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Home / Equine Research Bank / PLoS One / The soluble form of the EIAV receptor encoded by an alternat...
PloS one2013; 8(11); e79299; doi: 10.1371/journal.pone.0079299

The soluble form of the EIAV receptor encoded by an alternative splicing variant inhibits EIAV infection of target cells.

Abstract: Equine lentivirus receptor 1 (ELR1) has been identified as the sole receptor for equine infectious anemia virus (EIAV) and is a member of the tumor necrosis factor receptor (TNFR) superfamily. In addition to the previously described membrane-associated form of ELR1, two other major alternative splicing variant mRNAs were identified in equine monocyte-derived macrophages (eMDMs). One major spliced species (ELR1-IN) contained an insertion of 153 nt, which resulted in a premature stop codon situated 561 nt upstream of the predicted membrane spanning domain. The other major species (ELR1-DE) has a deletion of 109 nt that causes a shift of the open reading frame and generates a stop codon 312 nt downstream. Because ELR1-DE presumably encodes a peptide of a mere 23 residues, only ELR1-IN was further analyzed. The expression of a soluble form of ELR1 (sELR1) by ELR1-IN was confirmed by Western blot and immunofluorescence analyses. Similar to ELR1, the transcription level of ELR1-IN varied among individual horses and at different time points in the same individuals. The ratio of ELR1-IN mRNA species to ELR1 mRNA was approximately 1∶2.5. Pre-incubation of the recombinant sELR1 with EIAV significantly inhibited EIAV infection in equine macrophages, the primary in vivo target cell of the virus. Fetal equine dermal (FED) cells are susceptible to EIAV in vitro, and the replication of EIAV in FED cells transiently transfected with ELR1-IN was markedly reduced when compared with replication in cells transfected with the empty vector. Finally, the expression levels of both forms of the EIAV receptor were significantly regulated by infection with this virus. Taken together, our data indicate that sELR1 acts as a secreted cellular factor that inhibits EIAV infection in host cells.
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Publication Date: 2013-11-22 PubMed ID: 24278125PubMed Central: PMC3838338DOI: 10.1371/journal.pone.0079299Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article investigates how an alternative form of the equine lentivirus receptor (ELR1), produced through variant mRNA splicing, is capable of inhibiting infection by the equine infectious anemia virus (EIAV).

Introductory Background

  • Email virus (EIAV) infection occurs in horses, and it is linked to the equine lentivirus receptor 1 (ELR1), a member of the tumor necrosis factor receptor (TNFR) superfamily.
  • Two other versions of ELR1, produced via alternative splicing of mRNA, were identified in the study conducted on equine monocyte-derived macrophages (eMDMs).

Alternative Splicing and ELR1 Variants

  • The two variants were named ELR1-IN (with a 153 nt insertion) and ELR1-DE (with a 109 nt deletion). The abc where nt refers to nucleotides.
  • ELR1-DE’s deletion resulted in the shifting of the open reading frame and the generation of a stop codon, presumably resulting in a peptide with only 23 residues. Hence, only ELR1-IN was further studied.

Expression of Soluble ELR1 and its Role

  • The article reports that the ELR1-IN variant encodes a soluble form of ELR1 (sELR1), as confirmed by Western blot and immunofluorescence analyses.
  • The transcription rate of ELR1-IN varied among horses and changed over time for individual horses. In comparison with ELR1 mRNA, the ratio of the ELR1-IN mRNA species was estimated to be 1:2.5.
  • The pre-incubation of recombinant sELR1 with EIAV significantly inhibited the EIAV infection in equine macrophages, which are the primary target cells for this virus inside the body.

Effect on EIAV Replication and Infection

  • This study also notes that fetal equine dermal (FED) cells, which are susceptible to EIAV in the lab, showed greatly reduced replication of EIAV when they were temporarily transfected with ELR1-IN compared to control cells.
  • Moreover, the expression levels of both the normal and soluble forms of the EIAV receptor were significantly affected by the presence of the virus. This suggests that there is a reciprocal relationship between EIAV infection and ELR1 expression.

Conclusion of the Study

  • The study concludes that the sELR1, encoded by ELR1-IN, acts as a secreted cellular factor that inhibits EIAV infection. This insight into the role of ELR1-IN and sELR1 in preventing EIAV infection could have important implications for developing therapeutic strategies against this equine virus.

Cite This Article

APA
Lin YZ, Yang F, Zhang SQ, Sun LK, Wang XF, Du C, Zhou JH. (2013). The soluble form of the EIAV receptor encoded by an alternative splicing variant inhibits EIAV infection of target cells. PLoS One, 8(11), e79299. https://doi.org/10.1371/journal.pone.0079299

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 11
Pages: e79299
PII: e79299

Researcher Affiliations

Lin, Yue-Zhi
  • Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China.
Yang, Fei
    Zhang, Shu-Qin
      Sun, Liu-Ke
        Wang, Xue-Feng
          Du, Cheng
            Zhou, Jian-Hua

              MeSH Terms

              • Alternative Splicing / genetics
              • Animals
              • Cell Line
              • Horses
              • Humans
              • Infectious Anemia Virus, Equine
              • Protein Precursors / genetics
              • RNA, Messenger / genetics
              • Receptors, Virus / genetics
              • Tumor Necrosis Factor-alpha / genetics

              Conflict of Interest Statement

              The authors have declared that no competing interests exist.

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              Citations

              This article has been cited 4 times.
              1. Peterson TA, MacLean AG. Current and Future Therapeutic Strategies for Lentiviral Eradication from Macrophage Reservoirs.. J Neuroimmune Pharmacol 2019 Mar;14(1):68-93.
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                doi: 10.1002/pro.2634pubmed: 25559821google scholar: lookup
              4. Ma J, Wang SS, Lin YZ, Liu HF, Liu Q, Wei HM, Wang XF, Wang YH, Du C, Kong XG, Zhou JH, Wang X. 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 2014 Aug 9;45(1):82.
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