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unclosed hiv-1 capsids suggest a curled sheet model of assembly.the rna genome of retroviruses is encased within a protein capsid. to gather insight into the assembly and function of this capsid, we used electron cryotomography to image human immunodeficiency virus (hiv) and equine infectious anemia virus (eiav) particles. while the majority of viral cores appeared closed, a variety of unclosed structures including rolled sheets, extra flaps, and cores with holes in the tip were also seen. simulations of nonequilibrium growth of elastic sheets recapitulated ...201323079241
the maturational refolding of the β-hairpin motif of equine infectious anemia virus capsid protein extends its helix α1 at capsid assembly locus.a retroviral capsid (ca) protein consists of two helical domains, ca(n) and ca(c), which drive hexamer and dimer formations, respectively, to form a capsid lattice. the n-terminal 13 residues of ca refold to a β-hairpin motif upon processing from its precursor polyprotein gag. the β-hairpin is essential for correct ca assembly but unexpectedly it is not within any ca oligomeric interfaces. to understand the β-hairpin function we studied the full-length ca protein from equine infectious anemia vi ...201323184932
genetic characterization by composite sequence analysis of a new pathogenic field strain of equine infectious anemia virus from the 2006 outbreak in ireland.equine infectious anemia virus (eiav), the causative agent of equine infectious anaemia (eia), possesses the least-complex genomic organization of any known extant lentivirus. despite this relative genetic simplicity, all of the complete genomic sequences published to date are derived from just two viruses, namely the north american eiav(wyoming) (eiav(wy)) and chinese eiav(liaoning) (eiav(lia)) strains. in 2006, an outbreak of eia occurred in ireland, apparently as a result of the importation o ...201323175240
sero-surveillance of equine infectious anemia virus in equines in india during more than a decade (1999-2012).equine infectious anemia (eia) is a retroviral infection of horses. horses infected by eia virus (eiav) become inapparent carriers that remain asymptomatic for the remainder of their life span and serve as infection source to other horses. in this study, agar gel immunodiffusion test and elisa were used to investigate the presence of antibodies to eiav in equines. a total of 67,042 equine serum samples from 19 states and two union territories were tested during april 1999 to september 2012. the ...201324426302
development, evaluation, and laboratory validation of immunoassays for the diagnosis of equine infectious anemia (eia) using recombinant protein produced from a synthetic p26 gene of eia virus.equine infectious anemia (eia)-a retroviral disease caused by equine infectious anemia virus (eiav)-is a chronic, debilitating disease of horses, mules, and donkeys. eiav infection has been reported worldwide and is recognized as pathogen of significant economic importance to the horse industry. this disease falls under regulatory control program in many countries including india. control of eia is based on identification of inapparent carriers by detection of antibodies to eiav in serologic tes ...201324426297
comprehensive analysis of the overall codon usage patterns in equine infectious anemia virus.equine infectious anemia virus (eiav) is an important animal model for understanding the relationship between viral persistence and the host immune response during lentiviral infections. comparison and analysis of the codon usage model between eiav and its hosts is important for the comprehension of viral evolution. in our study, the codon usage pattern of eiav was analyzed from the available 29 full-length eiav genomes through multivariate statistical methods.201324359511
contribution of sam and hd domains to retroviral restriction mediated by human samhd1.the human samhd1 protein is a novel retroviral restriction factor expressed in myeloid cells. previous work has correlated the deoxynucleotide triphosphohydrolase activity of samhd1 with its ability to block hiv-1 and siv(mac) infection. samhd1 is comprised of the sterile alpha motif (sam) and histidine-aspartic (hd) domains; however the contribution of these domains to retroviral restriction is not understood. mutagenesis and deletion studies revealed that expression of the sole hd domain of sa ...201323158101
inhibition of virus replication and induction of human tetherin gene expression by equine ifn-α1.type i interferons (ifns) play important roles in the defense of host cells against viral infection by inducing the expression of a diverse range of antiviral factors. ifns from different animals likely share similar features with human ifns, and some of them have cross-species activities. equine ifn-α was proved effective in both equine and human cells. however, the previous studies mostly focused on the inhibition of virus induced cytopathic effects. in this study, we used virus-specific assay ...201324144682
lessons in aids vaccine development learned from studies of equine infectious, anemia virus infection and immunity.equine infectious anemia (eia), identified in 1843 [1] as an infectious disease of horses and as a viral infection in 1904, remains a concern in veterinary medicine today. equine infectious anemia virus (eiav) has served as an animal model of hiv-1/aids research since the original identification of hiv. similar to other lentiviruses, eiav has a high propensity for genomic sequence and antigenic variation, principally in its envelope (env) proteins. however, eiav possesses a unique and dynamic di ...201324316675
interstitial lung disease associated with equine infectious anemia virus infection in horses.eia (equine infectious anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. other routes of transmission have been poorly explored. we evaluated the potential of eiav (equine infectious anemia virus) to induce pulmonary lesions in naturally infected equids. lungs from 77 eiav seropositive horses have been collected in romania and france. three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflam ...201324289102
the soluble form of the eiav receptor encoded by an alternative splicing variant inhibits eiav infection of target cells.equine lentivirus receptor 1 (elr1) has been identified as the sole receptor for equine infectious anemia virus (eiav) and is a member of the tumor necrosis factor receptor (tnfr) superfamily. in addition to the previously described membrane-associated form of elr1, two other major alternative splicing variant mrnas were identified in equine monocyte-derived macrophages (emdms). one major spliced species (elr1-in) contained an insertion of 153 nt, which resulted in a premature stop codon situate ...201324278125
equine infectious anemia and equine infectious anemia virus in 2013: a review.a detailed description of equine infectious anemia virus and host responses to it are presented. current control and eradication of the infection are discussed with suggestions for improvements to increase their effectiveness.201324183747
nucleoporin nup153 phenylalanine-glycine motifs engage a common binding pocket within the hiv-1 capsid protein to mediate lentiviral infectivity.lentiviruses can infect non-dividing cells, and various cellular transport proteins provide crucial functions for lentiviral nuclear entry and integration. we previously showed that the viral capsid (ca) protein mediated the dependency on cellular nucleoporin (nup) 153 during hiv-1 infection, and now demonstrate a direct interaction between the ca n-terminal domain and the phenylalanine-glycine (fg)-repeat enriched nup153 c-terminal domain (nup153(c)). nup153(c) fused to the effector domains of ...201324130490
escrt requirements for eiav budding.retroviruses and many other enveloped viruses usurp the cellular escrt pathway to bud from cells. however, the stepwise process of escrt-mediated virus budding can be challenging to analyze in retroviruses like hiv-1 that recruit multiple different escrt factors to initiate budding.201324107264
determining interdomain structure and dynamics of a retroviral capsid protein in the presence of oligomerization: implication for structural transition in capsid assembly.capsid (ca) proteins from all retroviruses, including hiv-1, are structurally homologous dual-domain helical proteins. they form a capsid lattice composed of unitary symmetric ca hexamers. x-ray crystallography has shown that within each hexamer a monomeric ca adopts a single conformation, where most helices are parallel to the symmetry axis. in solution, large differences in averaged nmr spin relaxation rates for the two domains were observed, suggesting they are dynamically independent. one re ...201323906107
envelope determinants of equine lentiviral vaccine protection.lentiviral envelope (env) antigenic variation and associated immune evasion present major obstacles to vaccine development. the concept that env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with env variation have yet to be determined. we reported an attenuated equine infectious anemia virus (eiav) vaccine study that directly examined the effect of lentiviral env sequence variation on vaccine efficacy. the study identified a ...201323785473
reverse mutation of the virulence-associated s2 gene does not cause an attenuated equine infectious anemia virus strain to revert to pathogenicity.the contribution of s2 accessory gene of equine infectious anemia virus (eiav) to the virulence of pathogenic strains was investigated in the present study by reverse mutation of all four consensus s2 mutation sites in an attenuated eiav proviral strain, fddv3-8, to the corresponding sequences of a highly pathogenic strain dv117. the s2 reverse-mutated recombinant strain fddvs2r1-2-3-4 replicated with similar kinetics to fddv3-8 in cultivated target cells. in contrast to the results of other stu ...201323763769
virus-specific effects of trim5α(rh) ring domain functions on restriction of retroviruses.the tripartite motif protein trim5α restricts particular retrovirus infections by binding to the incoming capsid and inhibiting the early stage of virus infection. the trim5α ring domain exhibits e3 ubiquitin ligase activity and assists the higher-order association of trim5α dimers, which promotes capsid binding. we characterized a panel of ring domain mutants of the rhesus monkey trim5α (trim5α(rh)) protein. the ring domain function that significantly contributed to retroviral restriction depen ...201323637418
transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: safety and biodistribution of stargen for stargardt disease.stargen is an equine infectious anemia virus (eiav)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (atp)-binding cassette transporter (abca4) protein that is mutated in stargardt disease (stgd1), a juvenile macular dystrophy. eiav vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. the safety and biodistribution of stargen fol ...201323620430
production of equine infectious anemia virus (eiav) antigen in pichia pastoris.equine infectious anemia (eia) is a persistent lentivirus infection of horses which causes a chronic clinical condition with worldwide importance in veterinary medicine. the p26 protein is usually prepared for use as an antigen in serological tests for eia diagnosis since it is a well-conserved gene sequence and very immunogenic. in view of the ability of yeast to make post-translational modifications of proteins, this study was carried out to allow pichia pastoris to be used for the expression ...201323603438
prevalence and risk factors for equine infectious anemia in poconé municipality, northern brazilian pantanal.serum samples collected from 547 equids in the pantanal region of brazil were evaluated for antibodies to equine infectious anemia virus (eiav) by the agar gel immunodiffusion test. risk factors associated with eiav seropositivity were evaluated and spatial dependence investigated using a spatial lag model. eiav prevalence on farms in the pantanal was 52.0% (13/25) with adjusted prevalence between equids of 31.5% (17.4-48.8% 95% ci). intra-herd prevalence ranged from 5.0 to 77.0%. statistical an ...201323517766
high efficiency gene transfer to airways of mice using influenza hemagglutinin pseudotyped lentiviral vectors.a limitation to efficient lentivirus-mediated airway gene transfer is the lack of receptors to commonly used viral envelopes on the luminal surface of airway epithelia. the use of viral envelopes with natural tropism to the airway could be useful for overcoming this limitation.201323319179
amplification of complete gag gene sequences from geographically distinct equine infectious anemia virus isolates.in the current study, primers described previously and modified versions of these primers were evaluated for amplification of full-length gag genes from different equine infectious anemia virus (eiav) strains from several countries, including the usa, germany and japan. each strain was inoculated into a primary horse leukocyte culture, and the full-length gag gene was amplified by reverse transcription polymerase chain reaction. each amplified gag gene was cloned into a plasmid vector for sequen ...201323318370
understanding virus-host dynamics following eiav infection in scid horses.we develop a mathematical model for the interaction between two competing equine infectious anemia virus strains and neutralizing antibodies. we predict that elimination of one or both virus strains depends on the initial antibody levels, the strength of antibody mediated neutralization, and the persistence of antibody over time. we further show that the ability of a subdominant, neutralization resistant virus to dominate the infection transiently or permanently is dependent on the antibody-medi ...201424252283
equine tetherin blocks retrovirus release and its activity is antagonized by equine infectious anemia virus envelope protein.human tetherin is a host restriction factor that inhibits replication of enveloped viruses by blocking viral release. tetherin has an unusual topology that includes an n-terminal cytoplasmic tail, a single transmembrane domain, an extracellular domain, and a c-terminal glycosylphosphatidylinositol anchor. tetherin is not well conserved across species, so it inhibits viral replication in a species-specific manner. thus, studies of tetherin activities from different species provide an important to ...201424227834
use of heavy water (d2o) in developing thermostable recombinant p26 protein based enzyme-linked immunosorbent assay for serodiagnosis of equine infectious anemia virus infection.thermostabilizing effect of heavy water (d2o) or deuterium oxide has been demonstrated previously on several enzymes and vaccines like oral poliovirus vaccine and influenza virus vaccine. in view of the above observations, effect of heavy water on in situ thermostabilization of recombinant p26 protein on enzyme-linked immunosorbent assay (elisa) for serodiagnosis of equine infectious anemia virus (eiav) infection was investigated in the present study. the carbonate-bicarbonate coating buffer was ...201424523642
computational modeling suggests dimerization of equine infectious anemia virus rev is required for rna binding.the lentiviral rev protein mediates nuclear export of intron-containing viral rnas that encode structural proteins or serve as the viral genome. following translation, hiv-1 rev localizes to the nucleus and binds its cognate sequence, termed the rev-responsive element (rre), in incompletely spliced viral rna. rev subsequently multimerizes along the viral rna and associates with the cellular crm1 export machinery to translocate the rna-protein complex to the cytoplasm. equine infectious anemia vi ...201425533001
a unique evolution of the s2 gene of equine infectious anemia virus in hosts correlated with particular infection statuses.equine infectious anemia virus (eiav) is a member of the lentivirus genus in the retroviridae family that exhibits a genomic structure similar to that of hiv-1. the s2 accessory proteins play important roles in viral replication in vivo and in viral pathogenicity; however, studies on s2 evolution in vivo are limited. this study analyzed the evolutionary characteristics of the s2 gene of a pathogenic eiav strain, eiavln40, in four experimentally infected horses. the results demonstrated that 14.7 ...201425390683
equine infectious anemia virus in japan: viral isolates v70 and v26 are of north american not japanese origin. 201425265930
development of antigen capture elisa for the quantification of eiav p26 protein.an antigen capture enzyme-linked immunosorbent assay (ac-elisa) was established based on two monoclonal antibodies (mabs) for the quantification of equine infectious anemia virus (eiav). two p26-specific monoclonal antibodies were developed in mice. the mab 9h8 was coated in microtiter plates as the capture antibody; the other mab, 1g11, was coupled to horseradish peroxidase (hrp) and used as the detection antibody. the limit of detection for the eiav p26 protein was 0.98 ng/ml, and the linearit ...201425256618
antiviral potency and functional analysis of tetherin orthologues encoded by horse and donkey.tetherin is an interferon-inducible host cell factor that blocks the viral particle release of the enveloped viruses. most knowledge regarding the interaction between tetherin and viruses has been obtained using the primate lentiviral system. however, much less is known about the functional roles of tetherin on other lentiviruses. equine infectious anemia virus (eiav) is an important macrophage-tropic lentivirus that has been widely used as a practical model for investigating the evolution of th ...201425158826
comparative analysis of ltr and structural genes in an equine infectious anemia virus strain isolated from a feral horse in japan.although equine infectious anemia virus (eiav) poses a major threat to the equine industry worldwide, the molecular epidemiology of this virus is poorly understood. recently, an eiav strain (eiavmiyazaki2011-a) representing a new monophyletic group was discovered in feral horses in southern japan. in the present study, the eiavmiyazaki2011-a proviral genome is compared with evolutionarily divergent eiav isolates to investigate conservation of functional elements or motifs within the long termina ...201425149072
infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (eiav) strain induces a strong resistance to the infection by a virulent eiav strain.the chinese attenuated equine infectious anemia virus (eiav) vaccine has successfully protected millions of equine animals from eia disease in china. given that the induction of immune protection results from the interactions between viruses and hosts, a better understanding of the characteristics of vaccine strain infection and host responses would be useful for elucidating the mechanism of the induction of immune protection by the chinese attenuated eiav strain. in this study, we demonstrate i ...201425106750
effects of human samhd1 polymorphisms on hiv-1 susceptibility.samhd1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting cd4+ t cells by hiv-1. here we explored the antiviral activity and biochemical properties of human samhd1 polymorphisms. our studies focused on human samhd1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. the different human samhd1 polymorphisms were tested for their ability to block hiv-1 ...201425010268
structural and biochemical insights into the v/i505t mutation found in the eiav gp45 vaccine strain.the equine infectious anemia virus (eiav) is a lentivirus of the retrovirus family, which causes persistent infection in horses often characterized by recurrent episodes of high fever. it has a similar morphology and life cycle to the human immunodeficiency virus (hiv). its transmembrane glycoprotein, gp45 (analogous to gp41 in hiv), mediates membrane fusion during the infection. however, the post-fusion conformation of eiav gp45 has not yet been determined. eiav is the first member of the lenti ...201424656154
evolution of the retroviral restriction gene fv1: inhibition of non-mlv retroviruses.fv1 is the prototypic restriction factor that protects against infection by the murine leukemia virus (mlv). it was first identified in cells that were derived from laboratory mice and was found to be homologous to the gag gene of an endogenous retrovirus (erv). to understand the evolution of the host restriction gene from its retroviral origins, fv1s from wild mice were isolated and characterized. most of these possess intact open reading frames but not all restricted n-, b-, nr-or nb-tropic ml ...201424603659
optical control of retrogradely infected neurons using drug-regulated "tloop" lentiviral vectors.many approaches that use viral vectors to deliver transgenes have limited transduction efficiency yet require high levels of transgene expression. in particular, infection via axon terminals is relatively inefficient but is a powerful means of achieving infection of specific neuron types. combining this with optogenetic approaches requires high gene expression levels that are not typically achieved with nontoxic retrogradely infecting vectors. we generated rabies glycoprotein-pseudotyped lentivi ...201424572099
suppression of neovascularization of donor corneas by transduction with equine infectious anemia virus-based lentiviral vectors expressing endostatin and angiostatin.corneal transplantation is the oldest and one of the most successful transplant procedures with a success rate in many studies in excess of 90%. the high success rate is mainly attributable to the relatively immune-privileged status of the eye and the fact that the cornea is largely avascular. however, the success rate in patients with failed grafts is much lower such that regrafting is frequently the top indication for corneal transplantation in many centers. neovascularization is the most impo ...201424460027
core-binding factor subunit beta is not required for non-primate lentiviral vif-mediated apobec3 degradation.viral infectivity factor (vif) is required for lentivirus fitness and pathogenicity, except in equine infectious anemia virus (eiav). vif enhances viral infectivity by a cullin5-elongin b/c e3 complex to inactivate the host restriction factor apobec3. core-binding factor subunit beta (cbf-β) is a cell factor that was recently shown to be important for the primate lentiviral vif function. non-primate lentiviral vif also degrades apobec3 through the proteasome pathway. however, it is unclear wheth ...201425122780
the dutpase-related gene of bovine immunodeficiency virus is critical for viral replication, despite the lack of dutpase activity of the encoded protein.deoxyuridine 5'-triphosphate nucleotide-hydrolases (dutpases) are essential for maintaining low intra-cellular dutp/dttp ratios. therefore, many viruses encode this enzyme to prevent dutp incorporation into their genomes instead of dttp. among the lentiviruses, the non-primate viruses express dutpases. in bovine immunodeficiency virus (biv), the putative dutpase protein is only 74 residues-long, compared to ~130 residues in other lentiviruses.201425117862
role of cullin-elonginb-elonginc e3 complex in bovine immunodeficiency virus and maedi-visna virus vif-mediated degradation of host a3z2-z3 proteins.all lentiviruses except equine infectious anemia virus (eiva) antagonize antiviral family apobec3 (a3) proteins of the host through viral vif proteins. the mechanism by which vif of human, simian or feline immunodeficiency viruses (hiv/siv/fiv) suppresses the corresponding host a3s has been studied extensively.201425213124
tabanids: neglected subjects of research, but important vectors of disease agents!tabanids are nuisance pests for people and livestock because of their painful and irritating bite, persistent biting behavior, and blood ingestion. about 4400 tabanid species have been described; they are seasonally present in all kinds of landscapes, latitudes, and altitudes. high populations have a significant economic impact on outdoor activities, tourism, and livestock production. tabanids are also vectors of animal disease agents, including viruses, bacteria and parasites. however, tabanids ...201424727644
serosurveillance of infectious agents in equines of the central valley of costa rica.blood samples from 181 equines from the central valley of costa rica were collected in the year 2012 to determine the presence of antibodies against selected infectious agents in horses and to determine the risk factors associated with these agents. the presence of antibodies against equine infectious anemia virus (eiav), equine herpes virus 1 and 4 (ehv-1 and ehv-4), west nile virus (wnv), influenza a virus (iav), equine viral arteritis virus (evav), babesia caballi, theileria equi, neospora ca ...201426623349
equine viperin restricts equine infectious anemia virus replication by inhibiting the production and/or release of viral gag, env, and receptor via distortion of the endoplasmic reticulum.viperin is an endoplasmic reticulum (er)-associated multifunctional protein that regulates virus replication and possesses broad antiviral activity. in many cases, viperin interferes with the trafficking and budding of viral structural proteins by distorting the membrane transportation system. the lentivirus equine infectious anemia virus (eiav) has been studied extensively. in this study, we examined the restrictive effect of equine viperin (eviperin) on eiav replication and investigated the po ...201425122784
identifying the conditions under which antibodies protect against infection by equine infectious anemia virus.the ability to predict the conditions under which antibodies protect against viral infection would transform our approach to vaccine development. a more complete understanding is needed of antibody protection against lentivirus infection, as well as the role of mutation in resistance to an antibody vaccine. recently, an example of antibody-mediated vaccine protection has been shown via passive transfer of neutralizing antibodies before equine infectious anemia virus (eiav) infection of horses wi ...201426344625
equine infectious anemia virus gag assembly and export are directed by matrix protein through trans-golgi networks and cellular vesicles.gag intracellular assembly and export are very important processes for lentiviruses replication. previous studies have demonstrated that equine infectious anemia virus (eiav) matrix (ma) possesses distinct phosphoinositide affinity compared with hiv-1 ma and that phosphoinositide-mediated targeting to peripheral and internal membranes is a critical factor in eiav assembly and release. in this study, we compared the cellular assembly sites of eiav and hiv-1. we observed that the assembly of eiav ...201526637458
retinal gene therapy: current progress and future prospects.clinical trials treating inherited retinal dystrophy caused by rpe65 mutations had put retinal gene therapy at the forefront of gene therapy. both successes and limitations in these clinical trials have fueled developments in gene vectors, which continue to further advance the field. these novel gene vectors aim to more safely and efficiently transduce retinal cells, expand the gene packaging capacity of aav, and utilize new strategies to correct the varying mechanisms of dysfunction found with ...201526609316
insights into vaccine development for acquired immune deficiency syndrome from crystal structures of human immunodeficiency virus-1 gp41 and equine infectious anemia virus gp45.an effective vaccine against acquired immune deficiency syndrome is still unavailable after dozens of years of striving. the glycoprotein gp41 of human immunodeficiency virus is a good candidate as potential immunogen because of its conservation and relatively low glycosylation. as a reference of human immunodeficiency virus gp41, gp45 from equine infectious anemia virus (eiav) could be used for comparison because both wild-type and vaccine strain of eiav have been extensively studied. from stru ...201526174372
characterization of equine infectious anemia virus integration in the horse genome.human immunodeficiency virus (hiv)-1 has a unique integration profile in the human genome relative to murine and avian retroviruses. equine infectious anemia virus (eiav) is another well-studied lentivirus that can also be used as a promising retro-transfection vector, but its integration into its native host has not been characterized. in this study, we mapped 477 integration sites of the eiav strain eiavfddv13 in fetal equine dermal (fed) cells during in vitro infection. published integration ...201526102582
mice transgenic for equine cyclin t1 and elr1 are susceptible to equine infectious anemia virus infection.as a member of the tumor necrosis factor receptor (tnfr) protein superfamily, equine lentivirus receptor 1 (elr1) has been shown to be expressed in various equine cells that are permissive for equine infectious anemia virus (eiav) replication. the eiav tat protein (etat) activates transcription initiated at the viral long terminal repeat (ltr) promoter through a unique mechanism that requires the recruitment of the equine cyclin t1 (ect1) cofactor into the viral tar rna target element. in vitro ...201525928027
antibody escape kinetics of equine infectious anemia virus infection of horses.lentivirus escape from neutralizing antibodies (nabs) is not well understood. in this work, we quantified antibody escape of a lentivirus, using antibody escape data from horses infected with equine infectious anemia virus. we calculated antibody blocking rates of wild-type virus, fitness costs of mutant virus, and growth rates of both viruses. these quantitative kinetic estimates of antibody escape are important for understanding lentiviral control by antibody neutralization and in developing n ...201525878104
free-virus and cell-to-cell transmission in models of equine infectious anemia virus infection.equine infectious anemia virus (eiav) is a lentivirus in the retrovirus family that infects horses and ponies. two strains, referred to as the sensitive strain and the resistant strain, have been isolated from an experimentally-infected pony. the sensitive strain is vulnerable to neutralization by antibodies whereas the resistant strain is neutralization-insensitive. the sensitive strain mutates to the resistant strain. eiav may infect healthy target cells via free virus or alternatively, direct ...201525865935
the efficacy of elisa commercial kits for the screening of equine infectious anemia virus infection.the most used and reliable indicator of equine infectious anemia virus (eiav) infection is the detection of its specific antibodies in horse serum. in the present study, the performance of two commercial elisa tests for the detection of eiav antibodies as well as the potential advantages of their use as an eiav infection screening tool were evaluated in 302 horse serum samples. both elisa assays showed 100% diagnostic sensitivity, and 92.3-94.3% diagnostic specificity. discordant results were an ...201525735214
proteomic alteration of equine monocyte-derived macrophages infected with equine infectious anemia virus.similar to the well-studied viruses human immunodeficiency virus (hiv)-1 and simian immunodeficiency virus (siv), equine infectious anemia virus (eiav) is another member of the lentivirus genus in the family retroviridae. previous studies revealed that interactions between eiav and the host resulted in viral evolution in pathogenicity and immunogenicity, as well as adaptation to the host. proteomic analysis has been performed to examine changes in protein expression and/or modification in host c ...201525684102
double-stranded rna-specific adenosine deaminase 1 (adar1) promotes eiav replication and infectivity.adenosine deaminases that act on rna (adars) have been reported to be functional on various viruses. adar1 may exhibit antiviral or proviral activity depending on the type of virus. human immunodeficiency virus (hiv)-1 is the most well-studied lentivirus with respect to its interaction with adar1, and variable results have been reported. in this study, we demonstrated that equine adar1 (eadar1) was a positive regulator of equine infectious anemia virus (eiav), another lentivirus of the retroviri ...201525589239
structural insight into equine lentivirus receptor 1.equine lentivirus receptor 1 (elr1) has been identified as a functional cellular receptor for equine infectious anemia virus (eiav). herein, recombinant elr1 and eiav surface glycoprotein gp90 were respectively expressed in drosophila melanogaster s2 cells, and purified to homogeneity by ni-nta affinity chromatography and gel filtration chromatography. gel filtration chromatography and analytical ultracentrifugation (auc) analyses indicated that both elr1 and gp90 existed as individual monomers ...201525559821
alg-2 activates the mvb sorting function of alix through relieving its intramolecular interaction.the modular adaptor protein alix is critically involved in endosomal sorting complexes required for transport (escrt)-mediated multivesicular body (mvb) sorting of activated epidermal growth factor receptor (egfr); however, alix contains a default intramolecular interaction that renders alix unable to perform this escrt function. the alix partner protein alg-2 is a calcium-binding protein that belongs to the calmodulin superfamily. prompted by a defined biological function of calmodulin, we dete ...201527462417
prevalence of antibodies against influenza virus in non-vaccinated equines from the brazilian pantanal.the prevalence of antibodies against equine influenza virus (eiv) was determined in 529 equines living on ranches in the municipality of poconé, pantanal area of brazil, by means of the hemagglutination inhibition test, using subtype h3n8 as antigen. the distribution and possible association among positive animal and ranches were evaluated by the chi-square test, spatial autoregressive and multiple linear regression models. the prevalence of antibodies against eiv was estimated at 45.2% (95% ci ...201525351542
functional interplay between murine leukemia virus glycogag, serinc5, and surface glycoprotein governs virus entry, with opposite effects on gammaretroviral and ebolavirus glycoproteins.gammaretroviruses, such as murine leukemia viruses (mlvs), encode, in addition to the canonical gag, pol, and env proteins that will form progeny virus particles, a protein called "glycogag" (glycosylated gag). mlv glycogag contains the entire gag sequence plus an 88-residue n-terminal extension. it has recently been reported that glycogag, like the nef protein of hiv-1, counteracts the antiviral effects of the cellular protein serinc5. we have found, in agreement with prior work, that glycogag ...201627879338
comparison of antibody immune responses to different hiv-1 envelope glycoprotein mutants.the identification of immunogens is crucial for human immunodeficiency virus type 1 (hiv-1) vaccine development. in our previous study, we demonstrated that hiv-1 envelope glycoprotein mutants based on the equine infectious anemia virus (eiav)attenuated vaccine enhance immunogenicity, both for dna immunization alone and as a combined dna prime-vaccinia boost immunization. an rv144 clinical trial has demonstrated that an envelope protein boost may provide some degree of protection against hiv-1 i ...201627829329
a pilot study on interaction between donkey tetherin and eiav stains with different virulent and replication characteristics.tetherin (bst-2) is an important host restriction factor that can inhibit the release of a diverse array of enveloped viruses from infected cells. conversely, to facilitate their release and spread, many viruses have evolved various strategies to overcome the antiviral effect of tetherin in a species-specific manner. during the development of an attenuated equine infectious anemia virus (eiav) vaccine in our laboratory, we found that serial passage of a field-isolated virulent eiav strains in ho ...201627816678
s2 from equine infectious anemia virus is an infectivity factor which counteracts the retroviral inhibitors serinc5 and serinc3.the lentivirus equine infectious anemia virus (eiav) encodes the small protein s2, a pathogenic determinant that is important for virus replication and disease progression in horses. no molecular function had been linked to this accessory protein. we report that s2 can replace the activity of negative factor (nef) in hiv-1 infectivity, being required to antagonize the inhibitory activity of serine incorporator (serinc) proteins on nef-defective hiv-1. like nef, s2 excludes serinc5 from virus par ...201627803322
identification and characterization of a common b-cell epitope on eiav capsid proteins.the equine infectious anemia virus (eiav) capsid protein (p26) is one of the major immunogenic proteins during eiav infection and is widely used for the detection of eiav antibodies in horses. however, few reports have described the use of eiav-specific monoclonal antibodies (mabs) in etiological and immunological detection. previously, we developed an antigen capture enzyme-linked immunosorbent assay (ac-elisa) for the quantification of the eiav p26 protein level. however, the epitopes recogniz ...201627660181
health and epidemiological approaches of trypanosoma evansi and equine infectious anemia virus in naturally infected horses at southern pantanal.equine infectious anemia virus (eiav) and trypanossoma evansi are endemic in brazilian pantanal biome, an important area for livestock production. in this sense, we evaluated the epidemiological single and co-infection effects of t. evansi and eiav in naturally infected horses in the southern pantanal wetland by serological tests and hematological assays. both higher seroprevalence and heath poor condition of the sampled animals were associated with differences in horse management between farms. ...201627497875
optimizing transgene configuration and protein fusions to maximize dopamine production for the gene therapy of parkinson's disease.pharmacological dopamine replacement therapies provide the most well-established treatments for parkinson's disease (pd). however, these long-term treatments can lead to motor complications and off-target effects. prosavin(®), a lentiviral vector (lv)-based gene therapy approach aimed at restoring local and continuous dopamine production, through delivery of three enzymes in the dopamine biosynthesis pathway, was demonstrated to be safe and well-tolerated in a phase i/ii clinical study of patien ...201627470285
double-stranded-rna-specific adenosine deaminase 1 (adar1) is proposed to contribute to the adaptation of equine infectious anemia virus from horses to donkeys.equine infectious anemia virus (eiav) is a member of the genus lentivirus of the family retroviridae. horses are the most susceptible equids to eiav infection and are therefore the primary hosts of this virus. in contrast, infected donkeys do not develop clinically active equine infectious anemia (eia). this phenomenon is similar to what has been observed with hiv-1, which fails to induce aids in non-human primates. interestingly, shen et al. developed a donkey-tropic pathogenic virus strain (ei ...201627383210
equine schlafen 11 restricts the production of equine infectious anemia virus via a codon usage-dependent mechanism.human schlafen11 is a novel restriction factor for hiv-1 based on bias regarding relative synonymous codon usage (rscu). here, we report the cloning of equine schlafen11 (eslfn11) and the characteristics of its role in restricting the production of equine infectious anemia virus (eiav), a retrovirus similar to hiv-1. overexpression of eslfn11 inhibited eiav replication, whereas knockdown of endogenous eslfn11 by sirna enhanced the release of eiav from its principal target cell. notably, although ...201627200480
serologically silent, occult equine infectious anemia virus (eiav) infections in horses.molecular and serological techniques for equine infectious anemia virus (eiav) diagnosis were compared using samples from 59 clinically normal horses stabled on five farms in the santa fe province of argentina. of these 26 (44.1%) were positive in official agid tests and/or gp45/gp90-based elisa. surprisingly 18 of the 33 seronegative horses were positive in a pcr against viral sequences encoding gp45 (pcr-positive/agid-negative) with all but one remaining eiav-antibody negative throughout a two ...201627066707
validation according to oie criteria of a monoclonal, recombinant p26-based, serologic competitive enzyme-linked immunosorbent assay as screening method in surveillance programs for the detection of equine infectious anemia virus antibodies.the italian national reference center for equine infectious anemia (craie; rome, italy) developed and validated a monoclonal, recombinant p26-based competitive enzyme-linked immunosorbent assay (celisa) for the detection of eia virus antibodies employing the 2010 criteria of the world organization for animal health (oie). the following parameters were evaluated: cutoff values, repeatability, reproducibility, concordance, analytical sensitivity (se), absolute analytical specificity (sp), and diag ...201626965228
genetic evolution during the development of an attenuated eiav vaccine.the equine infectious anemia virus (eiav) vaccine is the only attenuated lentiviral vaccine applied on a large scale that has been shown to be effective in controlling the prevalence of eia in china. this vaccine was developed by successive passaging of a field-isolated virulent strain in different hosts and cultivated cells. to explore the molecular basis for the phenotype alteration of this vaccine strain, we systematically analyzed its genomic evolution during vaccine development.201626842878
infection with equine infectious anemia virus vaccine strain eiavdlv121 causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response.the live equine infectious anemia virus (eiav) vaccine strain eiavdlv121 was developed by in vitro attenuation of a virulent strain, eiavln40, in the 1970s, and it has been demonstrated to induce protective immunity under laboratory and natural eiav infection conditions. the detailed biological features of this attenuated virus remain to be further investigated. experimental inoculation with eiavdlv121 did not result in clinical symptoms even with immunosuppressive treatment in our previous stud ...201626832985
structural illumination of equine mhc class i molecules highlights unconventional epitope presentation manner that is evolved in equine leukocyte antigen alleles.mhc class i (mhc i)-restricted virus-specific ctls are implicated as critical components in the control of this naturally occurring lentivirus and in the protective immune response to the successfully applied attenuated equine infectious anemia virus vaccine in the horse. nevertheless, the structural basis for how the equine mhc i presents epitope peptides remains unknown. in this study, we investigated the binding of several equine infectious anemia virus-derived epitope peptides by the ability ...201626764037
horses naturally infected with eiav harbor 2 distinct su populations but are monophyletic with respect to in.equine infectious anemia virus (eiav) causes lifelong infections ranging from acutely fatal, to chronic, to asymptomatic. within infected animals, eiav is found as a quasispecies. many experimental studies on eiav, carried out in the u.s. over the past 70 years, have used either the highly virulent wyoming (eiavwyo) field strain or various derivatives of that strain. these infections have provided insights into the variety of genetic changes that accumulate in the env gene and ltr in experimenta ...201626739458
lentiviral vector gene transfer of endostatin/angiostatin for macular degeneration (gem) study.neovascular age-related macular degeneration (nvamd) is a prevalent cause of vision loss. intraocular injections of vegf-neutralizing proteins provide benefit, but many patients require frequent injections for a prolonged period. benefits are often lost over time due to lapses in treatment. new treatments that sustain anti-angiogenic activity are needed. this study tested the safety and expression profile of a lentiviral equine infectious anemia virus (eiav) vector expressing endostatin and angi ...201727710144
covalent conjugation of the equine infectious anemia virus gag with sumo.the conjugation of small ubiquitin-like modifier (sumo) to the target protein, namely, sumoylation, is involved in the regulation of many important biological events including host-pathogen interaction. some viruses have evolved to exploit the host sumoylation machinery to modify their own protein. retroviral gag protein plays critical roles in the viral life cycle. the hiv-1 p6 and the moloney murine leukemia virus ca have been reported to be conjugated with sumo. in this study, we report for t ...201728342872
feline immunodeficiency virus evolutionarily acquires two proteins, vif and protease, capable of antagonizing feline apobec3.the interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. mammalian genes encode apolipoprotein b mrna-editing enzyme catalytic polypeptide-like 3 (apobec3) proteins, which act as intrinsic restriction factors against lentiviruses. to overcome apobec3-mediated anti-viral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (vif), and vif degrades host apobec3 proteins via ...201728331087
characterization of isolates of equine infectious anemia virus in brazil.equine infectious anemia is an important infectious disease that affects equids worldwide. control of the disease is currently based on detection of anti-p26 eiav by agar gel immunodiffusion (agid). in this work, 62 animals were examined by agid and nested-pcr using primers for the gag gene. fifty-three samples (85.5%) were positive by nested-pcr, whereas only 33 samples (53%) were positive for agid. fifteen amplicons obtained by nested-pcr were sequenced and the aligned results subjected to phy ...201727896562
the small-molecule 3g11 inhibits hiv-1 reverse transcription.the small-molecule 6-(tert-butyl)-4-phenyl-4-(trifluoromethyl)-1h,3h-1,3,5-triazin-2-one (3g11) inhibits hiv-1 replication in the human t cell line mt-2. here, we showed that 3g11 specifically and potently blocks hiv-1 infection. by contrast, 3g11 did not block other retroviruses such as hiv-2, simian immunodeficiency virus (sivmac ), bovine immunodeficiency virus, feline immunodeficiency virus, equine infectious anemia virus, n-tropic murine leukemia virus, b-tropic murine leukemia virus, and m ...201727748043
molecular characterization of bovine leukemia virus from moldovan dairy cattle.bovine leukemia virus (blv) is the causative agent of enzootic bovine leukosis (ebl), a disease that has worldwide distribution. whilst it has been eradicated in most of western europe and scandinavia, it remains a problem in other regions, particularly eastern europe and south america. for this study, in 2013, 24 cattle from three farms in three regions of moldova were screened by elisa and nested pcr. of these cattle, 14 which were pcr positive, and these were molecularly characterized based o ...201728213870
equine infectious anemia prevalence in feral donkeys from northeast brazil.equine infectious anemia virus (eiav) is an important cause of morbidity and mortality throughout the world. although the virus infects all members of the equidae the vast majority of studies have been conducted in horses (equus caballus) with comparatively little information available for other equid species. brazil has one of the most abundant donkey (e. asinus) populations of any nation although the economic importance of these animals is declining as transportation becomes increasingly mecha ...201728460747
distinct ventral pallidal neural populations mediate separate symptoms of depression.major depressive disorder (mdd) patients display a common but often variable set of symptoms making successful, sustained treatment difficult to achieve. separate depressive symptoms may be encoded by differential changes in distinct circuits in the brain, yet how discrete circuits underlie behavioral subsets of depression and how they adapt in response to stress has not been addressed. we identify two discrete circuits of parvalbumin-positive (pv) neurons in the ventral pallidum (vp) projecting ...201728689640
detection of west nile virus and other common equine viruses in three locations from the leeward islands, west indies.equines in the west indies are used for recreational purposes, tourism industry, racing and agriculture or can be found in feral populations. little is known in the caribbean basin about the prevalence of some major equine infectious diseases, some with zoonotic potential, listed as reportable by the oie. our objective was to study the prevalence of antibodies for west nile virus (wnv), equine herpes virus-1 and 4 (ehv-1 and ehv-4), equine influenza (ei), equine viral arteritis (eva) and equine ...201728648789
nonsynonymous changes of equine lentivirus receptor-1 (elr1) gene in amino acids involved in the interaction with equine infectious anemia virus (eiav).equine lentivirus receptor-1 (elr1) has been characterized as the specific functional receptor that mediates equine infectious anemia virus (eiav) entrance to horse macrophages. this receptor is tumor necrosis factor receptor superfamily member 14 (tnfrsf14). the aim of this study was to investigate the occurrence of allelic variants in the coding sequence of equine tnfrsf14 gene by screening for single-nucleotide polymorphisms (snps) in different equine populations. forty seven horse samples we ...201728500993
surveillance of the equine infectious anemia virus in eastern and central saudi arabia during 2014-2016.equine infectious anemia virus (eiav) is one of the most important threats to the equine industry globally. this is due to the poor performance of the affected horses, which requires euthanization of the infected animals upon the infection confirmation. infected animals remain carriers throughout their life. eiav infection has been reported in many parts of the world, including north america, europe, asia, and africa. however, the eiav status is never assessed in horses in the gulf area, especia ...201931327910
a potent postentry restriction to primate lentiviruses in a yinpterochiropteran bat.bats are primary reservoirs for multiple lethal human viruses, such as ebola, nipah, hendra, rabies, severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome-related coronavirus (mers-cov), and, most recently, sars-cov-2. the innate immune systems of these immensely abundant, anciently diverged mammals remain insufficiently characterized. while bat genomes contain many endogenous retroviral elements indicative of past exogenous infections, little is known about ...202032934084
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