Equine Infectious Anemia (EIA) is a viral disease affecting horses, caused by the Equine Infectious Anemia Virus (EIAV), a member of the Lentivirus genus. The disease is characterized by intermittent fever, anemia, edema, and weight loss, though some horses may remain asymptomatic carriers. Transmission occurs primarily through blood-feeding insects such as horseflies and deerflies, or through contaminated instruments. EIA is diagnosed using serological tests, with the Coggins test being a commonly used method for detection. There is no vaccine or cure for EIA, and management primarily focuses on prevention and control measures to limit transmission. This page assembles peer-reviewed studies and scholarly articles that explore the pathogenesis, epidemiology, diagnostic methods, and management strategies related to Equine Infectious Anemia.
Ricotti S, Garcia MI, Veaute C, Bailat A, Lucca E, Cook RF, Cook SJ, Soutullo A.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 year observation period. The gp45 PCR results are supported by fact that 7/18 of these horses were ...
Wang XF, Lin YZ, Li Q, Liu Q, Zhao WW, Du C, Chen J, Wang X, Zhou JH.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. Results: Sequence analysis revealed that the genetic distance between the wild-type strain and six representati...
West Nile virus in Europe and the USA. Evidence that the spread of vesicular stomatitis in the USA is beginning to slow. Summary of UK surveillance testing, July to September 2015 These are among matters discussed in the most recent quarterly equine disease surveillance report, prepared by Defra, the Animal Health Trust and the British Equine Veterinary Association.
Liu Q, Ma J, Wang XF, Xiao F, Li LJ, Zhang JE, Lin YZ, Du C, He XJ, Wang X, Zhou JH.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 studies. Here, we further investigated whether the replication of the vaccine strain EIAVDLV121 in exper...
Cervantes DT, Ball JM, Edwards J, Payne S.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 experimentally infected horses. In the current study, we obtained EIAV sequences from blood samples collected f...
Zhang Z, Ma J, Zhang X, Su C, Yao QC, Wang X.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 particles occurred on interior cellular membranes, while HIV-1 was targeted to the plasma membrane (...
Issel CJ, Foil LD.There is no credible evidence that the lentivirus that causes equine infectious anaemia (EIA) replicates in invertebrates. The virus persistently infects its equid hosts and is often present in blood in significant quantities. Blood-feeding arthropods thus have the potential to transfer the virus between hosts, especially if their feeding on the first host is interrupted and immediately continued on a second host. The general details and dynamics of mechanical transmission are included in this paper, as this agent presents an excellent model. Mechanical transmission can be effectively controll...
Liu Q, Wang XF, Ma J, He XJ, Wang XJ, Zhou JH.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 sites of EIAV and HIV-1 in the human genome were also analyzed as references. Our results demonstrat...
Schwartz EJ, Nanda S, Mealey RH.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 NAb-eliciting vaccine strategies.
Allen LJ, Schwartz EJ.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, directly from an infected target cell through cell-to-cell transfer. The proportion of transmission from f...
Du C, Liu HF, Lin YZ, Wang XF, Ma J, Li YJ, Wang X, Zhou JH.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 cells infected with viruses and has revealed useful information for virus-host interactions. In this ...
Alvarez I, Cipolini F, Wigdorovitz A, Trono K, Barrandeguy ME.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 analyzed by immunoblot. The results showed that both ELISA tests are very efficient at detecting EIAV ...
Kuhar U, Malovrh T.The equine infectious anaemia virus (EIAV), which belongs to the Retroviridae family, infects equids almost worldwide. Every year, sporadic EIAV cases are detected in Slovenia. Objective: To characterise the Slovenian EIAV strains in the p15 gag gene region phylogenetically in order to compare the Slovenian EIAV strains with EIAV strains from abroad, especially with the recently published European strains. Methods: Cross-sectional study using material derived from post mortem examination. Methods: In total, 29 EIAV serologically positive horses from 18 different farms were examined in this stu...
Cruz F, Fores P, Ireland J, Moreno MA, Newton R.No cases of equine infectious anaemia (EIA) have been reported in Spain since 1983. Factors that could increase the risk of reintroducing equine infectious anaemia virus (EIAV) into Spain include the recent occurrence of the disease in Europe and the absence of compulsory serological testing before importation into Spain. Objective: Given the importance of the Spanish Purebred (SP) horse breeding industry in Spain, the aim of this cross-sectional study was to provide evidence of freedom from EIAV in SP stud farms in Central Spain. Methods: Serum samples from 555 SP horses, collected between Se...
Jiménez D, Romero-Zuñiga JJ, Dolz G.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 caninum and Chlamydia abortus was determined using commercial assays, and risk factors associated with...
Wang XF, Wang S, Liu Q, Lin YZ, Du C, Tang YD, Na L, Wang X, Zhou JH.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% (10 of 68 residues) of the stable amino acid mutations occurred longitudinally in S2 during a 150-...
Issel CJ, Cook RF, Mealey RH, Horohov DW.In the absence of an effective vaccine, the success of the test and removal approach for the control of equine infectious anemia (EIA) cannot be overstated, at least in those areas where testing has been traditionally routine. This article addresses 4 main aspects: what has been learned about EIA virus, host control of its replication, and inapparent carriers; international status regarding the control of EIA; diagnostic and laboratory investigation; and reducing the spread of blood-borne infections by veterinarians. An attempt is made to put these issues into practical contemporary perspectiv...
Gaíva e Silva L, Borges AM, Villalobos EM, Lara Mdo C, Cunha EM, de Oliveira AC, Braga IA, Aguiar DM.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 30.2 - 61.1%) with titers ranging from 20 to 1,280 HAU. Seropositive equines were found on 92.0% of...
Yin X, Guo M, Gu Q, Wu X, Wei P, Wang X.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 the host-virus relationship. The host range of EIAV is reported to include all members of the Equidae ...
Dong J, Cook FR, Haga T, Horii Y, Norimine J, Misawa N, Goto Y, Zhu W.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 terminal repeats (LTRs) and structural genes. This analysis represents a significant step forward in increa...
Tang YD, Na L, Zhu CH, Shen N, Yang F, Fu XQ, Wang YH, Fu LH, Wang JY, Lin YZ, Wang XF, Wang X, Zhou JH, Li CY.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 possible molecular basis of this restriction to obtain insights into the effect of this cellular facto...
Liu C, Cook SJ, Craigo JK, Cook FR, Issel CJ, Montelaro RC, Horohov DW.Unlike other lentiviruses, EIAV replication can be controlled in most infected horses leading to an inapparent carrier state free of overt clinical signs which lasts for many years. While the resolution of the initial infection is correlated with the appearance of virus specific cellular immune responses, the precise immune mechanisms responsible for control of the infection are not yet identified. Since the virus undergoes rapid mutation following infection, the immune response must also adapt to meet this challenge. We hypothesize that this adaptation involves peptide-specific recognition sh...
Ma J, Wang SS, Lin YZ, Liu HF, Liu Q, Wei HM, Wang XF, Wang YH, Du C, Kong XG, Zhou JH, Wang X.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 in equine monocyte-derived macrophages (eMDM) that EIAVFDDV13, a Chinese attenuated EIAV strain, indu...
Haas L.This article combines essential facts of equine infectious anemia. Beside etiology and epidemiology, emphasis is put on the clinical course and laboratory diagnosis. Finally, control measures and prophylactic issues are discussed.
Schwartz EJ, Smith RJ.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 with severe combined immunodeficiency (SCID). Viral dynamic modeling of antibody protection from EIAV ...
Mangana-Vougiouka O, Boutsini S, Ntousi D, Patakakis M, Orfanou E, Zafiropoulou K, Dilaveris D, Panagiotatos D, Nomikou K.During the period 2001 to 2008, a total of 7,872 equine sera were tested at the Centre of Veterinary Institutes of Athens. Antibodies against seven infectious diseases of equids were determined: equine infectious anaemia (EIA), African horse sickness (AHS), equine viral arteritis (EVA), West Nile encephalitis (WNE), glanders, piroplasmosis and dourine. Tests for the four viral diseases found 4.5% seropositivity for EIA, 0% for AHS, 3.3% for EVA and 4% for WNE. All sera tested for glanders antibodies were negative. Tests for piroplasmosis detected antibodies against T. equi and B. caballi in 12...
Du J, Wang X, Ma J, Wang J, Qin Y, Zhu C, Liu F, Shao Y, Zhou J, Qiao W, Liu X.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 lentiviruses for which an effective vaccine has been successfully developed. The attenuated vaccine strai...
Tagmyer TL, Craigo JK, Cook SJ, Even DL, Issel CJ, Montelaro RC.A highly effective attenuated equine infectious anemia virus (EIAV) vaccine (EIAV(D9)) capable of protecting 100% of horses from disease induced by a homologous Env challenge strain (EIAV(PV)) was recently tested in ponies to determine the level of protection against divergent Env challenge strains (J. K. Craigo, B. S. Zhang, S. Barnes, T. L. Tagmyer, S. J. Cook, C. J. Issel, and R. C. Montelaro, Proc. Natl. Acad. Sci. USA 104:15105-15110, 2007). An inverse correlation between challenge strain Env variation and vaccine protection from disease was observed. Given the striking differences in pro...
Zhang W, Lonning SM, McGuire TC.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 peptides of 16 to 25 amino acids, peptides containing at least 12 Gag CTL epitopes recognized by virus-st...
Alexandersen S, Carpenter S.The polymerase chain reaction was used to amplify and clone parts of the envelope gene and overlapping S3 open reading frame, thought to encode rev, of the virulent in vivo-derived Th-1 isolate of equine infectious anemia virus (EIAV). The results indicated that EIAV consists of a heterogeneous mixture of genotypes present at the first febrile cycle after initial infection. We showed that the Th-1 isolate apparently contains nondefective genotypes as well as types which have transmembrane protein truncations or are rev deficient. Furthermore, we could confirm the presence of a hypervariable re...
Hammond SA, Raabe ML, Issel CJ, Montelaro RC.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 comparison of EIAV envelope-specific antibody responses elicited by attenuated, inactivated whole virus and ...
Provitera P, Bouamr F, Murray D, Carter C, Scarlata S.Human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) are closely related lentiviruses that infect immune cells, but their pathogenesis differ. Localization to the cytosolic leaflet of the plasma membrane is critical for replication of both viruses. This localization is accomplished through the matrix (MA) domain of the Gag precursor protein. In HIV-1, association of MA to anionic membranes appears to be primarily driven by a linear cluster of basic residues in the MA domain and an N-myristoylation signal. Interestingly, the MA protein of EIAV does not contain either of ...
Lin YZ, Shen RX, Zhu ZY, Deng XL, Cao XZ, Wang XF, Ma J, Jiang CG, Zhao LP, Lv XL, Shao YM, Zhou JH.The EIAV (equine infectious anemia virus) multi-species attenuated vaccine EIAV(DLV121) successfully prevented the spread of equine infectious anemia (EIA) in China in the 1970s and provided an excellent model for the study of protective immunity to lentiviruses. In this study, we compared immune responses induced by EIAV(DLV121) to immunity elicited by the virulent EIAV(LN40) strain and correlated immune responses to protection from infection. Horses were randomly grouped and inoculated with either EIAV(DLV121) (Vaccinees, Vac) or a sublethal dose of EIAV(LN40) (asymptomatic carriers, Car). C...
McGuire TC, Van Hoosier GL, Henson JB.The role of non-complement-fixing anti-equine infectious anemia (EIA) antibody in the conversion of complement fixation (CF) tests from positive to negative in EIA-infected horses was investigated. Complement-fixation inhibition (CFI) tests demonstrated antibodies in sera that were CF negative. These antibodies would bind to antigen, but would not fix complement. The inhibiting antibodies were isolated and shown to be IgG(T) by immunoelectrophoresis and immunodiffusion against monospecific anti-IgG(T) antisera. Separation of immunoglobulins from affected horse sera by DEAE cellulose chromatogr...
Craigo JK, Leroux C, Howe L, Steckbeck JD, Cook SJ, Issel CJ, Montelaro RC.The genetic variation of equine infectious anaemia virus (EIAV) clearly affects the antigenic properties of the viral envelope; however, effects on immunogenicity remain undefined, although widely assumed. Here, the immunogenicity is reported of a novel, neutralization-resistant, pony-isolate envelope EIAV(PV564DeltaPND) that contains a 14-residue deletion in the designated principal neutralizing domain (PND) of the gp90 protein. Two ponies inoculated with a chimeric virus, EIAV(DeltaPND), containing the EIAV(PV564DeltaPND) envelope in a reference provirus strain, remained asymptomatic through...
Lichtenstein DL, Issel CJ, Montelaro RC.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 disease episode from two ponies infected with EIAV PV. Overall sequence variation within gp90 was lo...
Howe L, Leroux C, Issel CJ, Montelaro RC.Equine infectious anemia virus (EIAV) infection of horses is characterized by well-defined waves of viremia associated with the sequential evolution of distinct viral populations displaying extensive envelope gp90 variation; however, a correlation of in vivo envelope evolution with in vitro serum neutralization phenotype remains undefined. Therefore, the goal of the present study was to utilize a previously defined panel of natural variant EIAV envelope isolates from sequential febrile episodes to characterize the effects of envelope variation during persistent infection on viral neutralizatio...
Wang XF, Lin YZ, Li Q, Liu Q, Zhao WW, Du C, Chen J, Wang X, Zhou JH.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. Results: Sequence analysis revealed that the genetic distance between the wild-type strain and six representati...
Taube R, Fujinaga K, Irwin D, Wimmer J, Geyer M, Peterlin BM.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 from horse and dog and demonstrate that their N-terminal 300 residues rescue the transactivation of Ta...
Mealey RH, Fraser DG, Oaks JL, Cantor GH, McGuire TC.Acute infection with equine infectious anemia virus (EIAV), a lentivirus of horses, results in a persistent high-level viremia in Arabian foals affected with severe combined immunodeficiency (SCID). This observation argues against the idea that the transient nature of acute lentiviral viremia is solely a function of viral population dynamics. To extend these studies, EIAV-specific immune reconstitution was attempted prior to EIAV challenge in two SCID foals, using adoptively transferred virus-stimulated lymphocytes derived from persistently EIAV-infected half sibling donors. Following transfer...
Baccam P, Thompson RJ, Li Y, Sparks WO, Belshan M, Dorman KS, Wannemuehler Y, Oaks JL, Cornette JL, Carpenter S.Lentiviruses exist in vivo as a population of related, nonidentical genotypes, commonly referred to as quasispecies. The quasispecies structure is characteristic of complex adaptive systems and contributes to the high rate of evolution in lentiviruses that confounds efforts to develop effective vaccines and antiviral therapies. Here, we describe analyses of genetic data from longitudinal studies of genetic variation in a lentivirus regulatory protein, Rev, over the course of disease in ponies experimentally infected with equine infectious anemia virus. As observed with other lentivirus data, t...
Zheng YH, Nakaya T, Sentsui H, Kameoka M, Kishi M, Hagiwara K, Takahashi H, Kono Y, Ikuta K.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 limited number of nucleotide positions, consisting of insertions and duplications in the gp90 princi...
Sponseller BA, Sparks WO, Wannemuehler Y, Li Y, Antons AK, Oaks JL, Carpenter S.The principal neutralizing domain (PND) of equine infectious anemia virus (EIAV) is located in the V3 region of SU. Genetic variation in the PND is considered to play an important role in immune escape and EIAV persistence; however, few studies have characterized genetic variation in SU during the inapparent stage of disease. To better understand the mechanisms of virus persistence, we undertook a longitudinal study of SU variation in a pony experimentally inoculated with the virulent EIAV(Wyo). Viral RNA isolated from the inoculum and from sequential sera samples was amplified by RT-PCR, clon...
Lin YZ, Cao XZ, Li L, Li L, Jiang CG, Wang XF, Ma J, Zhou JH.The attenuated equine infectious anemia virus (EIAV) vaccine was the first attenuated lentivirus vaccine to be used in a large-scale application and has been used to successfully control the spread of equine infectious anemia (EIA) in China. To better understand the potential role of cytokines in the pathogenesis of EIAV infection and resulting immune response, we used branched DNA technology to compare the mRNA expression levels of 12 cytokines and chemokines, including IL-1α, IL-1β, IL-4, IL-10, TNF-α, IFN-γ, IP-10, IL-8, MIP-1α, MIP-1β, MCP-1, and MCP-2, in equine monocyte-derived mac...
Belshan M, Park GS, Bilodeau P, Stoltzfus CM, Carpenter S.In 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 splicing enhancer (ESE) was required for exon 3 recognition, and the addition of Rev inhibited exon 3 sp...
McGuire TC, Leib SR, Mealey RH, Fraser DG, Prieur DJ.Control of a naturally occurring lentivirus, equine infectious anemia virus (EIAV), occurs in most infected horses and involves MHC class I-restricted, virus-specific CTL. Two minimal 12-aa epitopes, Env-RW12 and Gag-GW12, were evaluated for presentation by target cells from horses with an equine lymphocyte Ag-A1 (ELA-A1) haplotype. Fifteen of 15 presented Env-RW12 to CTL, whereas 11 of 15 presented Gag-GW12. To determine whether these epitopes were presented by different molecules, MHC class I genes were identified in cDNA clones from Arabian horse A2152, which presented both epitopes. This h...
Archer BG, Crawford TB, McGuire TC, Frazier ME.Equine infectious anemia (EIAV) is shown to have an associated RNA-instructed DNA polymerase similar in its cofactor requirements and reaction conditions to the RNA tumor virus DNA polymerases. Demonstrating this DNA polymerase activity requires a critical concentration of a nonionic detergent, all four deoxyribonucleoside triphosphates, and a divalent metal ion. The reaction is sensitive to RNase, and a substantial fraction of the FNA synthesized is complementary to viral RNA. The detection of a complex of tritium-labeled polymerase product DNA-template RNA, which sedimented at 60S to 70S, pr...
Whetter L, Archambault D, Perry S, Gazit A, Coggins L, Yaniv A, Clabough D, Dahlberg J, Fuller F, Tronick S.A full-length molecular clone of equine infectious anemia virus (EIAV) was isolated from a persistently infected canine fetal thymus cell line (Cf2Th). Upon transfection of equine dermis cells, the clone, designated CL22, yielded infectious EIAV particles (CL22-V) that replicated in vitro in both Cf2Th cells and an equine dermis cell strain. Horses infected with CL22-V developed an antibody response to viral proteins and possessed viral DNA in peripheral blood mononuclear cells, as determined by polymerase chain reaction assays. In addition, horses infected with CL22-V became persistently infe...
Pedersen NC.Lentiviruses are associated with persistent infection and chronic
disease in three major species of livestock—horses, sheep, and goats.
Another lentivirus named bovine immunodeficiency virus (BIV) recently has been described (Gonda et al., 1987). It is a Visna-like virus that was originally isolated over a decade ago from cattle with
persistent lymphocytosis, lymphadenopathy, weakness, emaciation,
and central nervous system (CNS) lesions (Van der Maaten et al,
1972). There is very little information on the epidemiology, clinical
manifestations, or importance of bovine lentivirus infect...
Brindley MA, Maury W.Entry of wild-type lentivirus equine infectious anemia virus (EIAV) into cells requires a low-pH step. This low-pH constraint implicates endocytosis in EIAV entry. To identify the endocytic pathway involved in EIAV entry, we examined the entry requirements for EIAV into two different cells: equine dermal (ED) cells and primary equine endothelial cells. We investigated the entry mechanism of several strains of EIAV and found that both macrophage-tropic and tissue culture-adapted strains utilize clathrin-coated pits for entry. In contrast, a superinfecting strain of EIAV, EIAV(vMA-1c), utilizes ...
Cook RF, Berger SL, Rushlow KE, McManus JM, Cook SJ, Harrold S, Raabe ML, Montelaro RC, Issel CJ.Serial passage of the prototype (PR) cell-adapted Wyoming strain of equine infectious anemia virus (EIAV) in fetal donkey dermal (FDD) rather than fetal horse (designated fetal equine kidney [FEK]) cell cultures resulted in the generation of a variant virus strain which produced accelerated cytopathic effects in FDD cells and was 100- to 1,000-fold more sensitive to neutralizing antibodies than its parent. This neutralization-sensitive variant was designated the FDD strain. Although there were differences in glycosylation between the PR and FDD strains, passage of the FDD virus in FEK cells di...
Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, Issel C, Montelaro RC.Among the diverse experimental vaccines evaluated in various animal lentivirus models, live attenuated vaccines have proven to be the most effective, thus providing an important model for examining critical immune correlates of protective vaccine immunity. We previously reported that an experimental live attenuated vaccine for equine infectious anemia virus (EIAV), based on mutation of the viral S2 accessory gene, elicited protection from detectable infection by virulent virus challenge (F. Li et al., J. Virol. 77:7244-7253, 2003). To better understand the critical components of EIAV vaccine e...
Gustchina A, Kervinen J, Powell DJ, Zdanov A, Kay J, Wlodawer A.Equine infectious anemia virus (EIAV), the causative agent of infectious anemia in horses, is a member of the lentiviral family. The virus-encoded proteinase (PR) processes viral polyproteins into functional molecules during replication and it also cleaves viral nucleocapsid protein during infection. The X-ray structure of a complex of the 154G mutant of EIAV PR with the inhibitor HBY-793 was solved at 1.8 A resolution and refined to a crystallographic R-factor of 0.136. The molecule is a dimer in which the monomers are related by a crystallographic twofold axis. Although both the enzyme and t...
Sellon DC.The ability of EIAV to persistently infect horses in the face of a profound immune response by the host makes it a potentially devastating disease for the horse population of the United States. Its ability to evade host immune defenses by lying dormant in apparently healthy animals and by rapidly changing its antigenic determinants is proving to be a major obstacle to vaccine development. Because most infected horses appear clinically normal and a large proportion of horses in this country remain untested, the virus is not likely to be eradicated in the near future. Yet, for the same reason, b...
Tumas DB, Hines MT, Perryman LE, Davis WC, McGuire TC.The immune control of chronic equine infectious anaemia (EIA) lentiviral infection was investigated by specifically depleting CD5+ T lymphocytes in vivo with monoclonal antibody (MAb) or by immunosuppression with corticosteroids. MAb was given at 25 to 50 mg/day intravenously for 11 days. Murine IgG1 anti-equine CD2 MAb (n = 2 horses) or IgG1 (n = 2) and IgG2a control MAb (n = 2 normal; 2 EIA-infected) did not deplete CD2+ T lymphocytes in horses. Horses given murine IgG2a anti-CD5 MAb HB19A (n = 4 normal; 5 EIA-infected) had depletion of peripheral blood CD5+ T lymphocytes during treatment. T...
Cook SJ, Cook RF, Montelaro RC, Issel CJ.Most in vivo studies with equine infectious anemia virus (EIAV) have been performed in horses and ponies (Equus caballus) with little published information available detailing the clinical responses of donkeys (Equus asinus) to infection with this virus. Consequently, donkeys were inoculated with two strains of EIAV (EIAV(PV) and EIAV(WY)) which have been documented to produce disease in E. caballus. Four ponies, 561, 562, 564 and 567 and two donkeys, 3 and 5 were infected with EIAV(PV) and one horse (94-10) and one donkey (4) were infected with EIAV(WY). Although the horse and ponies all expe...
