FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Virol / Complex interactions between the major and minor envelope pr...
Journal of virology2010; 84(10); 4898-4911; doi: 10.1128/JVI.02743-09

Complex interactions between the major and minor envelope proteins of equine arteritis virus determine its tropism for equine CD3+ T lymphocytes and CD14+ monocytes.

Abstract: Extensive cell culture passage of the virulent Bucyrus (VB) strain of equine arteritis virus (EAV) to produce the modified live virus (MLV) vaccine strain has altered its tropism for equine CD3(+) T lymphocytes and CD14(+) monocytes. The VB strain primarily infects CD14(+) monocytes and a small subpopulation of CD3(+) T lymphocytes (predominantly CD4(+) T lymphocytes), as determined by dual-color flow cytometry. In contrast, the MLV vaccine strain has a significantly reduced ability to infect CD14(+) monocytes and has lost its capability to infect CD3(+) T lymphocytes. Using a panel of five recombinant chimeric viruses, we demonstrated that interactions among the GP2, GP3, GP4, GP5, and M envelope proteins play a major role in determining the CD14(+) monocyte tropism while the tropism for CD3(+) T lymphocytes is determined by the GP2, GP4, GP5, and M envelope proteins but not the GP3 protein. The data clearly suggest that there are intricate interactions among these envelope proteins that affect the binding of EAV to different cell receptors on CD3(+) T lymphocytes and CD14(+) monocytes. This study shows, for the first time, that CD3(+) T lymphocytes may play an important role in the pathogenesis of equine viral arteritis when horses are infected with the virulent strains of EAV.
Get Full Text
Publication Date: 2010-03-10 PubMed ID: 20219931PubMed Central: PMC2863813DOI: 10.1128/JVI.02743-09Google 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
  • Non-U.S. Gov't

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 paper studies how different strains of Equine Arteritis Virus (EAV) interact with immune cells in horses. Research findings reveal that complex interplays amongst different viral protein envelopes affect the virus’s ability to infect certain types of immune cells.

Background of the study

  • The study builds on a broader understanding of Equine Arteritis Virus (EAV), specifically studying the Bucyrus (VB) strain and its modified live virus (MLV) vaccine strain.
  • EAV is known to primarily infect CD14(+) monocytes and certain T lymphocytes in horses.
  • The researchers aim to understand how various envelope proteins of the virus influence its ability to bind to and infect these immune cells.

Different abilities of VB and MLV strains to infect immune cells

  • The VB strain of EAV mainly infects CD14(+) monocytes and a subpopulation of CD3(+) T lymphocytes (mainly CD4(+) T lymphocytes).
  • In contrast, the MLV vaccine strain shows a reduced ability to infect CD14(+) monocytes and appears incapable of infecting CD3(+) T lymphocytes.

Role of envelope proteins in determining cellular tropism

  • The study uses five recombinant chimeric viruses to demonstrate the influence of the GP2, GP3, GP4, GP5, and M envelope proteins on the infection ability.
  • The particular tropism towards CD14(+) monocytes is determined by interactions among all five envelope proteins mentioned.
  • On the other hand, the tropism for CD3(+) T lymphocytes is driven by the GP2, GP4, GP5, and M envelope proteins, excluding GP3.

Impact of complex interactions of envelope proteins on infection ability

  • The detailed findings show that the combined interplay among these envelope proteins is vital in affecting EAV’s binding to different cell receptors on CD3(+) T lymphocytes and CD14(+) monocytes.
  • This is the first study to suggest that CD3(+) T lymphocytes play a significant role in the progression of equine viral arteritis, particularly when horses are infected with virulent strains of EAV.

Cite This Article

APA
Go YY, Zhang J, Timoney PJ, Cook RF, Horohov DW, Balasuriya UB. (2010). Complex interactions between the major and minor envelope proteins of equine arteritis virus determine its tropism for equine CD3+ T lymphocytes and CD14+ monocytes. J Virol, 84(10), 4898-4911. https://doi.org/10.1128/JVI.02743-09

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 84
Issue: 10
Pages: 4898-4911

Researcher Affiliations

Go, Yun Young
  • 108 Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, USA.
Zhang, Jianqiang
    Timoney, Peter J
      Cook, R Frank
        Horohov, David W
          Balasuriya, Udeni B R

            MeSH Terms

            • Animals
            • CD3 Complex / analysis
            • Cells, Cultured
            • Endothelial Cells / virology
            • Equartevirus / physiology
            • Horses
            • Lipopolysaccharide Receptors / analysis
            • Monocytes / chemistry
            • Monocytes / virology
            • Protein Interaction Mapping
            • T-Lymphocytes / chemistry
            • T-Lymphocytes / virology
            • Viral Envelope Proteins / metabolism
            • Viral Tropism
            • Virus Attachment

            References

            This article includes 68 references
            1. Balasuriya UB, Evermann JF, Hedges JF, McKeirnan AJ, Mitten JQ, Beyer JC, McCollum WH, Timoney PJ, MacLachlan NJ. Serologic and molecular characterization of an abortigenic strain of equine arteritis virus isolated from infective frozen semen and an aborted equine fetus.. J. Am. Vet. Med. Assoc. 213:1586-1589.
              pubmed: 9838958
            2. Balasuriya UB, Heidner HW, Davis NL, Wagner HM, Hullinger PJ, Hedges JF, Williams JC, Johnston RE, Wilson WD, Liu IK, MacLachlan NJ. Alphavirus replicon particles expressing the two major envelope proteins of equine arteritis virus induce high level protection against challenge with virulent virus in vaccinated horses.. Vaccine 20:1609-1617.
              pubmed: 11858869
            3. Balasuriya UB, Leutenegger CM, Topol JB, McCollum WH, Timoney PJ, MacLachlan NJ. Detection of equine arteritis virus by real-time TaqMan reverse transcription-PCR assay.. J. Virol. Methods 101:21-28.
              pubmed: 11849680
            4. Balasuriya UB, MacLachlan NJ. The immune response to equine arteritis virus: potential lessons for other arteriviruses.. Vet. Immunol. Immunopathol. 102:107-129.
              pubmed: 15507299
            5. Balasuriya UB, Snijder EJ, Heidner HW, Zhang J, Zevenhoven-Dobbe JC, Boone JD, McCollum WH, Timoney PJ, MacLachlan NJ. Development and characterization of an infectious cDNA clone of the virulent Bucyrus strain of equine arteritis virus.. J. Gen. Virol. 88:918-924.
              pubmed: 17325365
            6. Balasuriya UB, Snijder EJ, van Dinten LC, Heidner HW, Wilson WD, Hedges JF, Hullinger PJ, MacLachlan NJ. Equine arteritis virus derived from an infectious cDNA clone is attenuated and genetically stable in infected stallions.. Virology 260:201-208.
              pubmed: 10405372
            7. Blanchard-Channell M, Moore PF, Stott JL. Characterization of monoclonal antibodies specific for equine homologues of CD3 and CD5.. Immunology 82:548-554.
              pmc: PMC1414917pubmed: 7530685
            8. Brinton MA. Host factors involved in West Nile virus replication.. Ann. N. Y. Acad. Sci. 951:207-219.
              pubmed: 11797778
            9. Brinton MA, Perelygin AA. Genetic resistance to flaviviruses.. Adv. Virus Res. 60:43-85.
              pubmed: 14689691
            10. Bryans JT, Crowe ME, Doll ER, McCollum WH. Isolation of a filterable agent causing arteritis of horses and abortion by mares; its differentiation from the equine abortion (influenza) virus.. Cornell Vet. 47:3-41.
              pubmed: 13397177
            11. Bryans JT, Doll ER, Knappenberger RE. An outbreak of abortion caused by the equine arteritis virus.. Cornell Vet. 47:69-75.
              pubmed: 13397180
            12. Cavanagh D. Nidovirales: a new order comprising Coronaviridae and Arteriviridae.. Arch. Virol. 142:629-633.
              pubmed: 9349308
            13. Claros MG, von Heijne G. TopPred II: an improved software for membrane protein structure predictions.. Comput. Appl. Biosci. 10:685-686.
              pubmed: 7704669
            14. Crawford TB, Henson JB. Viral arteritis of horses.. Adv. Exp. Med. Biol. 22:175-183.
              pubmed: 4627541
            15. Das PB, Dinh PX, Ansari IH, de Lima M, Osorio FA, Pattnaik AK. The minor envelope glycoproteins GP2a and GP4 of porcine reproductive and respiratory syndrome virus interact with the receptor CD163.. J. Virol. 84:1731-1740.
              pmc: PMC2812361pubmed: 19939927
            16. Del Piero F. Equine viral arteritis.. Vet. Pathol. 37:287-296.
              pubmed: 10896389
            17. Del Piero F, Wilkins PA, Lopez JW, Glaser AL, Dubovi EJ, Schlafer DH, Lein DH. Equine viral arteritis in newborn foals: clinical, pathological, serological, microbiological and immunohistochemical observations.. Equine Vet. J. 29:178-185.
              pubmed: 9234009
            18. de Vries AA, Post SM, Raamsman MJ, Horzinek MC, Rottier PJ. The two major envelope proteins of equine arteritis virus associate into disulfide-linked heterodimers.. J. Virol. 69:4668-4674.
              pmc: PMC189270pubmed: 7609031
            19. de Vries AA, Raamsman MJ, van Dijk HA, Horzinek MC, Rottier PJ. The small envelope glycoprotein (GS) of equine arteritis virus folds into three distinct monomers and a disulfide-linked dimer.. J. Virol. 69:3441-3448.
              pmc: PMC189056pubmed: 7745690
            20. Doll ER, Bryans JT, Wilson JC, McCollum WH. Immunization against equine viral arteritis using modified live virus propagated in cell cultures of rabbit kidney.. Cornell Vet. 48:497-524.
              pubmed: 4971878
            21. Fukunaga Y, Imagawa H, Tabuchi E, Akiyama Y. Clinical and virological findings on experimental equine viral arteritis in horses.. Bull. Equine Res. Inst. 18:110-118.
            22. Glaser AL, de Vries AA, Rottier PJ, Horzinek MC, Colenbrander B. Equine arteritis virus: a review of clinical features and management aspects.. Vet. Q. 18:95-99.
              pubmed: 8903141
            23. Golnik W, Michalska Z, Michalak T. Natural equine viral arteritis in foals.. Schweiz. Arch. Tierheilkd. 123:523-533.
              pubmed: 6274007
            24. Harry TO, McCollum WH. Stability of viability and immunizing potency of lyophilized, modified equine arteritis live-virus vaccine.. Am. J. Vet. Res. 42:1501-1505.
              pubmed: 6275755
            25. Hedges JF, Balasuriya UB, MacLachlan NJ. The open reading frame 3 of equine arteritis virus encodes an immunogenic glycosylated, integral membrane protein.. Virology 264:92-98.
              pubmed: 10544133
            26. Hedges JF, Demaula CD, Moore BD, McLaughlin BE, Simon SI, MacLachlan NJ. Characterization of equine E-selectin.. Immunology 103:498-504.
              pmc: PMC1783268pubmed: 11529941
            27. Ibrahim S, Steinbach F. Non-HLDA8 animal homologue section anti-leukocyte mAbs tested for reactivity with equine leukocytes.. Vet. Immunol. Immunopathol. 119:81-91.
              pubmed: 17692930
            28. Johnson B, Baldwin C, Timoney P, Ely R. Arteritis in equine fetuses aborted due to equine viral arteritis.. Vet. Pathol. 28:248-250.
              pubmed: 1650052
            29. Jones DT. Improving the accuracy of transmembrane protein topology prediction using evolutionary information.. Bioinformatics 23:538-544.
              pubmed: 17237066
            30. Jones DT, Taylor WR, Thornton JM. A model recognition approach to the prediction of all-helical membrane protein structure and topology.. Biochemistry 33:3038-3049.
              pubmed: 8130217
            31. Krogh A, Larsson B, von Heijne G, Sonnhammer EL. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes.. J. Mol. Biol. 305:567-580.
              pubmed: 11152613
            32. Lu Z, Branscum A, Shuck KM, Zhang J, Dubovi E, Timoney PJ, Balasuriya UB. Comparison of two real-time reverse transcription polymerase chain reaction assays for the detection of equine arteritis virus nucleic acid in equine semen and tissue culture fluid.. J. Vet. Diagn. Invest. 20:147-155.
              pubmed: 18319426
            33. Lunn DP, Holmes MA, Antczak DF, Agerwal N, Baker J, Bendali-Ahcene S, Blanchard-Channell M, Byrne KM, Cannizzo K, Davis W, Hamilton MJ, Hannant D, Kondo T, Kydd JH, Monier MC, Moore PF, O'Neil T, Schram BR, Sheoran A, Stott JL, Sugiura T, Vagnoni KE. Report of the Second Equine Leucocyte Antigen Workshop, Squaw valley, California, July 1995.. Vet. Immunol. Immunopathol. 62:101-143.
              pubmed: 9638857
            34. Lunn DP, Holmes MA, Duffus WP. Three monoclonal antibodies identifying antigens on all equine T lymphocytes, and two mutually exclusive T-lymphocyte subsets.. Immunology 74:251-257.
              pmc: PMC1384601pubmed: 1748472
            35. MacLachlan NJ, Balasuriya UB, Rossitto PV, Hullinger PA, Patton JF, Wilson WD. Fatal experimental equine arteritis virus infection of a pregnant mare: immunohistochemical staining of viral antigens.. J. Vet. Diagn. Invest. 8:367-374.
              pubmed: 8844583
            36. Mayall S, Siedek E, Hamblin AS. The anti-human CD21 antibody, BU33, identifies equine B cells.. J. Comp. Pathol. 124:83-87.
              pubmed: 11428193
            37. McCollum WH. Development of a modified virus strain and vaccine for equine viral arteritis.. J. Am. Vet. Med. Assoc. 155:318-322.
              pubmed: 4978804
            38. McCollum WH. Vaccination for equine viral arteritis, p.143-151. In Equine infectious diseases. II. Proceedings of the Second International Conference on Equine Infectious Diseases, Paris 1969.. .
            39. McCollum WH, Doll ER, Wilson JC. The recovery of virus from horses with experimental cases of equine arteritis using monolayer cell cultures of rabbit kidney.. Am. J. Vet. Res. 23:465-469.
            40. McCollum WH, Doll ER, Wilson JC, Johnson CB. Propagation of equine arteritis virus in monolayer cultures of equine kidney.. Am. J. Vet. Res. 22:731-735.
            41. McCollum WH, Doll ER, Wilson JC, Cheatham J. Isolation and propagation of equine arteritis virus in monolayer cell cultures of rabbit kidney.. Cornell Vet. 52:452-458.
              pubmed: 14007366
            42. McCollum WH, Prickett ME, Bryans JT. Temporal distribution of equine arteritis virus in respiratory mucosa, tissues and body fluids of horses infected by inhalation.. Res. Vet. Sci. 12:459-464.
              pubmed: 4999643
            43. McCollum WH, Timoney PJ. Experimental observation on the virulence of isolates of equine arteritis virus.. R&W Publications (Newmarket) Limited, Newmarket, United Kingdom .
            44. McCollum WH, Timoney PJ. The pathogenic qualities of the 1984 strain of equine arteritis virus, p. 34-84. In Grayson Foundation International Conference of Thoroughbred Breeders Organizations, Ireland 1984.. .
            45. McCollum WH, Timoney PJ, Lee JW Jr, Habacker PL, Balasuriya UBR, MacLachlan NJ. Features of an outbreak of equine viral arteritis on a breeding farm associated with abortion and fatal interstitial pneumonia in neonatal foals.. R&W Publications (Newmarket) Limited, Newmarket, United Kingdom .
            46. Molenkamp R, van Tol H, Rozier BC, van der Meer Y, Spaan WJ, Snijder EJ. The arterivirus replicase is the only viral protein required for genome replication and subgenomic mRNA transcription.. J. Gen. Virol. 81:2491-2496.
              pubmed: 10993938
            47. Moore BD, Balasuriya UB, Hedges JF, MacLachlan NJ. Growth characteristics of a highly virulent, a moderately virulent, and an avirulent strain of equine arteritis virus in primary equine endothelial cells are predictive of their virulence to horses.. Virology 298:39-44.
              pubmed: 12093171
            48. Moore BD, Balasuriya UB, Watson JL, Bosio CM, MacKay RJ, MacLachlan NJ. Virulent and avirulent strains of equine arteritis virus induce different quantities of TNF-alpha and other proinflammatory cytokines in alveolar and blood-derived equine macrophages.. Virology 314:662-670.
              pubmed: 14554093
            49. Patton JF, Balasuriya UB, Hedges JF, Schweidler TM, Hullinger PJ, MacLachlan NJ. Phylogenetic characterization of a highly attenuated strain of equine arteritis virus from the semen of a persistently infected standardbred stallion.. Arch. Virol. 144:817-827.
              pubmed: 10365172
            50. Plagemann PG, Moennig V. Lactate dehydrogenase-elevating virus, equine arteritis virus, and simian hemorrhagic fever virus: a new group of positive-strand RNA viruses.. Adv. Virus Res. 41:99-192.
              pmc: PMC7131515pubmed: 1315480
            51. Prickett ME, McCollum WH, Bryans JT. The gross and microscopic pathology observed in horses experimentally infected with the equine arteritis virus, p. 265-272. In Equine infectious diseases. III. Proceedings of the Third International Conference on Equine Infectious Diseases, Paris 1972.. .
            52. Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints.. Am. J. Hyg. 27:493-497.
            53. Senne DA, Pearson JE, Carbrey EA. Equine viral arteritis: a standard procedure for the virus neutralization test and comparison of results of a proficiency test performed at five laboratories, p. 29-34. In Proceedings of the 89th Annual Meeting of the United States Animal Health Association.. .
            54. Snijder EJ, Dobbe JC, Spaan WJ. Heterodimerization of the two major envelope proteins is essential for arterivirus infectivity.. J. Virol. 77:97-104.
              pmc: PMC140607pubmed: 12477814
            55. Snijder EJ, Meulenberg JJ. The molecular biology of arteriviruses.. J. Gen. Virol. 79:961-979.
              pubmed: 9603311
            56. Snijder EJ, Spaan WJ. Arteriviruses, p. 1337-1355. In D. M. Knipe and P. M. Howley (ed.), Fields virology, 5th ed.. .
            57. Snijder EJ, van Tol H, Pedersen KW, Raamsman MJ, de Vries AA. Identification of a novel structural protein of arteriviruses.. J. Virol. 73:6335-6345.
              pmc: PMC112712pubmed: 10400725
            58. Timoney PJ, McCollum WH. Equine viral arteritis.. Vet. Clin. North Am. Equine Pract. 9:295-309.
              pmc: PMC7134676pubmed: 8395325
            59. Timoney PJ, Umphenour NW, McCollum WH. Safety evaluation of commercial modified live equine arteritis virus vaccine for use in stallions, p. 19-27. In Equine infectious diseases. V. Proceedings of the Fifth International Conference on Equine Infectious Diseases, Lexington 1987.. .
            60. Vaala WE, Hamir AN, Dubovi EJ, Timoney PJ, Ruiz B. Fatal, congenitally acquired infection with equine arteritis virus in a neonatal thoroughbred.. Equine Vet. J. 24:155-158.
              pubmed: 1316264
            61. van Aken D, Zevenhoven-Dobbe J, Gorbalenya AE, Snijder EJ. Proteolytic maturation of replicase polyprotein pp1a by the nsp4 main proteinase is essential for equine arteritis virus replication and includes internal cleavage of nsp7.. J. Gen. Virol. 87:3473-3482.
              pubmed: 17098961
            62. Wagner HM, Balasuriya UB, MacLachlan NJ. The serologic response of horses to equine arteritis virus as determined by competitive enzyme-linked immunosorbent assays (c-ELISAs) to structural and non-structural viral proteins.. Comp. Immunol. Microbiol. Infect. Dis. 26:251-260.
              pubmed: 12676125
            63. Wieringa R, De Vries AA, Post SM, Rottier PJ. Intra- and intermolecular disulfide bonds of the GP2b glycoprotein of equine arteritis virus: relevance for virus assembly and infectivity.. J. Virol. 77:12996-13004.
              pmc: PMC296049pubmed: 14645556
            64. Wieringa R, de Vries AA, Raamsman MJ, Rottier PJ. Characterization of two new structural glycoproteins, GP(3) and GP(4), of equine arteritis virus.. J. Virol. 76:10829-10840.
              pmc: PMC136612pubmed: 12368326
            65. Wieringa R, de Vries AA, Rottier PJ. Formation of disulfide-linked complexes between the three minor envelope glycoproteins (GP2b, GP3, and GP4) of equine arteritis virus.. J. Virol. 77:6216-6226.
              pmc: PMC155002pubmed: 12743278
            66. Zhang J, Go YY, MacLachlan NJ, Meade BJ, Timoney PJ, Balasuriya UB. Amino acid substitutions in the structural or nonstructural proteins of a vaccine strain of equine arteritis virus are associated with its attenuation.. Virology 378:355-362.
              pubmed: 18619638
            67. Zhang J, Timoney PJ, MacLachlan NJ, McCollum WH, Balasuriya UB. Persistent equine arteritis virus infection in HeLa cells.. J. Virol. 82:8456-8464.
              pmc: PMC2519626pubmed: 18579588
            68. Ziebuhr J, Snijder EJ, Gorbalenya AE. Virus-encoded proteinases and proteolytic processing in the Nidovirales.. J. Gen. Virol. 81:853-879.
              pubmed: 10725411
            Subscribe to our newsletter
            Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.