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.
Resende CF, Santos AM, Cook RF, Victor RM, Câmara RJF, Gonçalves GP, Lima JG, Maciel E Silva AG, Leite RC, Dos Reis JKP.Marajó Island, within in the Amazon River Delta, supports numerous bands of feral equids including the genetically distinct Marajoara horses. Approximately 40% of the equids on the island are infected with Equine infectious anemia virus (EIAV). This high seropositivity rate coupled with the need to preserve rare breeds such as the Marajoara horse precludes euthanasia as the primary means for controlling EIAV in this region. In the absence of iatrogenic transmission, spread of this lentivirus is mediated primarily by hematophagous insects, whose year-round prevalence on the island is supported...
Cardenas NC, Sanchez F, Lopes FPN, Machado G.Most animal disease surveillance systems concentrate efforts in blocking transmission pathways and tracing back infected contacts while not considering the risk of transporting animals into areas with elevated disease risk. Here, we use a suite of spatial statistics and social network analysis to characterize animal movement among areas with an estimated distinct risk of disease circulation to ultimately enhance surveillance activities. Our model utilized equine infectious anemia virus (EIAV) outbreaks, between-farm horse movements, and spatial landscape data from 2015 through 2017. We related...
Abisheva A, Abishov A, Khairullaeva K, Shynybayev K, Kalissynov B, Maikhin K, Kydyrmanov A, Karamendin K, Valdovska A, Syrym N.Equine rhinopneumonitis is an acute, highly contagious disease found virtually worldwide. The purpose of the studies presented in this paper is to develop a technology for the manufacture of a cell-derived equine rhinopneumonitis vaccine, as well as to assess the safety and immunogenicity of the newly developed vaccine in laboratory animals model. The object of the studies was the AK-2011 strain isolated from the horses suffering from rhinopneumonitis during an outbreak of abortions. The viability of the AK-2011 strain was assessed using a continuous line of calf trachea cells, a continuous li...
Russi RC, Garcia L, Cámara MS, Soutullo AR.Equine infectious anaemia (EIA) is controlled by the identification of seropositive animals. The official diagnostic method is the agar gel immunodiffusion (AGID) test, which detects antibodies against a viral core protein (p26). Although AGID is inexpensive and specific, the report of results takes considerable time and the test has low analytical sensitivity. Objective: To validate our in-house indirect ELISA , following the World Organization of Animal Health (OIE) criteria. Methods: Test validation. Methods: Synthetic peptides gp90 and gp45 were used as antigens in ELISA . Tests used for v...
Schwartz EJ, Costris-Vas C, Smith SR.Equine infectious anemia virus (EIAV) is a lentivirus similar to HIV that infects horses. Clinical and experimental studies demonstrating immune control of EIAV infection hold promise for efforts to produce an HIV vaccine. Antibody infusions have been shown to block both wild-type and mutant virus infection, but the mutant sometimes escapes. Using these data, we develop a mathematical model that describes the interactions between antibodies and both wild-type and mutant virus populations, in the context of continual virus mutation. The aim of this work is to determine whether repeated vaccinat...
Costa VMD, Cursino AE, Franco Luiz APM, Braz GF, Cavalcante PH, Souza CA, Simplício KMMG, Drumond BP, Lima MT, Teixeira BM, Kroon EG.Equine infectious anemia (EIA) is listed by the World Organization for Animal Health (OIE) as one of the equine diseases that must be notified. No effective treatment or vaccine is available. EIA control is based on segregation and euthanasia of positive equids. The disease is caused by the equine infectious anemia virus (EIAV), a member of the genus Lentivirus of the Retroviridae family. Despite the importance of this disease in equids, EIA has been poorly studied in donkeys (Equus asinus). We evaluate the sanitary conditions related to EIAV in donkeys from a shelter of abandoned animals capt...
Equine infectious anemia (EIA) is a viral disease, caused by the Equine Infectious Anemia virus (EIAV) belonging to the Retroviridae family, genus Lentivirus. Horses (or equids) infected with EIAV are lifelong carriers and they remain contagious for other horses even in the absence of clinical signs. So far, EIAV infection has been reported among horses in North and South America, France, Germany, Italy, Hungary and Romania, with no publication regarding the presence of EIAV in horses in Serbia. To determine the circulation of EIAV among, approximately, the 5000 horses of the Vojvodina region,...
Hébert L, Polledo G, Lecouturier F, Giorgi M, Beck C, Lowenski S, Laroucau K, Büscher P, Hans A, Becù T.Northern Argentina hosts equine populations living under preserved natural areas and extensive breeding conditions, with limited access to veterinary care. Horses can be in contact with i) wildlife considered to be a potential reservoir of horse pathogens (e.g. capybara, coatis and pampas deer) and/or ii) potential disease vectors such as ticks, horse flies, Culicidae and vampire bats. In this context, the aim of this study was to assess the exposure of horses from a herd in northern Argentina to different vector-borne pathogens. Serum samples were collected from 20 horses on a farm in Chaco p...
Romo-Sáenz CI, Tamez-Guerra P, Olivas-Holguin A, Ramos-Zayas Y, Obregón-Macías N, González-Ochoa G, Zavala-Díaz de la Serna FJ....Equine infectious anemia (EIA) is a highly infectious disease in members of the family, caused by equine infectious anemia virus (EIAV). The disease severity ranges from subclinical to acute or chronic, and causes significant economic losses in the equine industry worldwide. Serologic tests for detection of EIAV infection have some concerns given the prolonged seroconversion time. Therefore, molecular methods are needed to improve surveillance programs for this disease. We attempted detection of EIAV in 6 clinical and 42 non-clinical horses in Nuevo Leon State, Mexico, using the agar gel immu...
Machado G, Corbellini LG, Frias-De-Diego A, Dieh GN, Dos Santos DV, Jara M, de Freitas Costa E.Equine infectious anemia virus (EIAV) is a transboundary disease affecting a large number of equines worldwide. In this study, we assessed the transmission risk of EIAV in Rio Grande do Sul, Brazil. Serum samples from 1010 animals from 341 farms were initially analyzed using agar gel immunodiffusion to detect viral antibodies, and no antibody-positive animals were found. A risk assessment stochastic model was applied to generate the expected number of potential infections per month and to estimate the time to new infections. Our results estimated 6.5 months as the interval for new infections i...
Cursino AE, Lima MT, Nogueira MF, de Aguiar DM, Franco Luiz APM, Alves PA, Araujo Junior JP, Kroon EG.The aetiological agent of equine infectious anaemia (EIA) is the retrovirus equine infectious anemia virus (EIAV) that infects all members of the Equidae family. The EIA is widely disseminated in the Brazilian territory with a high seroprevalence in the Brazilian Pantanal and is mainly diagnosed using agar gel immunodiffusion (AGID). There are few complete EIAV genome sequences available in GenBank, which had an impact on molecular detection studies. In this study, we conducted molecular detection and sequencing of EIAV proviral DNA from Brazilian horses. We analysed the genomic region from ex...
Cappai MG, Pudda F, Wolf P, Accioni F, Boatto G, Pinna W.Wildlife protection and management are important priorities for landscape identity and biodiversity preservation. Feeding practices of fauna confined in facilities during temporary captivity are fundamental to support animal health and natural behavior. Appropriate provision of feedstuffs appears to be necessary to support the best practices in respect of animal species-specific natural diet. This investigation explored the variation of the metabolic profile by means of selected metabolite and respective circulating levels in a group feral Giara horses undergoing the change of the diet, moving...
Fagre AC, Mayo CE, Pabilonia KL, Landolt GA.Detection of is difficult as a result of intermittent leptospiruria and brief leptospiremia. Hence, diagnosis relies heavily on serologic testing, the reference method of which is the microscopic agglutination test (MAT). In horses, clinical leptospirosis has been associated with abortion, recurrent uveitis, and sporadic cases of hepatic and renal disease. Little information exists on the seroprevalence of antibodies to in equids in the United States; past nationwide studies suggest that the seroprevalence in some areas is as high as 77% (reciprocal titer ≥ 100). We tested sera from 124 ...
Lin Y, Wang XF, Wang Y, Du C, Ren H, Liu C, Zhu D, Chen J, Na L, Liu D, Yang Z, Wang X.Lentiviruses harbour high genetic variability for efficient evasion from host immunity. An attenuated equine infectious anaemia (EIA) vaccine was developed decades ago in China and presented remarkably robust protection against EIA. The vaccine was recently proven to have high genomic diversity, particular in . However, how and to what extent the high diversity relates to immune protection remains unclear. In this study, we compared immune protections and responses of three groups of horses stimulated by the high-diversity vaccine EIAV_HD, a single molecular clone of the vaccine EIAV_LD with ...
Bueno BL, Câmara RJF, Moreira MVL, Galinari GCF, Souto FM, Victor RM, Bicalho JM, Ecco R, Dos Reis JKP.Equine infectious anemia (EIA), a disease caused by equine infectious anemia virus (EIAV), is considered an obstacle to the development of the horse industry. There is no treatment or vaccine available for EIA, and its pathogenesis, as well as the immune response against the virus, is not fully understood. Therefore, an immunohistochemistry assay was developed for the detection of viral antigens in tissues of equids naturally infected with EIAV. Sections of organs of six equids from Apodi-RN, Brazil, that tested positive for EIA by serological tests (ELISA and AGID) were fixed in 10% formalin ...
Liu Q, Yu YY, Wang HY.Increasing evidence suggests that DNA methylation has key roles in the replication of retroviruses, including lentiviruses, and pathogenesis of diseases. However, the precise characteristics of CpG islands are not known for many retroviruses. In this study, we compared the distribution of CpG islands among strains of equine infectious anemia virus (EIAV), a lentivirus in the family Retroviridae and a model for HIV research. We identified CpG islands in 32 full-length EIAV genomic sequences obtained from the GenBank database using MethPrimer. Only one CpG island, from 100 to 120 bp, was identi...
Cook SJ, Li G, Zheng Y, Willand ZA, Issel CJ, Cook RF.Although the equine lentivirus (equine infectious anemia virus [EIAV]) poses a major threat to equid populations throughout most regions of the world, detailed knowledge concerning its molecular epidemiology is still in its infancy. Such information is important because the few studies conducted to date suggest there is extensive genetic variation between viral isolates that if confirmed has significant implications for future vaccine design and development of newer diagnostic procedures. Here, we avoid potential assembly artifacts inherent in composite sequencing techniques by using long-rang...
Zimmerli U, Thür B.Equine infectious anaemia (EIA) is a sporadic viral disease in many countries. Every single case has, however, a dramatic impact: infected animals have to be put down, and quarantine restrictions on horse movements lasting three months lead to substantial economic losses. In Switzerland, the mandatory notification was introduced in 1994 in order to facilitate international traffic. A year later, the "new" Ordinance on epizootics of 1995 classified EIA as a "disease to be eradicated". An infected polo horse in the canton of Argovia in summer 2017 thus represented Switzerland's first official ca...
Lohmann KL, James CR, Higgins SN, Howden KJ, Epp T.This retrospective study describes the detection of equine infectious anemia (EIA) during Canadian Food Inspection Agency (CFIA) disease investigations in Canada, examines aspects of importance for disease control, and evaluates potential animal-level risk factors for EIA in high-risk horses. Based on review of all EIA-positive samples and all samples collected during disease investigations (N = 4553) over a 4-year period (2009 to 2012), 409 EIA cases were detected. Horse owners with EIA cases owned between 1 and 60 affected animals, and 49 horses seroconverted during a disease investigation p...
Deshiere A, Berthet N, Lecouturier F, Gaudaire D, Hans A.Equine infectious anemia virus (EIAV) is responsible of acute disease episodes characterized by fever, anemia, thrombocytopenia and anorexia in equids. The high mutation rate in EIAV genome limited the number of full genome sequences availability. In the present study, we used the SureSelect target enrichment system with Illumina Next Generation Sequencing to characterize the proviral DNA of Equine Infectious Anemia Virus (EIAV) from asymptomatic horses. This approach allows a direct sequencing of the EIAV whole genome without cloning or amplification steps and we could obtain for the first ti...
Dorey-Robinson DLW, Locker N, Steinbach F, Choudhury B.Equine infectious anaemia virus (EIAV) is a retrovirus with worldwide distribution which is notifiable to the OIE. Despite its importance to the equine industry, most information regarding its biology have been obtained using only two strains (EIAV and EIAV ) from the USA and China, respectively. Recently full genome sequences from Ireland, Italy and Japan have been published; however, this is still not representative of the number of EIAV outbreaks experienced globally each year. The limited availability of published sequences makes design of a universal EIAV PCR difficult, hence diagnosis is...
Alnaeem AA, Hemida MG.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, especially in the Kingdom of Saudi Arabia (KSA). Objective: This study aimed to perform molecular and serol...
Seo MG, Kwon OD, Kwak D.A 23-year-old male Thoroughbred horse at the Korean Military Academy appeared thin with visible rib bones and presented clinical signs of fever, anorexia, lethargy, and severe dehydration. To determine the presence of various febrile disease-causing agents, the 23 cohabiting horses at the academy, including this horse, were subjected to hematology, blood chemistry, and molecular analysis using whole blood samples collected during regular medical check-ups. On the basis of clinical history, physical examination, hematology, blood chemistry, and fecal examination, differential diagnosis using mo...
Barros ML, Borges AMC, Oliveira De ACS, Lacerda W, O Souza De A, Aguiar DM.The prevalence of equine infectious anaemia (EIA) in the three biomes of the state of Mato Grosso (Amazon, Cerrado and Pantanal) was estimated. Serum samples were collected from 3,858 equines in 1,067 herds between Septemberand December 2014. The agar gel immunodiffusion (AGID) assay was used to detect EIA virus antibodies, and if a herd contained a seropositive animal itwas classified as a focus. The prevalence rates were 17.2% (95% confidence interval [CI]: 14.9-19.8%) for herds and 6.6% (95% CI: 5.8-7.5%) for animals. The Pantanal region showed the highest prevalence rates: 36.1% (95% CI: 3...
Equine infectious anaemia (EIA) is a disease with an almost worldwide distribution, with several outbreaks having been reported recently in European countries. In Italy, two regions, Lazio and Abruzzo, are considered as endemic areas for this disease. In nature, the EIA virus is mechanically transmitted by biting flies such as tabanids (Diptera: Tabanidae), although few studies have investigated the epidemiological implications. In the present study, several sites characterized by different levels of EIA prevalence were sampled. In sites with high tabanid populations, a seasonal succession of ...
Equine infectious anaemia (EIA) is a blood borne disease that is listed among the notifiable diseases of the World Organisation for Animal Health (OIE). EIA is also regulated by the OIE for the international trading provisions and is generally subject to control programmes. Since 2011, Italy has been conducting a surveillance plan based on a three-tier diagnostic system, using a serological ELISA as screening test, an agar gel immunodiffusion test (AGIDT) as a confirmatory method, and an immunoblot (IB) as an alternative confirmatory assay for discordant results between the first two tests. As...
Naves JHFF, Oliveira FG, Bicalho JM, Santos PS, Machado-de-Ávila RA, Chavez-Olortegui C, Leite RC, Reis JKP.Equine infectious anemia (EIA) is a disease caused by a Lentivirus that is currently controlled exclusively by identification of seropositive animals. In most countries, including Brazil, the official diagnostic test for EIA is the agar gel immunodiffusion test (AGID). Although this assay has a high specificity it can produce false negative reactions or equivocal results due to weak precipitation lines, especially in samples from donkeys, mules or newly infected equids. In this pioneering study, it was used overlapping synthetic peptide pools to map and identify a consensus, widely recognised ...
Cook RF, Barrandeguy M, Lee PA, Tsai CF, Shen YH, Tsai YL, Chang HG, Wang HT, Balasuriya UBR.Control of equine infectious anaemia (EIA) currently depends on serological diagnosis of infected equids. However, recently infected equids may not produce detectable anti-EIAV antibodies up to 157 days post infection and so present a high transmission risk. Therefore, direct nucleic acid detection methods are urgently needed to improve EIAV surveillance and management programs in counties where the disease is endemic. Objective: To evaluate a field-deployable, reverse transcription-insulated isothermal PCR (RT-iiPCR) assay targeting the conserved 5' untranslated region (5' UTR)/exon 1 of the ...
Meier K, Jaguva Vasudevan AA, Zhang Z, Bähr A, Kochs G, Häussinger D, Münk C.Human myxovirus resistance protein B (hMXB) is a restriction factor of HIV-1 that also inhibits a variety of retroviruses. However, hMXB is not antiviral against equine infectious anemia virus (EIAV). We show here that equine MX2 (eMX2) potently restricts EIAV in vitro. Additionally, eMX2 inhibits HIV-1 and other lentiviruses, including murine leukemia virus. Previously, it was reported that hMXB repression is reduced in hMXB Δ1-25, but not in GTP-binding mutant K131A and GTP-hydrolysis mutant T151A. In contrast to this phenomenon, our study indicates that eMX2 restriction is not diminished i...
Fontes KFLP, Silva-Júnior LC, Nascimento SA, Chaves DP, Pinheiro-Júnior JW, Freitas AC, Castro RS, Jesus ALS.A codon-optimized equine infectious anemia virus p26 gene was fused to a maltose-binding protein (MBP) and expressed in Escherichia coli for use as an antigen in agar gel immunodiffusion (AGID) and enzyme-linked immunosorbent assay (ELISA) for diagnosis of equine infectious anemia. An analysis of analytical sensitivity and specificity showed that the antigen MBP-p26rec reacted positively with a reference World Organization for Animal Health serum and demonstrated no cross-reaction against sera from vaccinated animals in either test. The diagnostic characteristics were evaluated and presented e...
Balaggan KS, Binley K, Esapa M, MacLaren RE, Iqball S, Duran Y, Pearson RA, Kan O, Barker SE, Smith AJ, Bainbridge JW, Naylor S, Ali RR.We evaluated the efficacy of equine infectious anaemia virus (EIAV)-based lentiviral vectors encoding endostatin (EIAV.endostatin) or angiostatin (EIAV.angiostatin) in inhibiting angiogenesis and vascular hyperpermeability in the laser-induced model of choroidal neovascularisation (CNV). Equine infectious anaemia virus.endostatin, EIAV.angiostatin or control (EIAV.null) vectors were administered into the subretinal space of C57Bl/6J mice. Two weeks after laser injury CNV areas and the degree of vascular hyperpermeability were measured by image analysis of in vivo fluorescein angiograms. Compar...
Ball JM, Rushlow KE, Issel CJ, Montelaro RC.We describe here a detailed analysis of the antigenic determinants of the surface unit glycoprotein (gp90) of equine infectious anemia virus (EIAV), using a comprehensive panel of synthetic peptides in enzyme-linked immunosorbent assays with immune serum from naturally and experimentally infected horses and with a panel of gp90-specific neutralizing and nonneutralizing monoclonal antibodies. The results of these studies identify immunoreactive segments throughout the conserved and variable domains of gp90 but localize immunodominant (100% reactivity) determinants to the amino and carboxyl term...
McGuire TC, Tumas DB, Byrne KM, Hines MT, Leib SR, Brassfield AL, O'Rourke KI, Perryman LE.Cytotoxic T lymphocytes (CTL) can control some viral infections and may be important in the control of lentiviruses, including human immunodeficiency virus type 1. Since there is limited evidence for an in vivo role of CTL in control of lentiviruses, dissection of immune mechanisms in animal lentiviral infections may provide needed information. Horses infected with equine infectious anemia virus (EIAV) a lentivirus, have acute plasma viremia which is terminated in immunocompetent horses. Viremic episodes may recur, but most horses ultimately control infection and become asymptomatic carriers. ...
Maury W.In vivo, equine infectious anemia virus (EIAV) replicates in tissues rich in macrophages, and it is widely believed that the tissue macrophage is the principal, if not sole, cell within the host that replicates virus. No viral replication has been detected in circulating peripheral blood monocytes. However, proviral DNA can be detected in these cells, and monocytes may serve as a reservoir for the virus. In this study, an in vitro model was developed to clarify the role of monocyte maturation in regulating EIAV expression. Freshly isolated, nonadherent equine peripheral blood monocytes were in...
Carpenter S, Evans LH, Sevoian M, Chesebro B.Equine infectious anemia virus was isolated from peripheral blood leukocytes collected during two early febrile cycles of an experimentally infected horse. RNase T1-resistant oligonucleotide fingerprint analyses indicated that the nucleotide sequences of the isolates differed by approximately 0.25% and that the differences appeared randomly distributed throughout the genome. Serum collected in the interval between virus isolations was able to distinguish the isolates by membrane immunofluorescence on live cells. However, no neutralizing antibody was detected in the interval between virus isola...
Derse D, Dorn PL, Levy L, Stephens RM, Rice NR, Casey JW.The long terminal repeats (LTRs) of equine infectious anemia virus (EIAV) were examined with respect to their ability to function as transcriptional promoters in various cellular environments. Nucleotide sequence analyses of the LTRs derived from two unique proviral clones revealed the requisite consensus transcription and processing signals. One of the proviruses possessed a duplication of a 16-base-pair sequence in the CCAAT box region of the LTR which was absent in the other provirus. To assess its functional activity, each LTR was coupled to the bacterial chloramphenicol acetyltransferase ...
Hammond SA, Li F, McKeon BM, Cook SJ, Issel CJ, Montelaro RC.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 long-term inapparent carriage. We previously described the evolution of EIAV genomic quasispecies (C...
Dorn PL, Derse D.Deletion analysis of the equine infectious anemia virus long terminal repeat revealed that sequences responsive to virus-specific transactivation are located within the region spanning the transcriptional start site (-31 to +22). In addition, an active exon of a trans-acting factor (tat) was identified downstream of pol and overlapping env (nucleotides 5264 to 5461). Activation by tat is accompanied by an increase in the steady-state levels of mRNA directed by the equine infectious anemia virus long terminal repeat.
Yin X, Hu Z, Gu Q, Wu X, Zheng YH, Wei P, Wang X.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 tool for understanding its antiviral mechanism. Here, we report cloning of equine tetherin and charact...
Charman HP, Bladen S, Gilden RV, Coggins L.Equine infectious anemia virus (EIAV) has a density of 1.154 g/cm3 in sucrose a high-molecular-weight RNA similar in size to Rauscher murine leukemia virus, and an internal virion reverse transcriptase that utilizes the synthetic RNA template poly(rA) but not the synthetic DNA template poly(dA), both with (dT)12 as primer. Although capable of utilizing manganese at low concentrations (approximately 0.1 mM), EIAV reverse transcriptase showed highest activity in the presence of 9 mM magnesium. The major protein of EIAV has a slightly lower molecular weight than the comparable protein of type C v...
Binley K, Widdowson PS, Kelleher M, de Belin J, Loader J, Ferrige G, Carlucci M, Esapa M, Chipchase D, Angell-Manning D, Ellis S, Mitrophanous K....RetinoStat(®) is an equine infectious anemia virus-based lentiviral gene therapy vector that expresses the angiostatic proteins endostatin and angiostatin that is delivered via a subretinal injection for the treatment of the wet form of age-related macular degeneration. We initiated 6-month safety and biodistribution studies in two species; rhesus macaques and Dutch belted rabbits. After subretinal administration of RetinoStat the level of human endostatin and angiostatin proteins in the vitreous of treated rabbit eyes peaked at ∼1 month after dosing and remained elevated for the duration o...
Zhang B, Jin S, Jin J, Li F, Montelaro RC.Characterization of cellular receptors for human, simian, and feline immunodeficiency viruses that are tropic for lymphocytes and macrophages have revealed a common theme of a sequential binding of viral envelope proteins with two coreceptors to mediate virus infection of target cells. In contrast to these dual tropic immunodeficiency viruses, the ungulate lentiviruses, including equine infectious anemia virus (EIAV), exclusively infect cells of the monocyte-macrophage lineage to cause progressive degenerative diseases without clinical immunodeficiency. EIAV causes a uniquely dynamic disease t...
Wang SZ, Rushlow KE, Issel CJ, Cook RF, Cook SJ, Raabe ML, Chong YH, Costa L, Montelaro RC.The potential for antibody-dependent enhancement of replication of macrophage/monocyte tropic viruses has posed a significant problem in the development of vaccines for several animal and human viruses and has raised significant concern in the design of potential AIDS vaccines. Using the previously described equine infectious anemia virus/Shetland pony system as a model for HIV-1 vaccine development, we have evaluated the efficacy of a recombinant subunit vaccine containing a baculovirus-expressed envelope surface glycoprotein (gp90) of EIAV. The results of these trials demonstrate not only th...
Leroux C, Craigo JK, Issel CJ, Montelaro RC.A primary mechanism of lentivirus persistence is the ability of these viruses to evolve in response to biological and immunological selective pressures with a remarkable array of genetic and antigenic variations that constitute a perpetual natural experiment in genetic engineering. A widely accepted paradigm of lentivirus evolution is that the rate of genetic variation is correlated directly with the levels of virus replication: the greater the viral replication, the more opportunities that exist for genetic modifications and selection of viral variants. To test this hypothesis directly, we ex...
Zielonka J, Bravo IG, Marino D, Conrad E, Perković M, Battenberg M, Cichutek K, Münk C.The mammalian APOBEC3 (A3) proteins comprise a multigene family of cytidine deaminases that act as potent inhibitors of retroviruses and retrotransposons. The A3 locus on the chromosome 28 of the horse genome contains multiple A3 genes: two copies of A3Z1, five copies of A3Z2, and a single copy of A3Z3, indicating a complex evolution of multiple gene duplications. We have cloned and analyzed for expression the different equine A3 genes and examined as well the subcellular distribution of the corresponding proteins. Additionally, we have tested the functional antiretroviral activity of the equi...
Cook RF, Leroux C, Cook SJ, Berger SL, Lichtenstein DL, Ghabrial NN, Montelaro RC, Issel CJ.An 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 gene (including the first exon of rev), and the 3' long terminal repeat (LTR). Modified 19-2-6A mol...
Belshan M, Baccam P, Oaks JL, Sponseller BA, Murphy SC, Cornette J, Carpenter S.Genetic and biological variation in the regulatory protein Rev of equine infectious anemia virus (EIAV) were examined throughout a clinically dynamic disease course of an experimentally infected pony. Following infection with the virulent EIAV(Wyo), the pony underwent a variable disease course, including an acute fever episode at 12 days postinfection (DPI), multiple recurrent fever episodes until 135 DPI, a prolonged subclinical period, and two late fever episodes. Viral RNA was isolated from the inoculum and sequential sera samples, and the rev exon 2/gp45 overlapping ORFs were amplified, cl...
Rice NR, Lequarre AS, Casey JW, Lahn S, Stephens RM, Edwards J.The amount and distribution of viral DNA were established in a horse acutely infected with the Wyoming strain of equine infectious anemia virus (EIAV). The highest concentration of viral DNA were found in the liver, lymph nodes, bone marrow, and spleen. The kidney, choroid plexus, and peripheral blood leukocytes also contained viral DNA, but at a lower level. It is estimated that at day 16 postinoculation, almost all of the viral DNA was located in the tissues, with the liver alone containing about 90 times more EIAV DNA than the peripheral blood leukocytes did. Assuming a monocyte-macrophage ...
Carpenter S, Chesebro B.Similar to other human and animal lentiviruses, equine infectious anemia virus (EIAV) is detectable in vivo in cells of the monocyte-macrophage lineage. Owing to their short-lived nature, horse peripheral blood macrophage cultures (HMC) are rarely used for in vitro propagation of EIAV, and equine dermal (ED) or kidney cell cultures, which can be repeatedly passed in vitro, are used in most studies. However, wild-type isolates of EIAV will not grow in these cell types without extensive adaptation, a process which may attenuate viral virulence. To better define the effect of host cell tropism on...
Belshan M, Harris ME, Shoemaker AE, Hope TJ, Carpenter S.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 be an important mechanism for regulation of virus replication in vivo and may contribute to changes ...
Barnard BJ.Twenty-four species of South African wild animals were tested for the presence of antibodies against the viruses of 16 common diseases of domestic animals. Positive results were obtained for African horsesickness, equine encephalosis, equid herpes virus-1, infectious bovine rhinotracheitis, Allerton disease (Herpes mammillitis), lumpy skin disease, parainfluenza, encephalomyocarditis, bluetongue, Wesselsbron disease, bovine ephemeral fever, and Akabane disease complex. No antibodies could be demonstrated against the viruses of equine influenza, equine infectious anaemia, equine viral arteritis...
Payne SL, Salinovich O, Nauman SM, Issel CJ, Montelaro RC.Comparisons of peptide and oligonucleotide maps of glycoproteins and RNA from nine isolates of equine infectious anemia virus (EIAV) that were generated during parallel infections of two Shetland ponies revealed that each isolate was structurally unique. Each EIAV isolate contained a unique subset of variant peptides, oligonucleotides, or both, indicating that structural variation in EIAV is a random and noncumulative process and that a large spectrum of possible EIAV variants can be generated in infected animals.
Orrego A, Issel CJ, Montelaro RC, Adams WV.Five serial passages of a cell-adapted strain of equine infectious anemia (EIA) virus were conducted in Shetland ponies. The 13 recipient ponies became agar-gel immunodiffusion test-positive by 25 days after they were inoculated. The virulence of the cell-adapted strain of EIA virus markedly increased through 3 serial passages, although individual variation within passages was high. The 1st serial-passage recipient remained afebrile through 200 days, whereas a febrile episode occurred about every 185, 44, 35, and 33 days in the 2nd, 3rd, 4th, and 5th serial-passage recipients, respectively. Se...
Derse D, Carvalho M, Carroll R, Peterlin BM.Transcriptional regulatory mechanisms found in lentiviruses employ RNA enhancer elements called trans-activation responsive (TAR) elements. These nascent RNA stem-loops are cis-acting targets of virally encoded Tat effectors. Interactions between Tat and TAR increase the processivity of transcription complexes and lead to efficient copying of viral genomes. To study essential elements of this trans activation, peptide motifs from Tats of two distantly related lentiviruses, equine infectious anemia virus (EIAV) and human immunodeficiency virus type 1 (HIV-1), were fused to the coat protein of b...
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...
Borroto-Esoda K, Boone LR.The endogenous reverse transcriptase reaction of equine infectious anemia virus (EIAV) has been studied, and conditions allowing synthesis of full-length minus-strand DNA have been determined. In contrast to results reported for other retroviruses, synthesis of EIAV full-length minus-strand DNA was not impaired by high concentrations of Nonidet P-40, a nonionic detergent used to make the virion envelope permeable. All components of the reaction were titrated for maximum synthesis of complete minus strands, and a time course under the standardized conditions was determined. Minor subgenomic ban...
