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Veterinary research2014; 45(1); 82; doi: 10.1186/s13567-014-0082-y

Infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (EIAV) strain induces a strong resistance to the infection by a virulent EIAV strain.

Abstract: 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, induced a strong resistance to subsequent infection by a pathogenic strain, EIAVUK3. Further experiments indicate that the expression of the soluble EIAV receptor sELR1, Toll-like receptor 3 (TLR3) and interferon β (IFNβ) was up-regulated in eMDM infected with EIAVFDDV13 compared with eMDM infected with EIAVUK3. Stimulating eMDM with poly I:C resulted in similar resistance to EIAV infection as induced by EIAVFDDV13 and was correlated with enhanced TLR3, sELR1 and IFNβ expression. The knock down of TLR3 mRNA significantly impaired poly I:C-stimulated resistance to EIAV, greatly reducing the expression of sELR1 and IFNβ and lowered the level of infection resistance induced by EIAVFDDV13. These results indicate that the induction of restraining infection by EIAVFDDV13 in macrophages is partially mediated through the up-regulated expression of the soluble viral receptor and IFNβ, and that the TLR3 pathway activation plays an important role in the development of an EIAV-resistant intracellular environment.
Publication Date: 2014-08-09 PubMed ID: 25106750PubMed Central: PMC4283155DOI: 10.1186/s13567-014-0082-yGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research explores how introducing the attenuated Chinese equine infectious anemia virus (EIAV) strain into equine monocyte-derived macrophages (cells commonly associated with immune response) can induce strong resistance against a more pathogenic EIAV strain.

Study and Methodology

The research was derived from the successful use of the Chinese attenuated EIAV vaccine to protect equines from EIA disease in China. In the study, an attenuated strain of EIAV known as EIAVFDDV13 was introduced into equine monocyte-derived macrophages (eMDM), cells that play a critical role in the immune system of horses. EIAVFDDV13 was observed to induce strong resistance against a subsequent infection by a pathogenic strain, EIAVUK3.

  • During the experiment, it was noticed that the expression of certain molecules and receptors like the soluble EIAV receptor sELR1, the Toll-like receptor 3 (TLR3), and interferon β (IFNβ) was increased in eMDM after exposure to EIAVFDDV13, compared to those infected with EIAVUK3.
  • The researchers also tried stimulating eMDM with poly I:C, an immune response stimulator, and found that it induced similar resistance to EIAV as EIAVFDDV13 and increased the expression of TLR3, sELR1, and IFNβ.
  • The role of TLR3 in infection resistance was further confirmed by reducing its mRNA expression, which resulted in significant impairment of poly I:C-stimulated resistance to EIAV infection, lower expression of sELR1 and IFNβ, and decreased resistance induced by EIAVFDDV13.

Findings and Significance

The study found that EIAVFDDV13 could induce resistance to the pathogenic EIAV strain in eMDM. This was related to an up-regulation in the expression of sELR1 and IFNβ and the activation of the TLR3 pathway.

  • This means that the attenuated EIAV strain can prepare the horse’s immune system to gear up responses, including IFNβ and sELR1 against a more dangerous EIAV strain.
  • The TLR3 pathway was found to be critical to this resistance, and reduction of its activity resulted in a drop in the EIAV resistance level.

This research provides valuable insights on how the Indonesian EIAV vaccine might work, paving the way for further studies to test if these findings could be used in the development of effective vaccines.

Cite This Article

APA
Ma J, Wang SS, Lin YZ, Liu HF, Liu Q, Wei HM, Wang XF, Wang YH, Du C, Kong XG, Zhou JH, Wang X. (2014). Infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (EIAV) strain induces a strong resistance to the infection by a virulent EIAV strain. Vet Res, 45(1), 82. https://doi.org/10.1186/s13567-014-0082-y

Publication

ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English
Volume: 45
Issue: 1
Pages: 82
PII: 82

Researcher Affiliations

Ma, Jian
    Wang, Shan-Shan
      Lin, Yue-Zhi
        Liu, Hai-Fang
          Liu, Qiang
            Wei, Hua-Mian
              Wang, Xue-Feng
                Wang, Yu-Hong
                  Du, Cheng
                    Kong, Xian-Gang
                      Zhou, Jian-Hua
                      • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, Heilongjiang, China. Jianhua_uc@126.com.
                      Wang, Xiaojun

                        MeSH Terms

                        • Animals
                        • Disease Resistance
                        • Enzyme-Linked Immunosorbent Assay / veterinary
                        • Equine Infectious Anemia / genetics
                        • Equine Infectious Anemia / immunology
                        • Equine Infectious Anemia / virology
                        • Gene Expression Regulation
                        • Horse Diseases / genetics
                        • Horse Diseases / immunology
                        • Horse Diseases / virology
                        • Horses
                        • Infectious Anemia Virus, Equine / genetics
                        • Infectious Anemia Virus, Equine / physiology
                        • Interferon-beta / genetics
                        • Interferon-beta / metabolism
                        • Macrophages / immunology
                        • Real-Time Polymerase Chain Reaction / veterinary
                        • Receptors, Virus / genetics
                        • Receptors, Virus / metabolism
                        • Reverse Transcriptase Polymerase Chain Reaction / veterinary
                        • Toll-Like Receptor 3 / genetics
                        • Toll-Like Receptor 3 / metabolism
                        • Viral Vaccines / immunology

                        References

                        This article includes 34 references
                        1. Leroux C, Cadoré JL, Montelaro RC. Equine Infectious Anemia Virus (EIAV): what has HIV's country cousin got to tell us?. Vet Res 2004 Jul-Aug;35(4):485-512.
                          doi: 10.1051/vetres:2004020pubmed: 15236678google scholar: lookup
                        2. Maury W. Monocyte maturation controls expression of equine infectious anemia virus.. J Virol 1994 Oct;68(10):6270-9.
                        3. Hammond SA, Raabe ML, Issel CJ, Montelaro RC. Evaluation of antibody parameters as potential correlates of protection or enhancement by experimental vaccines to equine infectious anemia virus.. Virology 1999 Sep 30;262(2):416-30.
                          doi: 10.1006/viro.1999.9939pubmed: 10502520google scholar: lookup
                        4. Harrold SM, Cook SJ, Cook RF, Rushlow KE, Issel CJ, Montelaro RC. Tissue sites of persistent infection and active replication of equine infectious anemia virus during acute disease and asymptomatic infection in experimentally infected equids.. J Virol 2000 Apr;74(7):3112-21.
                        5. Craigo JK, Durkin S, Sturgeon TJ, Tagmyer T, Cook SJ, Issel CJ, Montelaro RC. Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines.. Vaccine 2007 Jan 15;25(5):834-45.
                        6. Ma J, Shi N, Jiang CG, Lin YZ, Wang XF, Wang S, Lv XL, Zhao LP, Shao YM, Kong XG, Zhou JH, Shen RX. A proviral derivative from a reference attenuated EIAV vaccine strain failed to elicit protective immunity.. Virology 2011 Feb 5;410(1):96-106.
                          doi: 10.1016/j.virol.2010.10.032pubmed: 21094511google scholar: lookup
                        7. Meng Q, Lin Y, Ma J, Ma Y, Zhao L, Li S, Liang H, Zhou J, Shen R, Zhang X, Shao Y. A pilot study on an attenuated Chinese EIAV vaccine inducing broadly neutralizing antibodies.. Arch Virol 2011 Aug;156(8):1455-62.
                          doi: 10.1007/s00705-011-0992-1pubmed: 21499906google scholar: lookup
                        8. Maury W, Wright PJ, Bradley S. Characterization of a cytolytic strain of equine infectious anemia virus.. J Virol 2003 Feb;77(4):2385-99.
                        9. Brindley MA, Zhang B, Montelaro RC, Maury W. An equine infectious anemia virus variant superinfects cells through novel receptor interactions.. J Virol 2008 Oct;82(19):9425-32.
                          doi: 10.1128/JVI.01142-08pmc: PMC2546952pubmed: 18667522google scholar: lookup
                        10. Jiang CG, Gao X, Ma J, Lin YZ, Wang XF, Zhao LP, Hua YP, Liu D, Zhou JH. C-terminal truncation of the transmembrane protein of an attenuated lentiviral vaccine alters its in vitro but not in vivo replication and weakens its potential pathogenicity.. Virus Res 2011 Jun;158(1-2):235-45.
                        11. Ma J, Jiang C, Lin Y, Wang X, Zhao L, Xiang W, Shao Y, Shen R, Kong X, Zhou J. In vivo evolution of the gp90 gene and consistently low plasma viral load during transient immune suppression demonstrate the safety of an attenuated equine infectious anemia virus (EIAV) vaccine.. Arch Virol 2009;154(5):867-73.
                          doi: 10.1007/s00705-009-0378-9pubmed: 19363668google scholar: lookup
                        12. Cook RF, Cook SJ, Berger SL, Leroux C, Ghabrial NN, Gantz M, Bolin PS, Mousel MR, Montelaro RC, Issel CJ. Enhancement of equine infectious anemia virus virulence by identification and removal of suboptimal nucleotides.. Virology 2003 Sep 1;313(2):588-603.
                          doi: 10.1016/S0042-6822(03)00351-9pubmed: 12954224google scholar: lookup
                        13. Cook RF, Cook SJ, Li FL, Montelaro RC, Issel CJ. Development of a multiplex real-time reverse transcriptase-polymerase chain reaction for equine infectious anemia virus (EIAV).. J Virol Methods 2002 Aug;105(1):171-9.
                          doi: 10.1016/S0166-0934(02)00101-5pubmed: 12176154google scholar: lookup
                        14. Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg 1938;27:493–497.
                        15. Lin YZ, Yang F, Zhang SQ, Sun LK, Wang XF, Du C, Zhou JH. The soluble form of the EIAV receptor encoded by an alternative splicing variant inhibits EIAV infection of target cells.. PLoS One 2013;8(11):e79299.
                        16. Wu W, Blythe DC, Loyd H, Mealey RH, Tallmadge RL, Dorman KS, Carpenter S. Decreased infectivity of a neutralization-resistant equine infectious anemia virus variant can be overcome by efficient cell-to-cell spread.. J Virol 2011 Oct;85(19):10421-4.
                          doi: 10.1128/JVI.05349-11pmc: PMC3196457pubmed: 21752904google scholar: lookup
                        17. Parker LC, Prince LR, Sabroe I. Translational mini-review series on Toll-like receptors: networks regulated by Toll-like receptors mediate innate and adaptive immunity.. Clin Exp Immunol 2007 Feb;147(2):199-207.
                        18. Baccala R, Hoebe K, Kono DH, Beutler B, Theofilopoulos AN. TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity.. Nat Med 2007 May;13(5):543-51.
                          doi: 10.1038/nm1590pubmed: 17479100google scholar: lookup
                        19. Flür K, Allam R, Zecher D, Kulkarni OP, Lichtnekert J, Schwarz M, Beutler B, Vielhauer V, Anders HJ. Viral RNA induces type I interferon-dependent cytokine release and cell death in mesangial cells via melanoma-differentiation-associated gene-5: Implications for viral infection-associated glomerulonephritis.. Am J Pathol 2009 Nov;175(5):2014-22.
                          doi: 10.2353/ajpath.2009.080585pmc: PMC2774065pubmed: 19850889google scholar: lookup
                        20. Nethe M, Berkhout B, van der Kuyl AC. Retroviral superinfection resistance.. Retrovirology 2005 Aug 18;2:52.
                          doi: 10.1186/1742-4690-2-52pmc: PMC1224871pubmed: 16107223google scholar: lookup
                        21. Wildum S, Schindler M, Münch J, Kirchhoff F. Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection.. J Virol 2006 Aug;80(16):8047-59.
                          doi: 10.1128/JVI.00252-06pmc: PMC1563805pubmed: 16873261google scholar: lookup
                        22. Haim H, Si Z, Madani N, Wang L, Courter JR, Princiotto A, Kassa A, DeGrace M, McGee-Estrada K, Mefford M, Gabuzda D, Smith AB 3rd, Sodroski J. Soluble CD4 and CD4-mimetic compounds inhibit HIV-1 infection by induction of a short-lived activated state.. PLoS Pathog 2009 Apr;5(4):e1000360.
                        23. Daar ES, Li XL, Moudgil T, Ho DD. High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates.. Proc Natl Acad Sci U S A 1990 Sep;87(17):6574-8.
                          doi: 10.1073/pnas.87.17.6574pmc: PMC54579pubmed: 2395859google scholar: lookup
                        24. Sullivan N, Sun Y, Binley J, Lee J, Barbas CF 3rd, Parren PW, Burton DR, Sodroski J. Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies.. J Virol 1998 Aug;72(8):6332-8.
                        25. Zhou Y, Wang X, Liu M, Hu Q, Song L, Ye L, Zhou D, Ho W. A critical function of toll-like receptor-3 in the induction of anti-human immunodeficiency virus activities in macrophages.. Immunology 2010 Sep;131(1):40-9.
                        26. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.. Nat Immunol 2010 May;11(5):373-84.
                          doi: 10.1038/ni.1863pubmed: 20404851google scholar: lookup
                        27. Kawai T, Akira S. Innate immune recognition of viral infection.. Nat Immunol 2006 Feb;7(2):131-7.
                          doi: 10.1038/ni1303pubmed: 16424890google scholar: lookup
                        28. Swanson CL, Wilson TJ, Strauch P, Colonna M, Pelanda R, Torres RM. Type I IFN enhances follicular B cell contribution to the T cell-independent antibody response.. J Exp Med 2010 Jul 5;207(7):1485-500.
                          doi: 10.1084/jem.20092695pmc: PMC2901065pubmed: 20566717google scholar: lookup
                        29. Le Bon A, Schiavoni G, D'Agostino G, Gresser I, Belardelli F, Tough DF. Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo.. Immunity 2001 Apr;14(4):461-70.
                          doi: 10.1016/S1074-7613(01)00126-1pubmed: 11336691google scholar: lookup
                        30. Zhu J, Huang X, Yang Y. Type I IFN signaling on both B and CD4 T cells is required for protective antibody response to adenovirus.. J Immunol 2007 Mar 15;178(6):3505-10.
                          doi: 10.4049/jimmunol.178.6.3505pubmed: 17339445google scholar: lookup
                        31. Cucak H, Yrlid U, Reizis B, Kalinke U, Johansson-Lindbom B. Type I interferon signaling in dendritic cells stimulates the development of lymph-node-resident T follicular helper cells.. Immunity 2009 Sep 18;31(3):491-501.
                          doi: 10.1016/j.immuni.2009.07.005pubmed: 19733096google scholar: lookup
                        32. King C, Sprent J. Emerging cellular networks for regulation of T follicular helper cells.. Trends Immunol 2012 Feb;33(2):59-65.
                          doi: 10.1016/j.it.2011.11.006pubmed: 22209178google scholar: lookup
                        33. Craigo JK, Barnes S, Zhang B, Cook SJ, Howe L, Issel CJ, Montelaro RC. An EIAV field isolate reveals much higher levels of subtype variability than currently reported for the equine lentivirus family.. Retrovirology 2009 Oct 20;6:95.
                          doi: 10.1186/1742-4690-6-95pmc: PMC2770520pubmed: 19843328google scholar: lookup
                        34. Qi X, Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Shen R, Wang F, Kong X, Su Z, Zhou J. Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAV FDDV13.. Virus Genes 2010 Aug;41(1):86-98.
                          doi: 10.1007/s11262-010-0491-6pubmed: 20526660google scholar: lookup

                        Citations

                        This article has been cited 9 times.
                        1. Pezzanite LM, Chow L, Griffenhagen GM, Bass L, Goodrich LR, Impastato R, Dow S. Distinct differences in immunological properties of equine orthobiologics revealed by functional and transcriptomic analysis using an activated macrophage readout system. Front Vet Sci 2023;10:1109473.
                          doi: 10.3389/fvets.2023.1109473pubmed: 36876001google scholar: lookup
                        2. Pezzanite L, Chow L, Hendrickson D, Gustafson DL, Russell Moore A, Stoneback J, Griffenhagen GM, Piquini G, Phillips J, Lunghofer P, Dow S, Goodrich LR. Evaluation of Intra-Articular Amikacin Administration in an Equine Non-inflammatory Joint Model to Identify Effective Bactericidal Concentrations While Minimizing Cytotoxicity. Front Vet Sci 2021;8:676774.
                          doi: 10.3389/fvets.2021.676774pubmed: 34095281google scholar: lookup
                        3. Peterson TA, MacLean AG. Current and Future Therapeutic Strategies for Lentiviral Eradication from Macrophage Reservoirs. J Neuroimmune Pharmacol 2019 Mar;14(1):68-93.
                          doi: 10.1007/s11481-018-9814-5pubmed: 30317409google scholar: lookup
                        4. de Pablo-Maiso L, Doménech A, Echeverría I, Gómez-Arrebola C, de Andrés D, Rosati S, Gómez-Lucia E, Reina R. Prospects in Innate Immune Responses as Potential Control Strategies against Non-Primate Lentiviruses. Viruses 2018 Aug 17;10(8).
                          doi: 10.3390/v10080435pubmed: 30126090google scholar: lookup
                        5. Wang HN, Rao D, Fu XQ, Hu MM, Dong JG. Equine infectious anemia virus in China. Oncotarget 2018 Jan 2;9(1):1356-1364.
                          doi: 10.18632/oncotarget.20381pubmed: 29416700google scholar: lookup
                        6. Liu Q, Ma J, Wang XF, Xiao F, Li LJ, Zhang JE, Lin YZ, Du C, He XJ, Wang X, Zhou JH. Infection with equine infectious anemia virus vaccine strain EIAVDLV121 causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response. Vet Immunol Immunopathol 2016 Feb;170:30-40.
                          doi: 10.1016/j.vetimm.2016.01.006pubmed: 26832985google scholar: lookup
                        7. Linde P, Chow L, Sabino I, Williams Z, Impastato R, Dow S, Pezzanite L. Innate immune pathway activation to modulate mesenchymal stromal cell (MSC) interactions with synovium and cartilage. Front Bioeng Biotechnol 2025;13:1605148.
                          doi: 10.3389/fbioe.2025.1605148pubmed: 40861855google scholar: lookup
                        8. Cardeti G, Manna G, Cersini A, Nardini R, Rosati S, Reina R, Cittadini M, Sittinieri S, Altigeri A, Marcario GA, Scicluna MT. Horse Innate Immunity in the Control of Equine Infectious Anemia Virus Infection: A Preliminary Study. Viruses 2024 Nov 21;16(12).
                          doi: 10.3390/v16121804pubmed: 39772115google scholar: lookup
                        9. Chen K, Zhou B, Wang X, Yang G, Lin Y, Wang X, Du C, Wang X. Equine lentivirus Gag protein degrades mitochondrial antiviral signaling protein via the E3 ubiquitin ligase Smurf1. J Virol 2025 Jan 31;99(1):e0169124.
                          doi: 10.1128/jvi.01691-24pubmed: 39665545google scholar: lookup