TitleAbstractYear(sorted descending)
binding of equine infectious anemia virus rev to an exon splicing enhancer mediates alternative splicing and nuclear export of viral addition to facilitating the nuclear export of incompletely spliced viral mrnas, equine infectious anemia virus (eiav) rev regulates alternative splicing of the third exon of the tat/rev mrna. in the presence of rev, this exon of the bicistronic rna is skipped in a fraction of the spliced mrnas. in this report, the cis-acting requirements for exon 3 usage were correlated with sequences necessary for rev binding and transport of incompletely spliced rna. the presence of a purine-rich exon spli ...200010779344
transient kinetics of ligand binding and role of the c-terminus in the dutpase from equine infectious anemia virus.transient kinetics of the equine infectious anemia virus deoxyuridine 5'-triphosphate nucleotide hydrolase were characterized by monitoring the fluorescence of the protein. rate constants for the association and dissociation of substrate and inhibitors were determined and found to be consistent with a one-step mechanism for substrate binding. a c-terminal part of the enzyme presumed to be flexible was removed by limited trypsinolysis. as a result, the activity of the dutpase was completely quenc ...200010788633
development of a fluorescence polarization-based diagnostic assay for equine infectious anemia virus.the control of equine infectious anemia virus (eiav) infections of horses has been over the past 20 years based primarily on the identification and elimination of seropositive horses, predominantly by a standardized agar gel immunodiffusion (agid) assay in centralized reference laboratories. this screening for eiav-seropositive horses has been to date hindered by the lack of a rapid diagnostic format that can be easily employed in the field. we describe here the development of a rapid solution-p ...200010790112
immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus.persistent infection of equids by equine infectious anemia virus (eiav) is typically characterized by a progression during the first year postinfection from chronic disease with recurring disease cycles to a long-term asymptomatic infection that is maintained indefinitely. the goal of the current study was to perform a comprehensive longitudinal analysis of the course of virus infection and development of host immunity in experimentally infected horses as they progressed from chronic disease to ...200010846078
mutations occurring during serial passage of japanese equine infectious anemia virus in primary horse attenuated equine infectious anemia virus (eiav), named v26, was previously obtained after 50 passages of the japanese virulent strain v70 in primary macrophage culture. to clarify the differences between both viruses, their full-length sequences were determined. there were higher mutations in s2 (6.15% amino acid difference) and ltr (10.7% nucleotide difference). the presumed initiation codon of the s2 gene was absent from the sequence of v26. there was a large insertion within the long-term ...200010930666
characterization of the equine infectious anaemia virus s2 protein.s2 is an accessory protein of equine infectious anaemia virus (eiav), the function of which is unknown. in order to gain insight into the function of s2, the intracellular localization of the protein, its interaction with viral proteins and its incorporation into viral particles have been investigated. immunolocalization of s2 revealed punctate staining in the cytoplasm and the s2 protein co-precipitated with the eiav gag precursor. despite overexpression of s2 through the use of a codon-optimiz ...200010950976
general effect of sam68 on rev/rex regulated expression of complex retroviruses.we have previously demonstrated that overexpression of sam68 functionally substitutes for, as well as synergizes with, hiv-1 rev in rre-mediated gene expression and virus replication. in addition, c-terminal deletion mutants of sam68 exhibit a transdominant negative phenotype in hiv replication. we now report that sam68 also enhances the activities of rev-like proteins of other complex retroviruses (e.g. htlv-1 and eiav) on their respective rna targets. furthermore, we demonstrate that sam68 can ...200010962565
an in vitro transcription system that recapitulates equine infectious anemia virus tat-mediated inhibition of human immunodeficiency virus type 1 tat activity demonstrates a role for positive transcription elongation factor b and associated proteins in the mechanism of tat activation.equine infectious anemia virus (eiav) activates transcription via a tat protein, a tar element, and the equine elongation factor positive transcription elongation factor b (p-tefb). in human cells, eiav tat (etat) can inhibit the ability of human immunodeficiency virus type 1 (hiv-1) tat (htat) to activate transcription from the hiv-1 long terminal repeat, demonstrating that eiav tat can interact nonproductively with human p-tefb. to study the mechanism of eiav tat and hiv-1 tat activation, we d ...200010964778
antigenic drift of viruses within a host: a finite site model with demographic stochasticity.we theoretically study the antigenic drift of viruses within an infected host, as observed in human immunodeficiency virus (hiv) and equine infectious anemia virus (eiav) infections, assuming that a finite number of antigen-determining sites at the viral envelop gene are responsible for the specific immune response. the pattern of antigen evolution becomes more complex than that predicted from the previous one-dimensional antigen space models. if the viral growth rate is sufficiently large, the ...200011029069
equine infectious anaemia virus proteins with epitopes most frequently recognized by cytotoxic t lymphocytes from infected horses.efficacious lentiviral vaccines designed to induce cytotoxic t lymphocytes (ctl) in outbred populations with a diverse repertoire of mhc class i molecules should contain or express multiple viral proteins. to determine the equine infectious anaemia virus (eiav) proteins with epitopes most frequently recognized by ctl from seven horses infected for 0.5 to 7 years, retroviral vector-transduced target cells expressing viral proteins were used in ctl assays. gag p15 was recognized by ctl from 100% o ...200011038386
developments in preclinical aids vaccine efficacy models. 200011086857
the s2 gene of equine infectious anemia virus is a highly conserved determinant of viral replication and virulence properties in experimentally infected ponies.equine infectious anemia virus (eiav) is genetically one of the simplest lentiviruses in that the viral genome encodes only three accessory genes, tat, rev, and s2. although serological analyses demonstrate the expression of the s2 protein in persistently infected horses, the role of this viral gene remains undefined. we recently reported that the s2 gene is not essential for eiav replication in primary equine macrophages, as eiav mutants lacking the s2 gene replicate to levels similar to those ...200010590152
replication ability in vitro and in vivo of equine infectious anemia virus avirulent japanese attenuated equine infectious anemia virus (eiav), v26, was previously prepared by 50 passages of the japanese virulent strain v70 in primary horse macrophage culture. the horses inoculated with this v26 virus were shown to raise neutralizing antibodies against v70 without any viremia. here, we investigated the in vitro and in vivo replication ability of v26. comparison of the long-terminal repeat (ltr) sequences between v26 and v70 revealed a large insertion within the ltr u3 hypervariable re ...200010612667
interactions between equine cyclin t1, tat, and tar are disrupted by a leucine-to-valine substitution found in human cyclin t1.transcriptional transactivators (tat) from human immunodeficiency and equine infectious anemia viruses (hiv and eiav) interact with their transactivation response elements (tar) to increase the rates of viral transcription. whereas the human cyclin t1 is required for the binding of tat to tar from hiv, it is unknown how tat from eiav interacts with its tar. furthermore, tat from eiav functions in equine and canine cells but not in human cells. in this study, we present sequences of cyclins t1 fr ...200010623752
temperature inducible beta-sheet structure in the transactivation domains of retroviral regulatory proteins of the rev family.the interaction of the human immunodeficiency virus type 1 (hiv-1) regulatory protein rev with cellular cofactors is crucial for the viral life cycle. the hiv-1 rev transactivation domain is functionally interchangeable with analog regions of rev proteins of other retroviruses suggesting common folding patterns. in order to obtain experimental evidence for similar structural features mediating protein-protein contacts we investigated activation domain peptides from hiv-1, hiv-2, visna virus, fel ...199910629982
stable gene transfer to the nervous system using a non-primate lentiviral vector.we have constructed a non-primate lentiviral vector system based on the equine infectious anaemia virus (eiav). this system is able to transduce both dividing and non-dividing cells, including primary cultured hippocampal neurons and neurons and glia in the adult rat central nervous system (cns), at efficiencies comparable with hiv-based vectors. we demonstrate that the only eiav proteins required for this activity are gag/pol and that the only accessory protein required for vector production is ...199910602376
a particulate viral protein vaccine reduces viral load and delays progression to disease in immunized ponies challenged with equine infectious anemia virus.immunization regimens that induce a broadly reactive cytolytic t lymphocyte (ctl) response specific for lentiviral antigens have emerged as the leading candidates in efficacy trials conducted in both animal modelshumans. to date, lentivirus vaccination strategies have overlooked one such immunization strategy, namely the use of particulate antigens. to evaluate the efficacy of targeting antigen into the phagocytic pathway to elicit a cell-mediated immune response to lentiviral antigens, we initi ...19999927572
"hidden" dutpase sequence in human immunodeficiency virus type 1 gp120.a coding region homologous to the sequence for essential eukaryotic enzyme dutpase has been identified in different genomic regions of several viral lineages. unlike the nonprimate lentiviruses (caprine arthritis- encephalitis virus, equine infectious anemia virus, feline immunodeficiency virus, and visna virus), where dutpase is integrated into the pol coding region, this enzyme has never been demonstrated to be present in the primate lentivirus genomes (human immunodeficiency virus type 1 [hiv ...19999847382
crystal structure of dutpase from equine infectious anaemia virus; active site metal binding in a substrate analogue complex.the x-ray structures of dutpase from equine infectious anaemia virus (eiav) in unliganded and complexed forms have been determined to 1.9 and 2.0 a resolution, respectively. the structures were solved by molecular replacement using escherichia coli dutpase as search model. the exploitation of a relatively novel refinement approach for the initial model, combining maximum likelihood refinement with stereochemically unrestrained updating of the model, proved to be of crucial importance and should ...19999878436
model for lentivirus capsid core assembly based on crystal dimers of eiav p26.two crystal forms of recombinant p26 capsid protein (ca) from the equine infectious anemia virus (eiav) have in common an antiparallel four-helix bundle dimer interface between n-terminal domains (ntds). the dimer interface provides a lenient scaffold to accommodate the wide sequence variation in these helices within lentivirus ca. pairs of dimers weakly associate to form exact or approximate d2 symmetry tetramers. in one of the two crystal forms, the tetramers are linked via dimerization of c-t ...19999931251
identification of retroviral late domains as determinants of particle size.retroviral gag proteins, in the absence of any other viral products, induce budding and release of spherical, virus-like particles from the plasma membrane. gag-produced particles, like those of authentic retrovirions, are not uniform in diameter but nevertheless fall within a fairly narrow distribution of sizes. for the human immunodeficiency virus type 1 (hiv-1) gag protein, we recently reported that elements important for controlling particle size are contained within the c-terminal region of ...19999971814
photoactivated virucidal properties of tridentate 2,2'-dihydroxyazobenzene and 2-salicylideneaminophenol platinum pyridine complexes.the potent photoactivated virucidal activity of tridentate 2,2'-dihydroxyazobenzene- and 2-salicylideneaminophenol platinum pyridine complexes 1, 2, 4, 6, 7, 9, and 10 against enveloped viruses (e.g., eiav, hiv, and hsv) is described.199910021936
detection and induction of equine infectious anemia virus-specific cytotoxic t-lymphocyte responses by use of recombinant retroviral vectors.cytotoxic t lymphocytes (ctl) appear to be critical in resolving or reducing the severity of lentivirus infections. retroviral vectors expressing the gag/pr or su protein of the lentivirus equine infectious anemia virus (eiav) were constructed and used to evaluate eiav-specific ctl responses in horses. three promoters, cytomegalovirus, simian virus sv40, and moloney murine sarcoma virus (momsv) long terminal repeat (ltr), were used, and there was considerable variation in their ability to direct ...199910074123
reduction of cd4+ and cd8+ t lymphocytes during febrile periods in horses experimentally infected with equine infectious anemia virus.three horses were experimentally infected with equine infectious anemia virus (eiav). all horses were febrile after inoculation with eiav and then developed chronic symptoms with intermittent fever. the febrile period was characterized by a rise in body temperature with reduced pbl and erythrocyte counts. flow cytometric analysis showed that the reduced number of lymphocytes was due to significant decreases in cd4+ and cd8+ t cells in the absence of any change in b cell number. at the end of the ...199910077419
increased interleukin-6 activity in the serum of ponies acutely infected with equine infectious anaemia ponies were infected with the virulent wild-type wyoming strain of equine infectious anaemia virus (eiav). infection status was monitored by serum reverse transcriptase activity, rectal temperature, and complete blood count. preinfection serum and serum obtained during the initial febrile episode following infection were assayed for interleukin 6 (il-6) activity. postinfection il-6 activity was significantly increased as compared to preinfection values. the magnitude of increase in il-6 wa ...199910088717
characterization of (+) strand initiation and termination sequences located at the center of the equine infectious anemia virus genome.permeabilized preparations of equine infectious anemia virus (eiav) are shown here to support efficient and accurate synthesis of full-length double-stranded proviral dna. when (-) and (+) strand products were analyzed by southern blotting, a discontinuity, mapping approximately to the center of the eiav genome, could be demonstrated for the (+) strand, predicting a second site for initiation of dna synthesis and a specific mechanism of (+) strand termination. precise localization of this (+) st ...199910090753
long terminal repeat sequences of equine infectious anaemia virus are a major determinant of cell tropism.the wyoming strain of equine infectious anaemia virus (eiav) is a highly virulent field strain that replicates to high titre in vitro only in primary equine monocyte-derived macrophages. in contrast, wyoming-derived fibroblast-adapted eiav strains (malmquist virus) replicate in primary foetal equine kidney and equine dermis cells as well as in the cell lines fea and cf2th. wyoming and malmquist viruses differ extensively both in long terminal repeat (ltr) and envelope region sequences. we have c ...199910092016
gag protein epitopes recognized by cd4(+) t-helper lymphocytes from equine infectious anemia virus-infected carrier horses.antigen-specific t-helper (th) lymphocytes are critical for the development of antiviral humoral responses and the expansion of cytotoxic t lymphocytes (ctl). identification of relevant th lymphocyte epitopes remains an important step in the development of an efficacious subunit peptide vaccine against equine infectious anemia virus (eiav), a naturally occurring lentivirus of horses. this study describes th lymphocyte reactivity in eiav carrier horses to two proteins, p26 and p15, encoded by the ...199910196322
platelets from thrombocytopenic ponies acutely infected with equine infectious anemia virus are activated in vivo and hypofunctional.thrombocytopenia is a consistent finding and one of the earliest hematological abnormalities in horses acutely infected with equine infectious anemia virus (eiav), a lentivirus closely related to human immunodeficiency virus. multifactorial mechanisms, including immune-mediated platelet destruction and impaired platelet production, are implicated in the pathogenesis of eiav-associated thrombocytopenia. this study was undertaken to investigate whether regenerative thrombopoiesis and platelet dest ...199910364485
highly divergent lentiviral tat proteins activate viral gene expression by a common mechanism.the human immunodeficiency virus type 1 (hiv-1) tat protein (htat) activates transcription initiated at the viral long terminal repeat (ltr) promoter by a unique mechanism requiring recruitment of the human cyclin t1 (hcyct1) cofactor to the viral tar rna target element. while activation of equine infectious anemia virus (eiav) gene expression by the eiav tat (etat) protein appears similar in that the target element is a promoter proximal rna, etat shows little sequence homology to htat, does no ...199910373508
in vitro antibody-dependent enhancement assays are insensitive indicators of in vivo vaccine enhancement of equine infectious anemia virus.we have previously demonstrated a high propensity for enhancement of virus replication and disease resulting from experimental immunization of ponies with a baculovirus recombinant envelope (rgp90) vaccine from equine infectious anemia virus (eiav). the current studies were undertaken to examine the correlation between the observed in vivo vaccine enhancement and in vitro assays for antibody-dependent enhancement (ade) of eiav replication. toward this goal an optimized eiav in vitro enhancement ...199910388665
solution structure of the capsid protein from the human t-cell leukemia virus type-i.the solution structure of the capsid protein (ca) from the human t-cell leukemia virus type one (htlv-i), a retrovirus that causes t-cell leukemia and htlv-i-associated myelopathy in humans, has been determined by nmr methods. the protein consists of independent n and c-terminal domains connected by a flexible linker. the domains are structurally similar to the n-terminal "core" and c-terminal "dimerization" domains, respectively, of the human immunodeficiency virus type one (hiv-1) and equine i ...199910438634
effect of substrate residues on the p2' preference of retroviral proteinases.the substrate sequence requirements for preference toward p2' glu residue by human immunodeficiency virus type 1 (hiv-1) proteinase were studied in both the matrix protein/ capsid protein (ma/ca) and ca/p2 cleavage site sequence contexts. these sequences represent typical type 1 (-aromatic*pro-) and type 2 (-hydrophobic* hydrophobic-) cleavage site sequences, respectively. while in the type 1 sequence context, the preference for p2' glu over ile or gln was found to be strongly dependent on the i ...199910491141
natural variation of equine infectious anemia virus gag protein cytotoxic t lymphocyte epitopes.two defined cytotoxic t lymphocyte (ctl) epitopes from equine infectious anemia virus (eiav)-infected horses, equine leukocyte alloantigen (ela)-a5.1-restricted epitope 18a, and ela-a9-restricted epitope 28b-1 were evaluated for conservation among three wild-type eiav strains. epitope 18a variation occurred in all three wild-type eiav strains, while epitope 28b-1 varied in one strain. further, 12% amino acid changes occurred in the gag proteins of a recently isolated wild-type strain, documentin ...199910497109
endothelial cell infection in vivo by equine infectious anaemia virus.equine infectious anaemia virus (eiav) infection of horses is characterized clinically by recurrent episodes of fever, thrombocytopenia and anaemia. in vivo, the only site of virus replication that has been previously demonstrated for eiav is the tissue macrophage. in this study, in situ hybridization for eiav was combined with immunohistochemistry for cell-type-specific markers to identify infected endothelial cells. eiav-infected endothelial cells and macrophages were detected in horses infect ...199910501492
evaluation of antibody parameters as potential correlates of protection or enhancement by experimental vaccines to equine infectious anemia virus.we previously demonstrated in trials of a variety of experimental vaccines to equine infectious anemia virus (eiav) a remarkable spectrum of efficacy ranging from sterilizing protection to severe enhancement of virus replication and disease, depending on the immunization strategy used. this range of vaccine efficacy observed in vivo offers a unique opportunity for evaluating potential in vitro immune correlates of protection and enhancement. we describe here a comprehensive analysis and comparis ...199910502520
effects of long terminal repeat sequence variation on equine infectious anemia virus replication in vitro and in vivo.the long terminal repeat (ltr) is reported to be one of the most variable portions of the equine infectious anemia virus (eiav) genome. to date, however, no information is available on the effects of observed sequence variations on viral replication properties, despite a widespread assumption of the biological importance of eiav ltr variation. eiav ltr sequence variability is confined mostly to a small portion of the enhancer within the u3 segment of the ltr. analysis of published eiav ltr seque ...199910544113
evaluation of equine infectious anemia virus core proteins produced in a baculovirus expression system in agar gel immunodiffusion test and enzyme-linked immunosorbent assay.equine infectious anemia virus (eiav) core proteins (gag and p26) obtained from a baculovirus expression system were used in agar gel immunodiffusion (agid) and enzyme-linked immunosorbent assay (elisa) antigens to test seventy-six horse sera. those sera showed false-positive reaction in agid test using nisseiken antigen. however, none of them showed false-positive reaction with both of the expressed antigens. the 76 horse sera were also tested by elisa. the sera gave a high background in elisa ...19989879541
kinetic properties and stereospecificity of the monomeric dutpase from herpes simplex virus type 1.kinetic properties of the monomeric enzyme dutpase from herpes simplex virus type 1 (hsv) were investigated and compared to those previously determined for homotrimeric dutpases of bacterial and retroviral origins. the hsv and escherichia coli dutpases are equally potent as catalysts towards the native substrate dutp with a kcat/k(m) of about 10(7) m(-1) s(-1) and a k(m) of 0.3 microm. however, the viral enzymes are less specific than the bacterial enzyme. the hsv and e. coli dutpases show the s ...19989883909
disease induction by virus derived from molecular clones of equine infectious anemia virus.equine infectious anemia virus (eiav), a macrophage-tropic lentivirus, causes persistent infections of horses. a number of biologic features, including the rapid development of acute disease, the episodic nature of chronic disease, the propensity for viral genetic variation, and the ability for many infected animals to eventually control virus replication, render eiav a potentially useful model system for the testing of antiretroviral therapies and vaccine strategies. the utility of the eiav sys ...19989420249
development and characterization of an in vivo pathogenic molecular clone of equine infectious anemia infectious nonpathogenic molecular clone (19-2-6a) of equine infectious anemia virus (eiav) was modified by substitution of a 3.3-kbp fragment amplified by pcr techniques from a pathogenic variant (eiav(pv)) of the cell culture-adapted strain of eiav (eiav(pr)). this substitution consisted of coding sequences for 77 amino acids at the carboxyl terminus of the integrase, the s1 (encoding the second exon of tat), s2, and s3 (encoding the second exon of rev) open reading frames, the complete env ...19989445039
gene transfer vectors derived from equine infectious anemia virus.equine infectious anemia virus (eiav) is a lentivirus in the retrovirus family of viruses. replication-defective eiav vectors have been constructed that encode bacterial puromycin-n-acetyl transferase and e. coli beta-galactosidase. these vectors could be prepared with titers greater than 10(5) infectious units/ml and were able to act as vehicles to carry genes into cultured human cells. in addition, stable helper cell lines were created by modifying human 293 cells to express eiav proteins. unl ...19989930301
risk analysis of quarantine station performance: a case study of the importation of equine infectious anemia virus-infected horses into california.we examined the risk of importing and mistakenly releasing equine infectious anemia virus (eiav)-infected horses into california. a computer simulation model was constructed to evaluate current and alternative quarantine station procedures; 150,000 iterations were performed to simulate 15 different scenarios of 10,000 horses imported into the state over a 14-year period. simulation results showed that under current conditions of low eiav prevalence in exporting countries, increasing the quaranti ...19989526854
equine infectious anemia virus transactivator is a homeodomain-type protein.lentiviral transactivator (tat) proteins are essential for viral replication. tat proteins of human immunodeficiency virus type 1 and bovine immunodeficiency virus form complexes with their respective rna targets (tat responsive element, tar), and specific binding of the equine anemia virus (eiav) tat protein to a target tar rna is suggested by mutational analysis of the tar rna. structural data on equine infectious anemia virus tat protein reveal a helix-loop-helix-turn-helix limit structure ve ...19989545368
biological characterization of rev variation in equine infectious anemia virus.sequence analysis identified significant variation in the second exon of equine infectious anemia virus (eiav) rev. functional analysis indicated that limited amino acid variation in rev significantly altered the export activity of the protein but did not affect rev-dependent alternative splicing. eiav rev can mediate export through two independent cis-acting rev-responsive elements (rres), and differences among rev variants were more pronounced when both rres were present. variation in rev may ...19989557734
the aspartic proteinase from equine infectious anaemia virus. 19989561197
endotoxin treatment of equine infectious anaemia virus-infected horse macrophage cultures decreases production of infectious virus.lentiviruses replicate in cells of the immune system, and activation of immune cells has been shown to modulate virus replication. to determine the effects of macrophage activation on replication of equine infectious anaemia virus (eiav), primary horse macrophage cultures (hmcs) were established from 20 different horses, infected with an avirulent strain of eiav, and stimulated with 5 microg/ml of bacterial endotoxin. supernatants collected from hmcs were assayed for the presence of tumour necro ...19989568970
regulation of equine infectious anemia virus expression.equine infectious anemia virus (eiav) is an ungulate lentivirus that is related to human immunodeficiency virus (hiv). much of the understanding of lentiviral gene regulation comes from studies using hiv. hiv studies have provided insights into molecular regulation of eiav expression; however, much of the regulation of eiav expression stands in stark contrast to that of hiv. this review provides an overview of the current state of knowledge of eiav regulation by comparing and contrasting eiav ge ...19989570509
immunization with a recombinant envelope protein (rgp90) of eiav produces a spectrum of vaccine efficacy ranging from lack of clinical disease to severe enhancement.we have previously reported that immunization of ponies with a baculovirus-expressed recombinant surface unit envelope protein (rgp90) for equine infectious anemia virus (eiav) resulted in enhancement of disease symptoms and virus replication in 4 of 4 vaccine recipients subjected to a heterologous virus challenge (rpg90 i vaccine trial) (wang et al., 1994). to extend these studies of eiav vaccine enhancement, two additional and independent rgp90 vaccine trials (rgp90 ii and rgp90 iii) were perf ...19989614876
equine monocyte-derived macrophage cultures and their applications for infectivity and neutralization studies of equine infectious anemia virus.equine infectious anemia virus (eiav) has been shown to infect cells of monocyte/macrophage lineage. these primary cells are intrinsically difficult to obtain, to purify and to culture in vitro for extended periods of time. as a result, most in vitro studies concerning this lentivirus make use of primary equine fibroblasts or transformed canine or feline cell lines. we describe methods that yield reproducibly pure cultures of equine blood monocytes from peripheral blood mononuclear cells. the in ...19989628225
differential requirements for alternative splicing and nuclear export functions of equine infectious anemia virus rev protein.the rev protein of equine infectious anemia virus (erev) exports unspliced and partially spliced viral rnas from the nucleus. like several cellular proteins, erev regulates its own mrna by mediating an alternative splicing event. to determine the requirements for these functions, we have identified erev mutants that affect rna export or both export and alternative splicing. mutants were further characterized for subcellular localization, nuclear-cytoplasmic shuttling, and multimerization. none o ...19989632773
general method for the detection and in vitro expansion of equine cytolytic t lymphocytes.equine immunological research is hindered by the lack of a simple yet reliable general protocol by which to assay ctl activity specific for viral or parasitic antigens. we present here the first comprehensive analysis of the parameters necessary to reliably culture equine t cells and to analyze the antigen specific cytolytic activity of t lymphocytes utilizing the equine infectious anemia virus (eiav) infection of outbred ponies as a source for in vivo primed t lymphocytes. effective long-term i ...19989671126
equine infectious anemia virus is found in tissue macrophages during subclinical infection.the equine infectious anemia virus (eiav) often results in lifelong subclinical infection following early episodes of clinical disease. to identify the cellular reservoirs of eiav during subclinical infection, horses were infected with eiav and allowed to develop subclinical infections. horses with acute disease served as a basis for comparison. the tissue distribution, replication status, location of infected cells, and viral load were characterized by pcr for proviral dna and reverse transcrip ...19989696821
leptomycin b inhibits equine infectious anemia virus rev and feline immunodeficiency virus rev function but not the function of the hepatitis b virus posttranscriptional regulatory element.human immunodeficiency virus type 1 rev export depends upon the presence of the nuclear export signal (nes), a leucine-rich stretch of hydrophobic amino acids. recently, the nuclear nes-binding receptor has been identified as crm1 or exportin 1. rev export has been shown to be crm1 dependent. the function of the atypical nes-containing rev-like proteins of equine infectious anemia virus (eiav) and feline immunodeficiency virus (fiv) is inhibited by leptomycin b, a drug that specifically blocks n ...19989696859
hyperglobulinemia and lymphocyte subset changes in naturally infected, inapparent carriers of equine infectious anemia determine blood protein concentration, immunoglobulin concentration, and lymphocyte profiles in equine infectious anemia virus (eiav) seropositive, naturally infected horses without clinical signs of disease.19989706205
analysis of the polymerization kinetics of homodimeric eiav p51/51 reverse transcriptase implies the formation of a polymerase active site identical to heterodimeric eiav p66/51 reverse transcriptase.homodimeric eiav p51/51 and heterodimeric eiav p66/51 reverse transcriptase were purified in order to compare the different modes of dna synthesis supported by the enzymes. analysis of the dimerization behavior of the eiav enzymes indicates that the dimer stability of eiav reverse transcriptase enzymes is higher than that of their hiv-1 reverse transcriptase counterparts. eiav p51/51 polymerizes dna distributively whereas dna synthesis by eiav p66/51 is processive. steady-state and pre-steady-st ...19989724526
the s2 gene of equine infectious anemia virus is dispensable for viral replication in vitro.equine infectious anemia virus (eiav) contains the simplest genome among lentiviruses in that it encodes only three putative regulatory genes (s1, s2, s3) in addition to the canonical gag, pol, and env genes, presumably reflecting its limited tropism to cells of monocyte/macrophage lineage. tat and rev functions have been assigned to s1 and s3, respectively, but the specific function for the s2 gene has yet to be determined. thus, the function of s2 in virus replication in vitro was investigated ...19989733881
the tat protein of equine infectious anemia virus (eiav) activates cellular gene expression by read-through transcription.the tat protein of equine infectious anemia virus, eiav, was shown to augment viral gene expression, presumably through interaction with the tat responsive element, tar. recently, cell-free polyadenylation assays suggested that perturbation of the eiav tar secondary structure diminished polyadenylation efficiency. the present study indicates that the eiav tar regulates the efficiency of the 3'-end processing of viral rna also in transfected cells. moreover, our data suggest that the provision of ...19989756988
equine endothelial cells support productive infection of equine infectious anemia virus.previous cell infectivity studies have demonstrated that the lentivirus equine infectious anemia virus (eiav) infects tissue macrophages in vivo and in vitro. in addition, some strains of eiav replicate to high titer in vitro in equine fibroblasts and fibroblast cell lines. here we report a new cell type, macrovascular endothelial cells, that is infectible with eiav. we tested the ability of eiav to infect purified endothelial cells isolated from equine umbilical cords and renal arteries. infect ...19989765477
cdna excision in stable retroviral cdna transfectants is prevented by r removal.the present study provides evidence on the occurrence of dna rearrangement between the redundant 5' and 3' r domains of equine infectious anemia virus (eiav) tat cdna. this was correlated with a gradual loss of cdna copy number concomitantly with a decrease in gene expression. removal of the 5' ru5 abolished rearrangement and stabilized tat expression in eiav tat cdna transfectants. our data suggest that prior removal of the 5' r from cloned retroviral cdnas can impede dna rearrangement, thus pr ...19989784417
the role of oxygen in the antiviral activity of hypericin and hypocrellin.the light-induced antiviral activity of hypericin and hypocrellin in the presence and absence of oxygen was examined under experimental conditions where the effect of oxygen depletion could be quantified. there was a significant reduction of light-induced antiviral activity of hypericin and hypocrellin under hypoxic conditions. interestingly, antiviral activity of hypocrellin was not observed at low oxygen levels at which hypericin retained measurable virucidal activity. this suggests that addit ...19989796444
gag protein epitopes recognized by ela-a-restricted cytotoxic t lymphocytes from horses with long-term equine infectious anemia virus infection.most equine infectious anemia virus (eiav)-infected horses have acute clinical disease, but they eventually control the disease and become lifelong carriers. cytotoxic t lymphocytes (ctl) are considered an important immune component in the control of infections with lentiviruses including eiav, but definitive evidence for ctl in the control of disease in carrier horses is lacking. by using retroviral vector-transduced target cells expressing different gag proteins and overlapping synthetic pepti ...19989811694
equine infectious anemia virus gag polyprotein late domain specifically recruits cellular ap-2 adapter protein complexes during virion assembly.we have identified an interaction between the equine infectious anemia virus (eiav) late assembly domain and the cellular ap-2 clathrin-associated adapter protein complex. a yxxl motif within the eiav gag late assembly domain was previously characterized as a sequence critical for release of assembling virions. we now show that this yxxl sequence interacts in vitro with the ap-50 subunit of the ap-2 complex, while the functionally interchangeable late assembly domains carried by the rous sarcoma ...19989811764
maturation of immune responses to lentivirus infection: implications for aids vaccine development.the evaluation of attenuated vaccines in the simian immunodeficiency virus and equine infectious anemia virus animal models has demonstrated the ability of this immunization strategy to elicit broad and enduring immune protection from virus exposure. the development of protective immunity by these attenuated virus vaccines, however, has been shown to be time dependent and to be associated with a complex and lengthy maturation of immune responses over the first 6 to 8 months postinoculation. duri ...19989814952
toward a universal inhibitor of retroviral proteases: comparative analysis of the interactions of lp-130 complexed with proteases from hiv-1, fiv, and of the major problems encountered in antiviral therapy against aids is the emergence of viral variants that exhibit drug resistance. the sequences of proteases (prs) from related retroviruses sometimes include, at structurally equivalent positions, amino acids identical to those found in drug-resistant forms of hiv-1 pr. the statine-based inhibitor lp-130 was found to be a universal, nanomolar-range inhibitor against all tested retroviral prs. we solved the crystal structures of lp-130 in co ...19989827997
insertions, duplications and substitutions in restricted gp90 regions of equine infectious anaemia virus during febrile episodes in an experimentally infected horse.we have studied a horse which exhibited typical clinical signs of disease when experimentally infected with a non-adapted virulent strain of equine infectious anaemia virus (eiav), designated v70. five viruses (f1v, f2v, f3v, f4v and f5v) were recovered during periodic febrile episodes. cross-neutralization tests revealed that all of these variants and the parental v70 were antigenically distinct. sequencing of their full-length env gp90 genes and gp45 5' sequences revealed novel mutations at a ...19979129653
control of equine infectious anemia virus is not dependent on adcc mediating antibodies.horses infected with equine infectious anemia virus (eiav) have recurrent episodes of viremia which are eventually controlled, but the immune mechanisms have not been identified. antibodies were detected to the surface of eiav-infected cells within 1 month postinfection and remained for at least 3.5 years postinfection. these antibodies recognized cell surface-exposed envelope (env) glycoproteins, but could not mediate antibody dependent cellular cytotoxicity (adcc) using eiav-wsu5-infected equi ...19979143283
cloning, expression, purification, and characterization of the major core protein (p26) from equine infectious anemia virus.the gene coding for the major core protein (p26) of the lentivirus equine infectious anemia virus (eiav) was cloned from eiav infected serum, expressed in e. coli, and the resultant protein purified to electrophoretic homogeneity. the protein was expressed in a soluble form and was purified by conventional protein separation methods. when analyzed by sds-page, under both reducing and non-reducing conditions, the purified protein migrated as a 26 kda monomer. recombinant p26 (rp26), therefore, do ...19979165100
characterization and mutational studies of equine infectious anemia virus dutpase.the macrophage tropic lentivirus, equine infectious anemia virus (eiav), encodes a dutpase in the pol gene that is required for efficient replication in macrophages. two naturally occurring variants of the enzyme were expressed as recombinant proteins in escherichia coli; metal chelate affinity chromatography was used to purify histidine-tagged recombinant enzymes to greater than 80% homogeneity in a single chromatographic step. biochemical and enzymatic analyses of these preparations suggest th ...19979187238
localized sequence heterogeneity in the long terminal repeats of in vivo isolates of equine infectious anemia virus.the role of in vivo long terminal repeat (ltr) sequence variation of the lentivirus equine infectious anemia virus (eiav) has not been explored. in this study, we investigated the heterogeneity found in the ltr sequences from seven eiav-seropositive horses: three horses with clinical disease and four horses without any detectable signs of disease. ltr sequences were targeted in this study because the ltr u3 enhancer region of tissue culture-derived isolates has been identified as one of the few ...19979188555
in vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.equine infectious anemia virus (eiav) is a good model for studying mechanisms generating escaped retrovirus variants. we previously sequenced the entire gp90-encoding region of 22 cdna clones obtained from five antigenically distinct isolates (f1v to f5v) recovered during febrile episodes in horse 493 experimentally infected with the japanese virulent eiav strain v70. the results showed that the mutations occurred in the principal neutralizing domain (pnd) by insertions/duplications. in this stu ...19979188568
mutations in hiv reverse transcriptase which alter rnase h activity and decrease strand transfer efficiency are suppressed by hiv nucleocapsid protein.structural studies of authentic hiv reverse transcriptase (rt) suggest a role for the p51 carboxyl terminus in forming an active rnase h conformation [rodgers, d. w., gamblin, s. j., harris, b. a., ray, s., culp, j. s., hellmig, b., woolf, d. j., debouck, c. & harrison, s. c. (1995) proc. natl. acad. sci. usa 92, 1222-1226]. we have purified mutant rt heterodimers containing deletion of 5, 9, or 13 amino acids from the p51 carboxyl terminus. these "selectively deleted" heterodimers have been ana ...19979192628
tumor necrosis factor-alpha production and disease severity after immunization with enriched major core protein (p26) and/or infection with equine infectious anemia virus.cardinal features of equine infectious anemia (eia) include fever, hemolytic anemia and thrombocytopenia during the acute phase of the disease, and cachexia and anemia seen during the chronic phase. these signs are thought to result from the release of inflammatory cytokines such as tnf-alpha. in order to determine if tnf-alpha has a role in the pathogenesis of acute eia and vaccine-induced disease enhancement, we measured plasma concentrations of tnf-alpha in ponies immunized with virus enriche ...19979239836
equine infectious anemia virus utilizes a yxxl motif within the late assembly domain of the gag p9 protein.we have previously demonstrated that the gag p9 protein of equine infectious anemia virus (eiav) is functionally homologous with rous sarcoma virus (rsv) p2b and human immunodeficiency virus type 1 (hiv-1) p6 in providing a critical late assembly function in rsv gag-mediated budding from transfected cos-1 cells (l. j. parent et al., j. virol. 69:5455-5460, 1995). in light of the absence of amino acid sequence homology between eiav p9 and the functional homologs of rsv and hiv-1, we have now desi ...19979261374
scientists to pursue aids vaccine based on eia model. 19979262653
suppression of megakaryocyte colony growth by plasma from foals infected with equine infectious anemia virus.foals infected with equine infectious anemia virus become thrombocytopenic 7 to 20 days after virus inoculation, and within a few days following the onset of detectable viremia. the thrombocytopenia is associated with suppression of platelet production. possible mediators of suppression of thrombopoiesis include tumor necrosis factor-alpha (tnf-alpha) and transforming growth factor-beta (tgf-beta), cytokines that are released during inflammation. to assess effects of plasma or serum from infecte ...19979310486
dutpase from the retrovirus equine infectious anemia virus: specificity, turnover and inhibition.the kinetic properties of dutpase from equine infectious anemia virus (eiav) were investigated. k(m) (1.1 +/- 0.1 microm) and k(cat) (25 s(-1)) were found to be independent of ph in the neutral ph range. above ph 8.0, k(m) increases slightly. below ph 6.0, the enzyme is rapidly deactivated. detergent was found to enhance activity, leaving k(m) and k(cat) unaffected. compared to the escherichia coli dutpase, the eiav enzyme is equally potent in hydrolyzing dutp, but less specific. inhibition of t ...19979315700
flow cytometric method for detecting thiazole orange-positive (reticulated) platelets in thrombocytopenic evaluate a method for detecting thiazole orange-positive (to+, reticulated) platelets in equine blood, using flow cytometry.19979328660
elevation of cytokines associated with the thrombocytopenia of equine infectious anaemia.thrombocytopenia is a common finding in infection with equine infectious anaemia virus (eiav), a lentivirus with some homology to human immunodeficiency virus (hiv). the thrombocytopenia of eia, like that in some hiv patients, appears to have a multifactorial pathogenesis. to investigate the decreased platelet production seen in experimental eia, the levels of three potential negative regulators of platelet production--tumour necrosis factor-alpha (tnf-alpha), transforming growth factor-beta (tg ...19979349475
north american and french caprine arthritis-encephalitis viruses emerge from ovine maedi-visna viruses.the full extent of genetic diversity among small ruminant lentiviruses (srlvs), i.e., caprine arthritis encephalitis viruses (caevs) and maedi-visna viruses (mvvs), remains unknown. this is due in part to the fact that few sequences of caev are available. to contribute to this knowledge, gag, pol, and env nucleotide sequences from an srlv named ca680 originating from a goat from western france were determined. this analysis revealed that this virus is closely related to the cork and 63 caev amer ...19979356342
novel antimicrobial peptides derived from human immunodeficiency virus type 1 and other lentivirus transmembrane proteins.we have previously described a conserved set of peptides derived from lentiviral envelope transmembrane proteins that are similar to the natural antimicrobial peptides cecropins and magainins in overall structure but bear no sequence homology to them or other members of their class. we describe here an evaluation of the antimicrobial properties of these virally derived peptides, designated lentivirus lytic peptides (llps). the results of this study demonstrate that they are potent and selective ...19979371339
novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.we have investigated the genetic evolution of three functionally distinct regions of the equine infectious anemia virus (eiav) genome (env, rev, and long terminal repeat) during recurring febrile episodes in a pony experimentally infected with a well-characterized reference biological clone designated eiav(pv). viral populations present in the plasma of an eiav(pv)-infected pony during sequential febrile episodes (18, 34, 80, 106, and 337 days postinfection) were amplified from viral rna, analyz ...19979371627
frequency of memory cytotoxic t lymphocytes to equine infectious anemia virus proteins in blood from carrier horses.horses with equine infectious anemia virus (eiav) have episodes of viremia and disease; however, most eventually become inapparent carriers. a possible mechanism of control is cytotoxic t lymphocytes (ctl). to evaluate ctl in inapparent carriers with low viral loads, peripheral blood mononuclear cells (pbmc) were stimulated in vitro with autologous eiav-infected pbmc and human il-2 to detect memory ctl (ctlm). in initial studies, three carriers had ctlm and one of these had low-level effector ct ...19979375012
infection of bone marrow macrophages by equine infectious anemia characterize infection of bone marrow-derived macrophages (bmdm) with equine infectious anemia virus (eiav) by determining virus production, effects on viability, and induction of cytokines.19979401688
maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process.equine infectious anemia virus (eiav) provides a natural model system by which immunological control of lentivirus infections may be studied. to date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by eiav has been conducted. therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of eiav infection. u ...19979094660
genetic variation of envelope gp90 gene of equine infectious anemia virus isolated from an experimentally infected horse.six strains of equine infectious anemia virus (eiav) were recovered from febrile and non-febrile stages of a horse experimentally infected with the p337-v70 strain given once to a horse. the env gp90 genes of the isolates, the p337-v70 and p337-v26, avirulent virus derived from the p337-v70 strain, were sequenced. a comparison of the gp90 gene sequences revealed that amino acid variations among the viruses tested showed as high as 8.2 to 11.5%. in addition, the comparison also indicated that the ...19979450237
application of equine infectious anemia virus core proteins produced in a baculovirus expression system to serological diagnosis.equine infectious anemia virus (eiav) core proteins were obtained from a baculovirus expression system. recombinant baculoviruses (rbvs) highly expressed the gag precursor and p26 antigens in an rbv-infected sf21 cell culture supernatant. enzyme-linked immunosorbent assay (elisa) and agar gel immunodiffusion (agid) were conducted using the expressed proteins to detect antibodies from experimentally infected horses. the expressed antigens showed low background levels, high specificity and sensiti ...19979492183
specificity of retroviral proteinases based on substrates containing tyrosine and proline at the site of cleavage.the retroviral proteinase (pr) plays crucial roles in the viral life cycle, therefore it is a target for chemotherapy. however, resistance rapidly develops due to frequent mutations. studies to determine the common features of the specificity of different retroviral prs may help to design broad spectrum inhibitors and reduce the possibility of viable mutants. we have studied the specificity of various retroviral proteinases including those the pr of hiv-1, hiv-2, equine infectious anemia virus a ...199711173643
hiv and human endogenous retroviruses: an hypothesis with therapeutic implications.the enzyme dutp pyrophosphatase (dutpase, ec is essential for cellular dna replication and cell viability by virtue of its role in reducing the availability of dutp as a substrate for dna polymerases. several members of the onco- and lentivirus families of retroviruses encode dutpases and mutant strains of these viruses defective in this enzyme exhibit suboptimal replication kinetics. among the lentiviruses there exists a surprising phylogenetic discontinuity in the distribution of dut ...19969104494
equine infectious anemia virus replication is upregulated during differentiation of blood monocytes from acutely infected horses.equine infectious anemia virus is a lentivirus that replicates in mature tissue macrophages of horses. ponies were infected with equine infectious anemia virus. during febrile episodes, proviral dna was detectable, but viral mrna was not detectable. as cultured blood monocytes from these ponies differentiated into macrophages, viral expression was upregulated. in situ hybridization confirmed that viral transcription occurred in mature macrophages.19968523576
fine specificity of equine infectious anaemia virus gp90-specific antibodies associated with protective and enhancing immune responses in experimentally infected and immunized ponies.equine infectious anaemia virus (eiav) provides a model for examining the natural immunological control of a persistent lentivirus infection and for evaluating the efficacy of various vaccine strategies. as an initial characterization of antibody responses associated with protective or enhancing immune responses elicited by experimental infections or vaccinations, we have utilized synthetic peptide elisa to characterize the fine specificity of antibodies to linear determinants of the eiav surfac ...19968601778
specific derivatization of the active site tyrosine in dutpase perturbs ligand binding to the active site.selective modification of one (of three) tyrosine residue per enzyme monomer leads to inactivation of dutpase of the retrovirus equine infectious anemia virus (eiav). the substrate dump and the cofactor mg2+ protect against inactivation and modification, in agreement with the study on e. coli dutpase (vertessy et al. (1994) biochim. biophys. acta 1205, 146-150). amino acid analyses of nitrated dutpases confirmed tyr-selectivity of modification. the nitrated residue in e. coli dutpase was identif ...19968604980
isolation of an 11-kda protein associated with the topoisomerase i activity from equine infectious anemia virus.we have previously demonstrated the presence of topoisomerase i (topo i) activity in purified retroviral particles (i.e., human immunodeficiency virus type 1, equine infectious anemia virus-eiav and moloney murine leukemia virus). in our present work, an attempt was made to determine the nature and origin of the protein that is associated with this activity. for that purpose we have isolated the topo i activity from equine infectious anemia virus cores and showed that a major protein band of an ...19968607786
a common mechanism for the enhancement of mrna 3' processing by u3 sequences in two distantly related lentiviruses.the protein coding regions of all retroviral pre-mrnas are flanked by a direct repeat of r-u5 sequences. in many retroviruses, the r-u5 repeat contains a complete core poly(a) site-composed of a highly conserved aauaaa hexamer and a gu-rich downstream element. a mechanism that allows for the bypass of the 5' core poly(a) site and the exclusive use of the 3' core poly(a) site must therefore exist. in human immunodeficiency virus type 1 (hiv-1), sequences within the u3 region appear to play a key ...19968627681
interactions among sr proteins, an exonic splicing enhancer, and a lentivirus rev protein regulate alternative splicing.we examine here the roles of cellular splicing factors and virus regulatory proteins in coordinately regulating alternative splicing of the tat/rev mrna of equine infectious anemia virus (eiav). this bicistronic mrna contains four exons; exons 1 and 2 encode tat, and exons 3 and 4 encode rev. in the absence of rev expression, the four-exon mrna is synthesized exclusively, but when rev is expressed, exon 3 is skipped to produce an mrna that contains only exons 1, 2, and 4. we identify a purine-ri ...19968628299
comparative studies on the substrate specificity of avian myeloblastosis virus proteinase and lentiviral proteinases.the retroviral proteinase (pr) seems to play crucial roles in the viral life cycle, therefore it is an attractive target for chemotherapy. previously we studied the specificity of human immunodeficiency virus (hiv) type 1 and type 2 as well as equine infectious anemia virus prs using oligopeptide substrates. here a similar approach is used to characterize the specificity of avian myeloblastosis virus (amv) pr and to compare it with those of the previously characterized lentiviral prs. all peptid ...19968636100
nuclear transport of human immunodeficiency virus type 1, visna virus, and equine infectious anemia virus rev proteins: identification of a family of transferable nuclear export signals.the human immunodeficiency virus type 1 rev trans activator binds directly to unspliced viral mrna in the nucleus and activates its transport to the cytoplasm. in additon to the sequences that confer rna binding and nuclear localization, rev has a carboxy-terminal region, the activation domain, whose integrity is essential for biological activity. because it has been established that rev constitutively exits and reenters the nucleus and that the activation domain is required for nuclear exit, it ...19968642662
involvement of c-terminal structural elements of equine infectious anemia virus reverse transcriptase in dna polymerase and ribonuclease h order to investigate the modes of dna synthesis supported by the 66 and 51 kda subunits of equine infectious anemia virus reverse transcriptase (eiav rt), recombinant p66 polypeptides containing a modified ribonuclease h (rnase h) domain were purified and evaluated. defined heteropolymeric template-primer combinations and high-resolution gel electrophoresis provided a qualitative evaluation of dna polymerase and rnase h activities, while dnase i footprinting revealed features of replication c ...19968648620
genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus.equine infectious anemia virus (eiav) provides a uniquely dynamic system in which to study the mechanism and role of genomic variation in lentiviral persistence and pathogenesis. we have used a shetland pony model of infection to investigate the association of specific long terminal repeat (ltr) and env gene genomic sequences with the initiation of infection and the onset of disease. we analyzed viral rna isolated from a pathogenic stock of virus (eiav pv) and from plasma taken during the first ...19968648664
inhibitory activity of the equine infectious anemia virus major 5' splice site in the absence of rev.the major 5' splice site of equine infectious anemia virus (eiav) conforms to the consensus 5' splice site in eight consecutive positions and is located immediately upstream of the gag aug. our results show that the presence of this 5' splice site on the eiav gag mrna decreases gag production 30- to 60-fold. this is caused by inefficient nuclear mrna export and inefficient mrna utilization. inhibition could be overcome by providing human immunodeficiency virus type 1 rev/rev-responsive element, ...19968648699
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