FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of virology2008; 82(19); 9425-9432; doi: 10.1128/JVI.01142-08

An equine infectious anemia virus variant superinfects cells through novel receptor interactions.

Abstract: Wild-type strains of equine infectious anemia virus (EIAV) prevent superinfection of previously infected cells. A variant strain of virus that spontaneously arose during passage, EIAV(vMA-1c), can circumvent this mechanism in some cells, such as equine dermis (ED) cells, but not in others, such as equine endothelial cells. EIAV(vMA-1c) superinfection of ED cells results in a buildup of unintegrated viral DNA and rapid killing of the cell monolayer. Here, we examined the mechanism of resistance that is used by EIAV to prevent superinfection and explored the means by which EIAV(vMA-1c) overcomes this restriction. We found that the cellular receptor used by EIAV, equine lentivirus receptor 1 (ELR1), remains on the surface of cells chronically infected with EIAV, suggesting that wild-type EIAV interferes with superinfection by masking ELR1. The addition of soluble wild-type SU protein to the medium during infection blocked infection by wild-type strains of virus, implicating SU as the viral protein responsible for interfering with virion entry into previously infected cells. Additionally, interference of wild-type EIAV binding to ELR1 by the addition of either anti-ELR1 antibodies or the ELR1 ectodomain prevented entry of the wild-type strains of EIAV into two permissive cell populations. Many of these same interference treatments prevented EIAV(vMA-1c) infection of endothelial cells but only modestly affected the ability of EIAV(vMA-1c) to enter and kill previously infected ED cells. These findings indicate that EIAV(vMA-1c) retains the ability to use ELR1 for entry and suggest that this virus can interact with an additional, unidentified receptor to superinfect ED cells.
Get Full Text
Publication Date: 2008-07-30 PubMed ID: 18667522PubMed Central: PMC2546952DOI: 10.1128/JVI.01142-08Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural

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 investigates how a variant strain of Equine Infectious Anemia virus (EIAV) is able to infect cells that are already infected with the virus, a phenomenon known as ‘superinfection’. The study finds that this variant strain, EIAV(vMA-1c), achieves superinfection by interacting with an unidentified additional receptor in certain types of cells, suggesting a novel mechanism adopted by the virus.

Background and Objective

  • The study began with the understanding that wild-type (naturally occurring) strains of EIAV usually block superinfection in previously affected cells. This prevention is believed to be due to the virus’ ability to mask the equine lentivirus receptor 1 (ELR1), which EIAV uses to enter cells.
  • The researchers were intrigued by a variant strain of the virus, EIAV(vMA-1c), that arose spontaneously and was observed to override this block in certain cell types, leading to their superinfection.
  • The aim of the research was to examine how wild-type EIAV prevents superinfection, and determine how EIAV(vMA-1c) was able to overcome this barrier.

Findings

  • The cellular receptor used by EIAV, ELR1, was found to be present on the surface of cells chronically infected with EIAV, indicating that wild-type EIAV’s ability to prevent superinfection works by masking ELR1.
  • It was observed that adding soluble wild-type SU protein during infection blocked the infection by wild-type strains, implicating SU as the viral protein responsible for blocking virion entry into already infected cells.
  • Interference treatments such as anti-ELR1 antibodies or the ELR1 ectodomain that blocked wild-type EIAV from binding to ELR1 also blocked virus entry in permissive cell populations.
  • Interestingly, these interference treatments only slightly affected EIAV(vMA-1c)’s ability to enter previously infected cells, suggesting that EIAV(vMA-1c) uses ELR1 for entry but may also interact with an additional, unidentified receptor to achieve superinfection within these cells.

Conclusion

  • The research supports the belief that EIAV employs a strategy to prevent superinfection in already infected cells by interacting with the ELR1 receptor.
  • EIAV(vMA-1c)’s ability to overcome this blockage and superinfect certain types of cells suggests that it may rely on an alternative receptor, beyond ELR1, for this purpose.
  • Further research is needed to identify this additional receptor used by EIAV(vMA-1c) for superinfection and to explore its potential implications for the progression and treatment of EIAV infections.

Cite This Article

APA
Brindley MA, Zhang B, Montelaro RC, Maury W. (2008). An equine infectious anemia virus variant superinfects cells through novel receptor interactions. J Virol, 82(19), 9425-9432. https://doi.org/10.1128/JVI.01142-08

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 82
Issue: 19
Pages: 9425-9432

Researcher Affiliations

Brindley, Melinda A
  • 3-612 Bowen Science Bldg., Dept. Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Zhang, Baoshan
    Montelaro, Ronald C
      Maury, Wendy

        MeSH Terms

        • Animals
        • Cell Line
        • Culture Media / metabolism
        • DNA, Viral / genetics
        • Dermis / virology
        • Fibroblasts / metabolism
        • Horses
        • Humans
        • Hydrogen-Ion Concentration
        • Infectious Anemia Virus, Equine / genetics
        • Infectious Anemia Virus, Equine / metabolism
        • Kinetics
        • Membrane Glycoproteins / metabolism
        • Phenotype
        • RNA, Small Interfering / metabolism
        • Receptors, Virus / metabolism
        • Viral Envelope Proteins / metabolism

        Grant Funding

        • 9R56 AI07326 / NIAID NIH HHS
        • T32 A1007533 / PHS HHS

        References

        This article includes 31 references
        1. Adkins HB, Blacklow SC, Young JA. Two functionally distinct forms of a retroviral receptor explain the nonreciprocal receptor interference among subgroups B, D, and E avian leukosis viruses.. J Virol 2001 Apr;75(8):3520-6.
          pmc: PMC114843pubmed: 11264341doi: 10.1128/JVI.75.8.3520-3526.2001google scholar: lookup
        2. Ball JM, Rushlow KE, Issel CJ, Montelaro RC. Detailed mapping of the antigenicity of the surface unit glycoprotein of equine infectious anemia virus by using synthetic peptide strategies.. J Virol 1992 Feb;66(2):732-42.
          pmc: PMC240772pubmed: 1370556doi: 10.1128/JVI.66.2.732-742.1992google scholar: lookup
        3. Bock M, Heinkelein M, Lindemann D, Rethwilm A. Cells expressing the human foamy virus (HFV) accessory Bet protein are resistant to productive HFV superinfection.. Virology 1998 Oct 10;250(1):194-204.
          pubmed: 9770433doi: 10.1006/viro.1998.9362google scholar: lookup
        4. Brindley MA, Maury W. Endocytosis and a low-pH step are required for productive entry of equine infectious anemia virus.. J Virol 2005 Dec;79(23):14482-8.
          pmc: PMC1287591pubmed: 16282447doi: 10.1128/JVI.79.23.14482-14488.2005google scholar: lookup
        5. Brindley MA, Maury W. Equine infectious anemia virus entry occurs through clathrin-mediated endocytosis.. J Virol 2008 Feb;82(4):1628-37.
          pmc: PMC2258727pubmed: 18057237doi: 10.1128/JVI.01754-07google scholar: lookup
        6. Carpenter S, Chesebro B. Change in host cell tropism associated with in vitro replication of equine infectious anemia virus.. J Virol 1989 Jun;63(6):2492-6.
          pmc: PMC250709pubmed: 2470916doi: 10.1128/JVI.63.6.2492-2496.1989google scholar: lookup
        7. Delwart EL, Panganiban AT. Role of reticuloendotheliosis virus envelope glycoprotein in superinfection interference.. J Virol 1989 Jan;63(1):273-80.
          pmc: PMC247682pubmed: 2535733doi: 10.1128/JVI.63.1.273-280.1989google scholar: lookup
        8. DuBridge RB, Tang P, Hsia HC, Leong PM, Miller JH, Calos MP. Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system.. Mol Cell Biol 1987 Jan;7(1):379-87.
          pmc: PMC365079pubmed: 3031469doi: 10.1128/mcb.7.1.379-387.1987google scholar: lookup
        9. Dzuris JL, Zhu W, Kapkov D, Golovkina TV, Ross SR. Expression of mouse mammary tumor virus envelope protein does not prevent superinfection in vivo or in vitro.. Virology 1999 Oct 25;263(2):418-26.
          pubmed: 10544114doi: 10.1006/viro.1999.9967google scholar: lookup
        10. Heard JM, Danos O. An amino-terminal fragment of the Friend murine leukemia virus envelope glycoprotein binds the ecotropic receptor.. J Virol 1991 Aug;65(8):4026-32.
          pmc: PMC248833pubmed: 2072445doi: 10.1128/JVI.65.8.4026-4032.1991google scholar: lookup
        11. Jobbagy Z, Garfield S, Baptiste L, Eiden MV, Anderson WB. Subcellular redistribution of Pit-2 P(i) transporter/amphotropic leukemia virus (A-MuLV) receptor in A-MuLV-infected NIH 3T3 fibroblasts: involvement in superinfection interference.. J Virol 2000 Mar;74(6):2847-54.
          pmc: PMC111775pubmed: 10684301doi: 10.1128/jvi.74.6.2847-2854.2000google scholar: lookup
        12. Lindwasser OW, Chaudhuri R, Bonifacino JS. Mechanisms of CD4 downregulation by the Nef and Vpu proteins of primate immunodeficiency viruses.. Curr Mol Med 2007 Mar;7(2):171-84.
          pubmed: 17346169doi: 10.2174/156652407780059177google scholar: lookup
        13. Maury W, Wright PJ, Bradley S. Characterization of a cytolytic strain of equine infectious anemia virus.. J Virol 2003 Feb;77(4):2385-99.
          pmc: PMC141072pubmed: 12551976doi: 10.1128/jvi.77.4.2385-2399.2003google scholar: lookup
        14. Maury WJ, Carpenter S, Graves K, Chesebro B. Cellular and viral specificity of equine infectious anemia virus Tat transactivation.. Virology 1994 May 1;200(2):632-42.
          pubmed: 8178449doi: 10.1006/viro.1994.1226google scholar: lookup
        15. Mealey RH, Leib SR, Pownder SL, McGuire TC. Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection.. J Virol 2004 Sep;78(17):9295-305.
          pmc: PMC506964pubmed: 15308724doi: 10.1128/JVI.78.17.9295-9305.2004google scholar: lookup
        16. Michel N, Allespach I, Venzke S, Fackler OT, Keppler OT. The Nef protein of human immunodeficiency virus establishes superinfection immunity by a dual strategy to downregulate cell-surface CCR5 and CD4.. Curr Biol 2005 Apr 26;15(8):714-23.
          pubmed: 15854903doi: 10.1016/j.cub.2005.02.058google scholar: lookup
        17. Miller DG, Miller AD. A family of retroviruses that utilize related phosphate transporters for cell entry.. J Virol 1994 Dec;68(12):8270-6.
          pmc: PMC237294pubmed: 7966619doi: 10.1128/JVI.68.12.8270-8276.1994google scholar: lookup
        18. Mitrophanous K, Yoon S, Rohll J, Patil D, Wilkes F, Kim V, Kingsman S, Kingsman A, Mazarakis N. Stable gene transfer to the nervous system using a non-primate lentiviral vector.. Gene Ther 1999 Nov;6(11):1808-18.
          pubmed: 10602376doi: 10.1038/sj.gt.3301023google scholar: lookup
        19. Murphy SL, Chung-Landers M, Honczarenko M, Gaulton GN. Linkage of reduced receptor affinity and superinfection to pathogenesis of TR1.3 murine leukemia virus.. J Virol 2006 May;80(9):4601-9.
          pmc: PMC1472024pubmed: 16611920doi: 10.1128/JVI.80.9.4601-4609.2006google scholar: lookup
        20. Nethe M, Berkhout B, van der Kuyl AC. Retroviral superinfection resistance.. Retrovirology 2005 Aug 18;2:52.
          pmc: PMC1224871pubmed: 16107223doi: 10.1186/1742-4690-2-52google scholar: lookup
        21. Oaks JL, Ulibarri C, Crawford TB. Endothelial cell infection in vivo by equine infectious anaemia virus.. J Gen Virol 1999 Sep;80 ( Pt 9):2393-2397.
          pubmed: 10501492doi: 10.1099/0022-1317-80-9-2393google scholar: lookup
        22. O'Rourke K, Perryman LE, McGuire TC. Antiviral, anti-glycoprotein and neutralizing antibodies in foals with equine infectious anaemia virus.. J Gen Virol 1988 Mar;69 ( Pt 3):667-74.
          pubmed: 3351480doi: 10.1099/0022-1317-69-3-667google scholar: lookup
        23. Payne SL, Rausch J, Rushlow K, Montelaro RC, Issel C, Flaherty M, Perry S, Sellon D, Fuller F. Characterization of infectious molecular clones of equine infectious anaemia virus.. J Gen Virol 1994 Feb;75 ( Pt 2):425-9.
          pubmed: 8113766doi: 10.1099/0022-1317-75-2-425google scholar: lookup
        24. Payne SL, Rushlow K, Dhruva BR, Issel CJ, Montelaro RC. Localization of conserved and variable antigenic domains of equine infectious anemia virus envelope glycoproteins using recombinant env-encoded protein fragments produced in Escherichia coli.. Virology 1989 Oct;172(2):609-15.
          pubmed: 2552661doi: 10.1016/0042-6822(89)90203-1google scholar: lookup
        25. Sellon DC, Perry ST, Coggins L, Fuller FJ. Wild-type equine infectious anemia virus replicates in vivo predominantly in tissue macrophages, not in peripheral blood monocytes.. J Virol 1992 Oct;66(10):5906-13.
          pmc: PMC241467pubmed: 1382143doi: 10.1128/JVI.66.10.5906-5913.1992google scholar: lookup
        26. Stevenson M, Meier C, Mann AM, Chapman N, Wasiak A. Envelope glycoprotein of HIV induces interference and cytolysis resistance in CD4+ cells: mechanism for persistence in AIDS.. Cell 1988 May 6;53(3):483-96.
          pubmed: 2966682doi: 10.1016/0092-8674(88)90168-7google scholar: lookup
        27. Tallmadge RL, Brindley MA, Salmans J, Mealey RH, Maury W, Carpenter S. Development and characterization of an equine infectious anemia virus Env-pseudotyped reporter virus.. Clin Vaccine Immunol 2008 Jul;15(7):1138-40.
          pmc: PMC2446648pubmed: 18448619doi: 10.1128/CVI.00088-08google scholar: lookup
        28. Van Hoeven NS, Miller AD. Use of different but overlapping determinants in a retrovirus receptor accounts for non-reciprocal interference between xenotropic and polytropic murine leukemia viruses.. Retrovirology 2005 Dec 15;2:76.
          pmc: PMC1325250pubmed: 16354307doi: 10.1186/1742-4690-2-76google scholar: lookup
        29. 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.
          pmc: PMC1563805pubmed: 16873261doi: 10.1128/JVI.00252-06google scholar: lookup
        30. Zhang B, Jin S, Jin J, Li F, Montelaro RC. A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus.. Proc Natl Acad Sci U S A 2005 Jul 12;102(28):9918-23.
          pmc: PMC1174982pubmed: 15985554doi: 10.1073/pnas.0501560102google scholar: lookup
        31. Zhang B, Sun C, Jin S, Cascio M, Montelaro RC. Mapping of equine lentivirus receptor 1 residues critical for equine infectious anemia virus envelope binding.. J Virol 2008 Feb;82(3):1204-13.
          pmc: PMC2224449pubmed: 18032504doi: 10.1128/JVI.01393-07google scholar: lookup

        Citations

        This article has been cited 5 times.
        1. Ong HH, Liu J, Oo Y, Thong M, Wang Y, Chow VT. Prolonged Primary Rhinovirus Infection of Human Nasal Epithelial Cells Diminishes the Viral Load of Secondary Influenza H3N2 Infection via the Antiviral State Mediated by RIG-I and Interferon-Stimulated Genes. Cells 2023 Apr 13;12(8).
          doi: 10.3390/cells12081152pubmed: 37190061google scholar: lookup
        2. 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.
          doi: 10.1186/s13567-014-0082-ypubmed: 25106750google scholar: lookup
        3. 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.
          doi: 10.1371/journal.pone.0079299pubmed: 24278125google scholar: lookup
        4. DaPalma T, Doonan BP, Trager NM, Kasman LM. A systematic approach to virus-virus interactions. Virus Res 2010 Apr;149(1):1-9.
          doi: 10.1016/j.virusres.2010.01.002pubmed: 20093154google scholar: lookup
        5. Brindley MA, Widrlechner MP, McCoy JA, Murphy P, Hauck C, Rizshsky L, Nikolau B, Maury W. Inhibition of lentivirus replication by aqueous extracts of Prunella vulgaris. Virol J 2009 Jan 20;6:8.
          doi: 10.1186/1743-422X-6-8pubmed: 19154592google scholar: lookup
        Subscribe to our newsletter
        Join 99,850 horse owners like you who receive our email updates on horse health and nutrition.