocytic pathways were analyzed. in cells lacking the human transferrin receptor (htfr), compounds and dn proteins that impair clathrin-mediated endocytosis were shown to reduce virus internalization without affecting virion binding. in contrast, in cells expressing the htfr, compounds that a ...201626559962
differential contributions of tacaribe arenavirus nucleoprotein n-terminal and c-terminal residues to nucleocapsid functional activity.the arenavirus nucleoprotein (np) is the main protein component of viral nucleocapsids and is strictly required for viral genome replication mediated by the l polymerase. homo-oligomerization of np is presumed to play an important role in nucleocapsid assembly, albeit the underlying mechanism and the relevance of np-np interaction in nucleocapsid activity are still poorly understood. here, we evaluate the contribution of the new world tacaribe virus (tcrv) np self-interaction to nucleocapsid fun ...201424696466
vascular leak ensues a vigorous proinflammatory cytokine response to tacaribe arenavirus infection in ag129 mice.tacaribe virus (tcrv) is a less biohazardous relative of the highly pathogenic clade b new world arenaviruses that cause viral hemorrhagic fever syndromes and require handling in maximum containment facilities not readily available to most researchers. ag129 type i and ii interferon receptor knockout mice have been shown to be susceptible to tcrv infection, but the pathogenic mechanisms contributing to the lethal disease are unclear.201323816343
design and synthesis of n-alkyldeoxynojirimycin derivatives with improved metabolic stability as inhibitors of bvdv and tacaribe virus.novel n-alkyldeoxynojirimycins (nadnjs) based on our previous lead 3 were designed, synthesized and tested in metabolic assays and in virus cultures. nadnjs containing terminal tertiary benzamide, sulfonamide, urea, and oxazolidinone moieties were discovered to have improved metabolic stability compared to 3, while maintaining submicromolar ec50 against bvdv and tacaribe virus; and low cytotoxicity.201323747225
uncovering viral protein-protein interactions and their role in arenavirus life cycle.the arenaviridae family includes widely distributed pathogens that cause severe hemorrhagic fever in humans. replication and packaging of their single-stranded rna genome involve rna recognition by viral proteins and a number of key protein-protein interactions. viral rna synthesis is directed by the virus-encoded rna dependent-rna polymerase (l protein) and requires viral rna encapsidation by the nucleoprotein. in addition to the role that the interaction between l and the nucleoprotein may hav ...201223170177
tacaribe virus z protein interacts with the l polymerase protein to inhibit viral rna synthesis.tacaribe virus (tv) is the prototype of the new world group of arenaviruses. the tv genome encodes four proteins, the nucleoprotein (n), the glycoprotein precursor, the polymerase (l), and a small ring finger protein (z). using a reverse genetic system, we recently demonstrated that tv n and l are sufficient to drive transcription and full-cycle rna replication mediated by tv-like rnas and that z is a powerful inhibitor of these processes (n. lópez, r. jácamo, and m. t. franze-fernández, j. viro ...200312970423
tacaribe virus gene expression in cytopathic and non-cytopathic infections.tacaribe virus (tv) replication was compared in vero cells infected under conditions leading either to cell death (c.p.e.(+) infection) or to the establishment of persistence (c.p.e.(-) infection). to this end, two virus preparations were employed: one containing a ratio of standard (plaque-forming) viruses to interfering particles (ip) that would induce a distinct lytic response in vero cells infected at multiplicities giving synchronous infection and another virus stock enriched in ip that wou ...19948178447
analysis of the glycoprotein gene of tacaribe virus and neutralization-resistant variants.we have previously generated neutralization-resistant variants of tacaribe virus in the presence of a monoclonal antibody (mab) specific for the envelope glycoprotein. the envelope glycoprotein precursor (gpc) genes of two variant viruses were sequenced following polymerase chain reaction amplification of a specific region of the tacaribe virus s rna, and compared with the gpc gene of the parental virus. multiple nucleotide changes in the 3' half of the gpc gene were identified in the variants, ...19911875197
tacaribe virus infection may induce inhibition of the activity of the host cell ca2+ and na+/k+ pumps.infection of vero cells with tacaribe virus stocks containing a high ratio of standard (plaque-forming) viruses to defective interfering particles (dip) induced inhibition of the host cell ca2+ atpase (ca2+ pump) and the ouabain-sensitive na+/k+ atpase (na+/k+ pump). the mg2+ atpase which is not involved in cation transport was not affected. the presence of dip in the inocula protected the cells from alteration of the transport-associated atpases induced by standard viruses.19882833572
an antiviral factor from melia azedarach l. prevents tacaribe virus encephalitis in mice.treatment of neonatal mice with an antiviral factor, (avf), obtained from the leaves of melia azedarach l. protected them against lethal encephalitis caused by tacaribe virus inoculation. the degree of protection obtained varied from 66% to 100% depending on the virus dose. similarly, administration of avf to nursing mothers protected their offspring from developing virus encephalitis. avf does not directly inactivate tacaribe virus; it inhibits an early step (s) in the replication process in ce ...19863015669
analysis of polypeptides in tacaribe virus-infected cells.two virus-induced polypeptides designated p79 (mol wt, 79,000) and p105 (mol wt, 105,000) in bhk21 or vero cells infected with tacaribe (tac) virus have been identified. both polypeptides were found in immune precipitates with antiserum to tac virus, suggesting that they are virus specific. two-dimensional gel analysis of tac virus-infected vero cell extracts indicated that p79 and p105 were acidic proteins which did not comigrate with any polypeptides from uninfected cells. neither of the polyp ...19836310867
[interferon induction by tacaribe virus]. 19816168887
defective interfering tacaribe virus and persistently infected cells. 19807445428
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