The pathogenic and vaccine strains of equine infectious anemia virus differentially induce cytokine and chemokine expression and apoptosis in macrophages.
Abstract: The attenuated equine infectious anemia virus (EIAV) vaccine was the first attenuated lentivirus vaccine to be used in a large-scale application and has been used to successfully control the spread of equine infectious anemia (EIA) in China. To better understand the potential role of cytokines in the pathogenesis of EIAV infection and resulting immune response, we used branched DNA technology to compare the mRNA expression levels of 12 cytokines and chemokines, including IL-1α, IL-1β, IL-4, IL-10, TNF-α, IFN-γ, IP-10, IL-8, MIP-1α, MIP-1β, MCP-1, and MCP-2, in equine monocyte-derived macrophages (eMDMs) infected with the EIAV(DLV121) vaccine strain or the parental EIAV(DLV34) pathogenic strain. Infection with EIAV(DLV34) and EIAV(DLV121) both caused changes in the mRNA levels of various cytokines and chemokines in eMDMs. In the early stage of infection with EIAV(DLV34) (0-24h), the expression of the pro-inflammatory cytokines TNF-α and IL-1β were significantly up-regulated, while with EIAV(DLV121), expression of the anti-inflammatory cytokine IL-4 was markedly up-regulated. The effects on the expression of other cytokines and chemokines were similar between these two strains of virus. During the first 4 days after infection, the expression level of IL-4 in cells infected with the pathogenic strain were significantly higher than that in cells infected with the vaccine strain, but the expression of IL-1α and IL-1β induced by the vaccine strain was significantly higher than that observed with the pathogenic strain. In addition, after 4 days of infection with the pathogenic strain, the expression levels of 5 chemokines, but not IP-10, were markedly increased in eMDMs. In contrast, the vaccine strain did not up-regulate these chemokines to this level. Contrary to our expectation, induced apoptosis in eMDMs infected with the vaccine strain was significantly higher than that infected with the pathogenic strain 4 days and 6 days after infection. Together, these results contribute to a greater understanding of the pathogenesis of EIAV and of the mechanisms by which the immune response is induced after EIAV infection.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication Date: 2011-07-14 PubMed ID: 21782860DOI: 10.1016/j.virusres.2011.06.028Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the differential effects of pathogenic and vaccine strains of equine infectious anemia virus (EIAV) on cytokine expression, chemokine expression, and apoptosis in macrophages. The study found that while both strains impact cytokine and chemokine expression, they do so in different ways and to varying degrees. Furthermore, contrary to expectations, the vaccine strain resulted in higher rates of cell death compared to the pathogenic strain.
Objective and Methodology
- The research seeks to understand more about the immune response in cases of equine infectious anemia (EIA) due to EIAV.
- Specifically, the study aimed to compare the effects of a vaccine strain and a parental strain of EIAV on cytokine and chemokine expression, and cell death in macrophages.
- The researchers used branched DNA technologies to compare the mRNA expression levels of 12 cytokines and chemokines in equine monocyte-derived macrophages (eMDMs) infected with these two strains.
- The pathogenic strain used for the study was EIAV(DLV34), while the attenuated vaccine strain was EIAV(DLV121).
Findings on Cytokine and Chemokine Expression
- Infection with both EIAV strains altered the mRNA levels of several cytokines and chemokines in eMDMs, but specific patterns were different.
- In the early stage of infection (0-24h), the pathogenic strain significantly up-regulated pro-inflammatory cytokines TNF-α and IL-1β, whereas the vaccine strain markedly up-regulated the anti-inflammatory cytokine IL-4.
- For the first four days after infection, the pathogenic strain resulted in significantly higher IL-4 expressions, but significantly lower IL-1α and IL-1β expressions, than the vaccine strain.
- The study also found that after four days of infection with the pathogenic strain, the expression levels of five chemokines significantly increased in eMDMs, but this was not the case with the vaccine strain.
Findings on Apoptosis
- Surprisingly, the study found that eMDMs infected with the vaccine strain underwent significantly more apoptosis (cell death) than those infected with the pathogenic strain four and six days after infection.
- The authors suggest this finding is counter to expected results.
Conclusion
- The findings contribute to a better understanding of how the immune response is induced following an EIAV infection and the pathogenesis of EIAV.
- This understanding is crucial as it informs how the EIAV vaccine, being the first attenuated lentivirus vaccine used in large-scale applications, has successfully curbed EIA spread in China.
Cite This Article
APA
Lin YZ, Cao XZ, Li L, Li L, Jiang CG, Wang XF, Ma J, Zhou JH.
(2011).
The pathogenic and vaccine strains of equine infectious anemia virus differentially induce cytokine and chemokine expression and apoptosis in macrophages.
Virus Res, 160(1-2), 274-282.
https://doi.org/10.1016/j.virusres.2011.06.028 Publication
Researcher Affiliations
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
MeSH Terms
- Animals
- Apoptosis
- China
- Cytokines / biosynthesis
- Cytokines / genetics
- Gene Expression Profiling
- Horses
- Infectious Anemia Virus, Equine / immunology
- Infectious Anemia Virus, Equine / pathogenicity
- Macrophages / immunology
- Macrophages / virology
- Vaccines, Attenuated / immunology
- Viral Vaccines / immunology
Citations
This article has been cited 13 times.- Wang XF, Zhang X, Ma W, Li J, Wang X. Host cell restriction factors of equine infectious anemia virus.. Virol Sin 2023 Aug;38(4):485-496.
- Li J, Zhang X, Bai B, Zhang M, Ma W, Lin Y, Wang X, Wang XF. Identification of a Novel Post-transcriptional Transactivator from the Equine Infectious Anemia Virus.. J Virol 2022 Dec 21;96(24):e0121022.
- Zhang X, Li J, Zhang M, Bai B, Ma W, Lin Y, Guo X, Wang XF, Wang X. A Novel, Fully Spliced, Accessory Gene in Equine Lentivirus with Distinct Rev-Responsive Element.. J Virol 2022 Sep 28;96(18):e0098622.
- Wang Y, Ma G, Wang XF, Na L, Guo X, Zhang J, Liu C, Du C, Qi T, Lin Y, Wang X. Keap1 recognizes EIAV early accessory protein Rev to promote antiviral defense.. PLoS Pathog 2022 Feb;18(2):e1009986.
- Ren H, Yin X, Su C, Guo M, Wang XF, Na L, Lin Y, Wang X. Equine lentivirus counteracts SAMHD1 restriction by Rev-mediated degradation of SAMHD1 via the BECN1-dependent lysosomal pathway.. Autophagy 2021 Oct;17(10):2800-2817.
- Lin Y, Wang XF, Wang Y, Du C, Ren H, Liu C, Zhu D, Chen J, Na L, Liu D, Yang Z, Wang X. Env diversity-dependent protection of the attenuated equine infectious anaemia virus vaccine.. Emerg Microbes Infect 2020 Dec;9(1):1309-1320.
- Fatima U, Zhang Z, Zhang H, Wang XF, Xu L, Chu X, Ji S, Wang X. Equine Mx1 Restricts Influenza A Virus Replication by Targeting at Distinct Site of its Nucleoprotein.. Viruses 2019 Dec 2;11(12).
- Du C, Duan Y, Wang XF, Lin Y, Na L, Wang X, Chen K, Wang X. Attenuation of Equine Lentivirus Alters Mitochondrial Protein Expression Profile from Inflammation to Apoptosis.. J Virol 2019 Nov 1;93(21).
- Ji S, Na L, Ren H, Wang Y, Wang X. Equine Myxovirus Resistance Protein 2 Restricts Lentiviral Replication by Blocking Nuclear Uptake of Capsid Protein.. J Virol 2018 Sep 15;92(18).
- Wang HN, Rao D, Fu XQ, Hu MM, Dong JG. Equine infectious anemia virus in China.. Oncotarget 2018 Jan 2;9(1):1356-1364.
- 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.
- 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. Equine viperin restricts equine infectious anemia virus replication by inhibiting the production and/or release of viral Gag, Env, and receptor via distortion of the endoplasmic reticulum.. J Virol 2014 Nov;88(21):12296-310.
- 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.
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