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.
Acevedo-Jiménez GE, Morales-González C, Akbarin MM, Rodríguez-Murillo C, González-Fernández VD, Avila-De la Vega LM, García-Flores MM....Equine infectious anemia virus (EIAV) is a globally significant equine pathogen, and its control relies on effective serological surveillance. The agar gel immunodiffusion (AGID) test, the WOAH-prescribed method, has limitations in sensitivity. This study developed and validated an indirect ELISA using a synthetic peptide derived from a conserved region of the EIAV gp90 surface glycoprotein. The assay was evaluated using 773 horse sera from the Metropolitan Zone of the Valley of Mexico and compared to the AGID test. The gp90-EIAV ELISA demonstrated a sensitivity of 85.3 % and a specificity o...
Gordon S, Pusterla N, Finno CJ, Young A, Martínez-López B.Equine alphaherpesvirus-1 (EHV-1) is a highly contagious virus that can cause the neurological form, equine herpesvirus myeloencephalopathy (EHM). Understanding transmission-related risk factors is crucial for improving prevention strategies and guiding effective control measures. In this study, we collected data from 63 horses that had previously participated in the February 2022 winter horse show season at the Desert International Horse Park (DIHP) (26 cases and 37 controls) to identify host and management factors associated with EHV-1 infection and/or EHM development during the February 202...
Garzaro D, Rodríguez N, Medina G, Alcazar W, Gualdron M, Siem JA, Sulbaran Y, Barrios M, Liprandi F, Jaspe RC, Pujol FH.Madariaga virus (MADV), formerly known as the South American variant of Eastern Equine Encephalitis virus (EEEV), is an alphavirus that belongs to the family and has been periodically infecting equids in Venezuela since its first identification in 1975. This study reports the isolation and molecular characterization of MADV isolated from a horse in December 2024 in the context of MADV cases reported in Venezuela. Methods: Antibodies to the rabies virus were detected by indirect immunofluorescence, and to the Equine Infectious Anemia virus (EIAV) by passive immunodiffusion. MADV RNA was detect...
In 2017, Spain reported its first equine infectious anemia virus (EIAV) outbreak in 34 years, affecting three horses in two unrelated holdings in Candeleda (Ávila) and Serradilla (Cáceres), with no apparent epidemiological link between premises. Phylogenetic analysis of whole genome and the gene revealed that the Spanish EIAV strains form a distinct monophyletic clade, sharing more than 99% nucleotide identity, suggesting a common contamination event. Interestingly, these three viral strains seem to cluster with North American strains, sharing up to 80.12% nucleotide identity, notably with ...
Gonzálvez M, Franco JJ, Cano-Terriza D, Barbero-Moyano J, Jose-Cunilleras E, García J, Alguacil E, García-Bocanegra I.Equine Infectious Anemia (EIA) is a notifiable disease caused by Equine Infectious Anemia Virus (EIAV), with major sanitary and economic importance for equids worldwide. There is limited and outdated information on the circulation of EIAV in many European countries. In the present study, we aimed to assess virus exposure in different equid species in Western Europe. Methods: Between 2011 and 2023, a cross-sectional study was conducted to investigate the seroprevalence of EIAV in 1676 equids (1444 horses, 106 donkeys and 126 mules/hinnies) from four European regions: Andalusia (Southern Spain; ...
Costa VMD, de Aguiar Filho RN, Braz GF, Paz CFR, Drumond BP, Teixeira BM, Kroon EG.Equine infectious anemia (EIA) is a chronic disease caused by the equine infectious anemia virus (EIAV), a member of the Retroviridae family and the Lentivirus genus. Most infected animals are asymptomatic carriers, which makes clinical diagnosis challenging. This study aimed to conduct a clinical and laboratory evaluation of EIA in equids used for equestrian tourism in Jericoacoara National Park, Ceará, Brazil. A total of 112 equids (104 horses and 8 mules) underwent clinical, hematological, biochemical, serological, and molecular assessments. The EIAV seropositivity rates were 11.6% by AGID...
Krücken J, Diekmann I, Andreotti S, Bredtmann CM, Mbedi S, Sparmann S, Schmidt JS, de Almeida Borges F, de Freitas MG, Sallé G, Hofer H....Equines are parasitized by complex communities of Strongylidae (Nematoda) comprising multi-species infections. Currently, Cyathostominae are most prevalent, while Strongylus species are only rarely detected. Since eggs and, in most cases, infective larvae cannot be differentiated to species level, except for Strongylus spp., species-specific knowledge of the pathology, epidemiology and ecology of these parasitic nematodes is limited. Reference sequence data for several cyathostomin species are limited or missing. Deep amplicon sequencing of internal transcribed spacer 2 (ITS-2) regions of nema...
Equestrian sports play a significant economic role in the horse industry. In recent years, numerous equine viruses have emerged, among which are equine Pegiviruses and the re-emerging Equine coronavirus (ECoV). These viruses are distributed globally and primarily cause subclinical infections with unknown morbidity, even if ECoV can occasionally induce febrile and diarrheic episodes. To broaden the data on the Italian equine population, a study was conducted to assess their prevalence in two distinct horse populations belonging to the Carabinieri Corps (CC) and the Italian Army (IA) of the Ital...
Andreas C.The virus that causes African horsesickness does not affect any indigenous species, but produces high mortality among horses, a species introduced by the Dutch East India Company in 1653. While the insect-borne disease did not occur in the immediate vicinity of the Cape Peninsula, horsesickness could have constituted an endemic disease barrier to the horse-based expansion of the colonial sphere into the hinterland, where it was seasonally prevalent. That it did so to only a limited extent is due to a substantial alteration of the ecology of the disease that largely resulted from inadvertent si...
Wang J, Qiu J, Wang M, Wu X, Li X, Zhang H.Equine infectious anemia virus (EIAV) poses a significant global threat to the equine industry, resulting in considerable economic losses and compromised horse health. Given the limited treatment options available, early detection and prevention strategies are essential to combat this viral infection. In this study, we introduce a novel colloidal gold immunochromatographic (ICLF) strip for the rapid and accurate detection of EIAV antibodies. The strip incorporates a unique fusion protein, p26-gp90, designed to enhance both the specificity and sensitivity of the detection method for EIAV antibo...
Ostuni A, Frontoso R, Crudele MA, Barca L, Amati M, Boni R, De Vendel J, Raimondi P, Bavoso A.Equine Infectious Anemia Virus (EIAV), a lentivirus marked by considerable genetic variability, poses significant diagnostic challenges. Existing diagnostic tools encompass the Agar Gel Immunodiffusion Assay (AGID), enzyme-linked immunosorbent assay (ELISA), and Western blotting (WB). ELISA and AGID mainly utilize the p26 capsid protein, often sourced from the Wyoming reference strain. To broaden the range of viral proteins and strains employed in these immunoassays, we previously developed a novel p26/double-strain gp45 indirect ELISA. In this study, we evaluated the performance of this ELISA...
Firdausy LW, Fikri F, Wicaksono AP, Çalışkan H, Purnama MTE.Equine infectious anemia (EIA) is a lentiviral disease affecting members of the Equidae family, with global distribution and significant implications for animal health and biosecurity. Despite numerous individual reports, a comprehensive synthesis of its global prevalence and risk factors remains lacking. This study aimed to conduct a systematic review and meta-analysis to estimate the global prevalence of EIA, identify diagnostic trends, and evaluate factors associated with heterogeneity across studies. Unassigned: A systematic search was conducted in six major databases (PubMed, Scopus, Web ...
Thieulent CJ, Carossino M, Reis JKPD, Vissani MA, Barrandeguy ME, Valle-Casuso JC, Balasuriya UBR.Equine Infectious Anemia Virus (EIAV), the causative agent of Equine Infectious Anemia (EIA), presents a significant threat to equine populations worldwide. While local EIAV prevalence has been estimated in several studies, no global prevalence has been determined. Thus, this study aimed to review the literature on EIAV prevalence in the 21st century. A comprehensive electronic search was conducted in PubMed, Web of Science, Scopus, Google Scholar, SciELO.org, African Journals Online, and NZresearch.org, yielding 105 articles published between January 1st, 2000, and December 31st, 2024 (spanni...
Pinho APVB, Ferreira F, Fuck JJ, de Oliveira JP, Dias RA, Grisi-Filho JHH, Heinemann MB, Telles EO, Amaku M, Ferreira Neto JS.Considering that control strategies for Equine Infectious Anemia, based on the serological diagnosis of equids and the removal of positive animals, may not be optimal for developing countries with an absolute predominance of grade working animals, this study aimed to address this issue based on the epidemiological situation of the disease in Pará, a state in the Brazilian Amazon. Pará was divided into five regions, and within each region a pre-established number of farms were randomly selected. Within each farm, a pre-set number of animals were randomly selected and submitted to Agar Gel Imm...
James K, Chappell DE, Craig B, Pariseau C, Wright C, van Harreveld P, Barnum S, Pusterla N.The purpose of this study was to determine any associations of EHV-2, EHV-5, and dual infection with EHV-2/-5 with demographic parameters, clinical signs, and coinfection with other common respiratory pathogens. Nasal swabs collected from 9737 horses were tested for EHV-2 and EHV-5, as well as EHV-1, EHV-4, EIV, , ERAV, and ERBV, by qPCR. Clinical signs and demographic parameters were recorded, and prevalence factors were evaluated for significance regarding EHV-2 and/or EHV-5 infection. Out of the 9737 horses in this study, 17.8% tested EHV-2-positive ( = 1731), 15.8% tested EHV-5-positive ( ...
Domínguez-Odio A, González LIC, Alfonso DM, Guevara-Hernández F, La O Arias MA, Zayas MP, Ríos MÁB.The transmembrane glycoprotein gp45 (implicated in virus-equine B lymphocyte binding and in subsequent infection) is an important protein used as an antigen in the serological diagnosis of equine infectious anemia, but synthetic peptides derived from its structure are not. Consequently, the present study aimed to determine the diagnostic performance of the Bio-AIELAB immunoassay (novel synthetic peptide P05/gp45) in comparison with a similar commercial assay (ELISA EIA, VMRD Inc, USA) and with the gold standard (AGID, LABIOFAM, Cuba). A total of 365 samples of sera from naturally infected Cuba...
da Silva VV, de Sá Barreto Maia Leite DP, de Crasto Souza Carvalho Reis J, de Almeida Braz BM, Junior JWP, de Almeida JC, Mota RA.This study identifies high-risk areas for Equine Infectious Anemia (EIA) in Brazil and analyzes the temporal trend of the disease across regions and Federative Units over an 18-year period (2006-2023), using data from the National Animal Health Information System (SIZ). During the analyzed period, 111,826 cases of EIA were reported in Brazil, with a predominance in the Northeast (39.75 %), Central-West (27.56 %), and North (20.95 %) regions. The state of Mato Grosso recorded the highest number of cases (17.02 %), while Sergipe had the lowest (0.36 %). In the incidence risk analysis, the s...
Peris MP, Serrano M, Romero A, García M, Halaihel N, Castillo JA, Gracia MJ.Equine piroplasmosis (EP), a tick-borne disease caused by Babesia caballi and Theileria equi, is of significant concern due to its impact on the international horse trade. According to standards established by the World Organisation for Animal Health (WOAH), horses imported from EP-endemic regions must have a certificate confirming negative serological and molecular test results. In EP-free countries, only seronegative horses are allowed to enter. This entails economic losses for endemic regions such as Spain. Our study aimed to assess the prevalence of B. caballi and T. equi in horses from no...
Nadal C, Chanet C, Delaunay C, Pitel PH, Marsot M, Bonnet SI.Equine piroplasmosis, caused by the protozoan parasites Babesia caballi and Theileria equi, is endemic in Europe's Mediterranean basin, creating significant health and economic challenges for the equine sector. With no available vaccine, an eco-epidemiological approach is essential in order to identify and implement effective preventive measures. With this aim in view, we identified risk factors associated with B. caballi and T. equi infections and tick infestation for draught horses in the Auvergne-Rhône-Alpes region of France, known for its high piroplasmosis seroprevalence. During the spri...
Blomström AL, Källse A, Riihimäki M.Viral infections pose a significant challenge to the equine population, compromising welfare and causing substantial economic losses for the global equine industry. While numerous equine viral pathogens have been identified, many suspected viral infections remain undiagnosed. This highlights the need for further identification and characterization of viruses circulating within the equine population. In this study, we utilized viral metagenomics to investigate viruses present in serum samples and nasal swabs collected from horses in Sweden. The primary focus was on horses presenting with fever,...
Equine infectious anemia virus (EIAV) is the simplest described within the family, related to the human immunodeficiency viruses (HIV-1 and HIV-2). There is an important interplay between host cells and viruses. Viruses need to hijack cellular proteins for their viral cycle completion and some cellular proteins are antiviral agents interfering with viral replication. HIV cellular partners have been extensively studied and described, with a special attention to host proteins able to inhibit specific steps of the viral cycle, called restriction factors. Viruses develop countermeasures against ...
Equine infectious anemia virus (EIAV) is an equine lentivirus related to human immunodeficiency virus type 1 (HIV-1). Both viruses are related among the Retroviridae family, but their clinical manifestations are different as EIAV causes a long persistent infection with no progressive immune dysfunction in most cases. Today, no treatment is approved against EIAV, contrary to HIV-1, manageable through antiretroviral therapy, known as HAART (highly active antiretroviral therapy) or cART (combination antiretroviral therapy). No information about the efficacy of antiretroviral drugs against EIAV is...
Padalino B, Pellegrini F, Felici M, Zappaterra M, Catella C, Cordisco M, Lorusso E, Cirone F, Pratelli A.Respiratory disorders (RDs) are a common transport-related welfare consequence in horses. This prospective study described the journeys of horses transported to two slaughterhouses in Italy, documented the prevalence of potentially RD-related pathogens, and identified possible predisposing factors. Data were recorded from arrival until 48 h after arrival and included the collection of Deep Nasopharyngeal Swabs (DNS), journey details and welfare assessment of horses (n = 155). PCR was used to quantify the presence of influenza A virus, reovirus, equine herpesvirus type 1 and 4, adenovirus, r...
Cardeti G, Manna G, Cersini A, Nardini R, Rosati S, Reina R, Cittadini M, Sittinieri S, Altigeri A, Marcario GA, Scicluna MT.The mechanisms of the innate immunity control of equine infectious anemia virus in horses are not yet widely described. Equine monocytes isolated from the peripheral blood of three Equine infectious anemia (EIA) seronegative horses were differentiated in vitro into macrophages that gave rise to mixed cell populations morphologically referable to M1 and M2 phenotypes. The addition of two equine recombinant cytokines and two EIA virus reference strains, Miami and Wyoming, induced a more specific cell differentiation, and as for other species, IFNγ and IL4 stimulation polarized horse macrophages...
Nishimura F, Fukushi N, Sakai H, Fukushi H.Equine herpesvirus type 1 (EHV-1) causes abortion, respiratory infection, and neurological diseases (equine herpesvirus myeloencephalopathy) in horses. A single nucleotide polymorphism (SNP) associated with a single amino acid in the DNA polymerase gene (ORF30, in which D752 is neuropathogenic and N752 is non-neuropathogenic) of EHV-1 has been associated with neuropathogenicity in horses. We constructed an EHV-1 Ab4p ORF30 N752 mutant and a repair virus to examine the effect of a D752N mutation on the neuropathogenicity of the virus in Syrian hamsters. The N752 mutation did not affect viral gr...
Haywood LMB, Sheahan BJ.Equine colitis is a devastating disease with a high mortality rate. Infectious pathogens associated with colitis in the adult horse include Clostridioides difficile, Clostridium perfringens, Salmonella spp., Neorickettsia risticii/findlaynesis, and equine coronavirus. Antimicrobial-associated colitis can be associated with the presence of infectious pathogens. Colitis can also be due to non-infectious causes, including non-steroidal anti-inflammatory drug administration, sand ingestion, and infiltrative bowel disease. Current treatments focus on symptomatic treatment (restoring fluid and elect...
An Q, Li Y, Sun Z, Gao X, Wang H.Equine Infectious Anemia (EIA) is a vector-borne persistent viral infection in equine animals. The EIA is characterized by recurrent fever, thrombocytopenia, depression, anemia, rapid weight loss, and lower body edema. Control of EIA is achieved through the elimination or isolation of infected animals, resulting in significant economic losses. In recent years, many countries in Europe have experienced outbreaks of EIA, which could potentially develop into a new wave of epidemic and pose a significant threat to the healthy development of the equine industry. This study utilized spatiotemporal a...
Schumacher A, Gehlen H.This literature review analyzes the historical development of polo, its organizational structure, the course of the game, as well as the breeding, rearing, and training practices of polo horses. Frequently occurring ailments, such as musculoskeletal injuries, respiratory diseases, and internal illnesses, are highlighted. Lameness is a major problem, with injuries to the superficial digital flexor tendon being the most common cause. Other notable diseases include exercise-induced pulmonary hemorrhage (EIPH), myositis, rhabdomyolysis, and equine infectious anemia (EIA). To ensure the welfare of ...
Carvelli A, Nardini R, Carnio A, Ricci I, Rosone F, Sala M, Simeoni S, Maccarone D, Scicluna MT.Equine infectious anaemia (EIA) is a life-long viral infection affecting equids, transmitted mechanically by biting flies and iatrogenic means. Despite its global distribution, active surveillance is limited, with passive clinical surveillance or control of specific equine sectors prevailing. In Italy, a national surveillance plan in horse, donkey, and mule populations has been established and includes mandatory passive and active surveillance through annual serological tests. During 2007-2010, the agar gel immunodiffusion (AGID) test served as both screening and confirmatory tests. Since 2011...
Linnegar B, Kerlin DH, Eby P, Kemsley P, McCallum H, Peel AJ.To identify the size and distribution of the horse population in the Northern Rivers Region of NSW, including changes from 2007 to 2021, to better understand populations at risk of Hendra virus transmission. Methods: Census data from the 2007 Equine Influenza (EI) outbreak were compared with data collected annually by New South Wales Local Land Services (LLS) (2011-2021), and with field observations via road line transects (2021). Results: The horse populations reported to LLS in 2011 (3000 horses; 0.77 horses/km) was 145% larger than that reported during the EI outbreak in 2007 (1225 horses; ...
Puffer BA, Parent LJ, Wills JW, Montelaro RC.We have previously demonstrated that the Gag p9 protein of equine infectious anemia virus (EIAV) is functionally homologous with Rous sarcoma virus (RSV) p2b and human immunodeficiency virus type 1 (HIV-1) p6 in providing a critical late assembly function in RSV Gag-mediated budding from transfected COS-1 cells (L. J. Parent et al., J. Virol. 69:5455-5460, 1995). In light of the absence of amino acid sequence homology between EIAV p9 and the functional homologs of RSV and HIV-1, we have now designed an EIAV Gag-mediated budding assay to define the late assembly (L) domain peptide sequences con...
Montelaro RC, Parekh B, Orrego A, Issel CJ.The recurrent nature of equine infectious anemia has been attributed to relatively rapid antigenic variations in equine infectious anemia virus (EIAV) during persistent infection under selective immune pressures. This model was tested by serological and biochemical analysis of virus isolates recovered from separate febrile episodes in two experimentally infected ponies. Neutralization assays employing immune sera from the experimentally infected ponies demonstrated that distinct antigenic strains of virus predominate during sequential febrile episodes in a single pony. Analysis of the test str...
Schneider J, Kaaden O, Copeland TD, Oroszlan S, Hunsmann G.Two glycopolypeptides with molecular weights 160,000 and 120,000 (gp120) are regularly recognized by human immunodeficiency virus (HIV)-specific antisera in lysates of cells persistently infected with HIV. In the present study, gp120 was characterized as the major envelope glycopolypeptide of HIV. Gp120 was identified as the external viral glycoprotein by radiosequencing and by its presence in purified virus. However gp120 was predominantly shed as a soluble protein into the culture fluid. Furthermore gp120 was precipitated by sera from horses infected with equine infectious anaemia virus (EIA...
Leroux C, Cadoré JL, Montelaro RC.Equine Infectious Anemia Virus (EIAV) is a lentivirus, of the Retrovirus family, with an almost worldwide distribution, infecting equids. It causes a persistent infection characterized by recurring febrile episodes associating viremia, fever, thrombocytopenia, and wasting symptoms. The disease is experimentally reproducible by inoculation of Shetland ponies or horses with EIAV pathogenic strains. Among lentiviruses, EIAV is unique in that, despite a rapid virus replication and antigenic variation, most animals progress from a chronic stage characterized by recurring peaks of viremia and fever ...
Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC.Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been...
Puffer BA, Watkins SC, Montelaro RC.We have identified an interaction between the equine infectious anemia virus (EIAV) late assembly domain and the cellular AP-2 clathrin-associated adapter protein complex. A YXXL motif within the EIAV Gag late assembly domain was previously characterized as a sequence critical for release of assembling virions. We now show that this YXXL sequence interacts in vitro with the AP-50 subunit of the AP-2 complex, while the functionally interchangeable late assembly domains carried by the Rous sarcoma virus p2b protein and human immunodeficiency virus type 1 p6 protein, which utilize PPPY and PTAPP ...
Salinovich O, Payne SL, Montelaro RC, Hussain KA, Issel CJ, Schnorr KL.Previous results from our laboratory have demonstrated that equine infectious anemia virus displays structural variations in its surface glycoproteins and RNA genome during passage and chronic infections in experimentally infected Shetland ponies (Montelaro et al., J. Biol. Chem. 259:10539-10544, 1984; Payne et al., J. Gen. Virol. 65:1395-1399, 1984). The present study was undertaken to obtain an antigenic and biochemical characterization of equine infectious anemia virus isolates recovered from an experimentally infected pony during sequential disease episodes, each separated by intervals of ...
Cheevers WP, McGuire TC.Equine infectious anemia (EIA) is a chronic, relapsing infectious disease of horses caused by a nononcogenic retrovirus. Virus persists in infected animals for life and can be reliably detected by serologic tests that measure levels of antibody to the major structural protein of the virus. Periodic virus replication in macrophages leads to an immunologically mediated acute disease characterized primarily by severe anemia. Recrudescence of acute EIA is the result of antigenic variation of the surface glycoprotein of EIA virus. The frequency and severity of clinical episodes of EIA decrease in m...
Rushlow K, Olsen K, Stiegler G, Payne SL, Montelaro RC, Issel CJ.The nucleotide sequence of the envelope (env) gene region of equine infectious anemia virus (EIAV), a member of the lentivirus subfamily of retroviruses, has been determined from a clone of integrated proviral DNA for which the gag and pol sequences have been reported previously. The env gene is 859 codons in length and the sequence reported here is consistent with the published biochemical properties of EIAV glycoproteins. The env gene region of EIAV shares considerable structural similarities but negligible sequence homologies with the env genes of other members of the lentivirus subfamily, ...
Leroux C, Issel CJ, Montelaro RC.We have investigated the genetic evolution of three functionally distinct regions of the equine infectious anemia virus (EIAV) genome (env, rev, and long terminal repeat) during recurring febrile episodes in a pony experimentally infected with a well-characterized reference biological clone designated EIAV(PV). Viral populations present in the plasma of an EIAV(PV)-infected pony during sequential febrile episodes (18, 34, 80, 106, and 337 days postinfection) were amplified from viral RNA, analyzed, and compared to the inoculated strain. The comparison of the viral quasispecies showed that the ...
Shehu-Xhilaga M, Ablan S, Demirov DG, Chen C, Montelaro RC, Freed EO.The Gag proteins of a number of different retroviruses contain late or L domains that promote the release of virions from the plasma membrane. Three types of L domains have been identified to date: Pro-Thr-Ala-Pro (PTAP), Pro-Pro-X-Tyr, and Tyr-Pro-Asp-Leu. It has previously been demonstrated that overexpression of the N-terminal, E2-like domain of the endosomal sorting factor TSG101 (TSG-5') inhibits human immunodeficiency virus type 1 (HIV-1) release but does not affect the release of the PPPY-containing retrovirus murine leukemia virus (MLV), whereas overexpression of the C-terminal portion...
Payne SL, Fang FD, Liu CP, Dhruva BR, Rwambo P, Issel CJ, Montelaro RC.The extent and nature of genomic variation among nine antigenically distinct EIAV isolates recovered during sequential clinical episodes from two experimentally infected ponies were examined by restriction fragment analysis and nucleotide sequencing. Only minor variations in restriction enzyme patterns were observed among the viral genomes. In contrast, env gene sequences of four isolates from one pony revealed numerous clustered base substitutions. Divergence in env gene nucleotide and deduced amino acid sequences between pairs of virus isolates ranged from 0.62 to 3.4% env gene mutation rate...
Sellon DC, Perry ST, Coggins L, Fuller FJ.In situ hybridization of tissues from two horses infected with the wild-type Wyoming strain of equine infectious anemia virus (EIAV) identified the liver, spleen, lymph nodes, kidney, lung, and adrenal gland as the primary host tissue sites for viral transcription during acute infection. Combined immunohistochemistry, with a monoclonal antibody recognizing a cytoplasmic antigen of equine mononuclear phagocytes, and in situ hybridization for viral RNA identified most infected cells as mature tissue macrophages. In contrast, in situ hybridization of adherent peripheral blood mononuclear cells co...
Perryman LE, O'Rourke KI, McGuire TC.Six normal and four immunodeficient horses were injected with a cloned variant of equine infectious anemia virus (EIAV). The six normal horses had detectable EIAV in their plasma by 7 days postinjection. During their primary viremic episode, which was accompanied by fever and anemia, maximum titers of EIAV in plasma ranged from 10(3.8) to 10(4.8) 50% tissue culture infective doses per ml. All six normal horses cleared detectable virus from their plasma by 21 to 35 days after injection. Horses with combined immunodeficiency became viremic by 9 days postinjection and also developed anemia. In co...
Lichtenstein DL, Rushlow KE, Cook RF, Raabe ML, Swardson CJ, Kociba GJ, Issel CJ, Montelaro RC.As an important enzyme in DNA synthesis, dUTPase is present in a wide variety of organisms and viruses and has been identified as a component of the equine infectious anemia virus (EIAV) pol gene. The role of EIAV dUTPase, designated DU, in virus replication in vitro and in vivo was investigated with a recently described infectious molecular clone of EIAV. A deletion mutant that was deficient in dUTPase activity was constructed, and its replication kinetics was examined in fetal equine kidney (FEK) cells and primary equine bone marrow macrophage (EBMM) cells. In FEK cells, which are permissive...
Fernandes F, Chen K, Ehrlich LS, Jin J, Chen MH, Medina GN, Symons M, Montelaro R, Donaldson J, Tjandra N, Carter CA.Phosphatidylinositol 4,5-biphosphate [PI(4,5)P(2) ], the predominant phosphoinositide (PI) on the plasma membrane, binds the matrix (MA) protein of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV) with similar affinities in vitro. Interaction with PI(4,5)P(2) is critical for HIV-1 assembly on the plasma membrane. EIAV has been shown to localize in internal compartments; hence, the significance of its interaction with PI(4,5)P(2) is unclear. We therefore investigated the binding in vitro of other PIs to EIAV MA and whether intracellular association with comp...
Ott DE, Coren LV, Sowder RC, Adams J, Nagashima K, Schubert U.Some retroviruses contain monoubiquitinated Gag and do not bud efficiently from cells treated with proteasome inhibitors, suggesting an interaction between the ubiquitin-proteasome system and retrovirus assembly. We examined equine infectious anemia virus (EIAV) particles and found that approximately 2% of the p9(Gag) proteins are monoubiquitinated, demonstrating that this Gag protein interacts with an ubiquitinating activity. Different types of proteasome inhibitors were used to determine if proteasome inactivation affects EIAV release from chronically infected cells. Pulse-chase immunoprecip...
Patnaik A, Chau V, Li F, Montelaro RC, Wills JW.The only retrovirus protein required for the budding of virus-like particles is the Gag protein; however, recent studies of Rous sarcoma virus (RSV) and human immunodeficiency virus have suggested that modification of Gag with ubiquitin (Ub) is also required. As a consequence, the release of these viruses is reduced in the presence of proteasome inhibitors, which indirectly reduce the levels of free Ub within the cell. Here we show that the budding of equine infectious anemia virus (EIAV) from infected equine cells is largely unaffected by these drugs, although use of one inhibitor (MG-132) re...
Threadgill DS, Steagall WK, Flaherty MT, Fuller FJ, Perry ST, Rushlow KE, Le Grice SF, Payne SL.The putative dUTPase domain was deleted from the polymerase (pol) gene of equine infectious anemia virus (EIAV) to produce a recombinant delta DUpol Escherichia coli expression cassette and a delta DU proviral clone. Expression of the recombinant delta DUpol polyprotein yielded a properly processed and enzymatically active reverse transcriptase, as determined by immunoblot analysis and DNA polymerase activity gels. Transfection of delta DU provirus into feline (FEA) cells resulted in production of virus that replicated to wild-type levels in both FEA cells and fetal equine kidney cells. In con...
Stephens RM, Derse D, Rice NR.We isolated and characterized six cDNA clones from an equine infectious anemia virus-infected cell line that displays a Rev-defective phenotype. With the exception of one splice site in one of the clones, all six cDNAs exhibited the same splicing pattern and consisted of four exons. Exon 1 contained the 5' end of the genome; exon 2 contained the tat gene from mid-genome; exon 3 consisted of a small section of env, near the 5' end of the env gene; and exon 4 contained the putative rev open reading frame from the 3' end of the genome. The structures of the cDNAs predict a bicistronic message in ...
Issel CJ, Horohov DW, Lea DF, Adams WV, Hagius SD, McManus JM, Allison AC, Montelaro RC.We report here on a series of vaccine trials to evaluate the effectiveness of an inactivated equine infectious anemia virus (EIAV) whole-virus vaccine and of a subunit vaccine enriched in EIAV envelope glycoproteins. The inactivated vaccine protected 14 of 15 immunized ponies from infection after challenge with at least 10(5) 50% tissue culture-infective doses of the homologous prototype strain of EIAV. In contrast, it failed to prevent infection in any of 15 immunized ponies that were challenged with the heterologous PV strain. Levels of PV virus replication and the development of disease, ho...
Fridell RA, Partin KM, Carpenter S, Cullen BR.Several members of the lentivirus family of complex retroviruses have been shown to encode proteins that are functionally equivalent to the Rev posttranscriptional regulatory protein of human immunodeficiency virus type 1 (HIV-1). Furthermore, the domain organization of HIV-1 Rev, featuring a highly basic N-terminal RNA binding domain and a leucin-rich C-terminal effector domain, has also been shown to be highly conserved among Rev proteins derived from not only the primate but also the ovine and caprine lentiviruses. Although it has therefore appeared highly probable that the lentivirus equin...
O'Rourke K, Perryman LE, McGuire TC.Equine infectious anaemia virus is related by genome sequence homology to human immunodeficiency virus, caprine arthritis-encephalitis virus and visna virus. Failure of the host to mount a strong neutralizing response detectable in vitro or to eliminate persistent infection in vivo characterizes lentivirus infections in the natural host. In this study the specificities and neutralizing activity of antibodies induced during experimental infection with equine infectious anaemia virus were investigated using antiviral ELISA, radioimmunoprecipitation and neutralization assays. ELISA antibody titre...
Harrold SM, Cook SJ, Cook RF, Rushlow KE, Issel CJ, Montelaro RC.Equine infectious anemia virus (EIAV) infection of horses is characterized by recurring cycles of disease and viremia that typically progress to an inapparent infection in which clinical symptoms are absent as host immune responses maintain control of virus replication indefinitely. The dynamics of EIAV viremia and its association with disease cycles have been well characterized, but there has been to date no comprehensive quantitative analyses of the specific tissue sites of EIAV infection and replication in experimentally infected equids during acute disease episodes and during asymptomatic ...
Kono Y, Hirasawa K, Fukunaga Y, Taniguchi T.Horses which had passed a few months to a few years asymptomatically after the last recurrence of equine infectious anemia (EIA) showed a typical febrile response after treatment with the immunosuppressive agent, dexamethasone (DM) or cyclophosphamide (CY). In horses showing a febrile response, EIA virus which had not been neutralized by neutralizing antibody previously produced was propagated. In DM-treated horses it disappeared from the blood soon after pyretolysis and antibody against the virus was produced promptly. In contrast, detectable viremia persisted in CY-treated horses for 10 to 8...
Bogerd HP, Tallmadge RL, Oaks JL, Carpenter S, Cullen BR.Equine infectious anemia virus (EIAV), uniquely among lentiviruses, does not encode a vif gene product. Other lentiviruses, including human immunodeficiency virus type 1 (HIV-1), use Vif to neutralize members of the APOBEC3 (A3) family of intrinsic immunity factors that would otherwise inhibit viral infectivity. This suggests either that equine cells infected by EIAV in vivo do not express active A3 proteins or that EIAV has developed a novel mechanism to avoid inhibition by equine A3 (eA3). Here, we demonstrate that horses encode six distinct A3 proteins, four of which contain a single copy o...
