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J Virol. 1996 August; 70(8): 5143–5152.
PMCID: PMC190469

The HeLa cell receptor for enterovirus 70 is decay-accelerating factor (CD55).


Enterovirus 70 (EV70) is a recently emerged human pathogen belonging to the family Picornaviridae. The ability of EV70 to infect a wide variety of nonprimate cell lines in vitro is unique among human enteroviruses. The importance of virus receptors as determinants of viral host range and tropism led us to study the host cell receptor for this unusual picornavirus. We produced a monoclonal antibody (MAb), EVR1, which bound to the surface of HeLa cells and protected them against infection by EV70 but not by poliovirus or by coxsackievirus B3. This antibody also inhibited the binding of [35S]EV70 to HeLa cells. MAb EVR1 did not bind to monkey kidney (LLC-MK2) cells, nor did it protect these cells against virus infection. In Western immunoassays and in immunoprecipitations, MAb EVR1 identified a HeLa cell glycoprotein of approximately 75 kDa that is attached to the cell membrane by a glycosyl-phosphatidylinositol (GPI) anchor. Decay-accelerating factor (DAF, CD55) is a 70- to 75-kDa GPI-anchored membrane protein that is involved in the regulation of complement and has also been shown to function as a receptor for several enteroviruses. MAb EVR1 bound to Chinese hamster ovary (CHO) cells constitutively expressing human DAF. Anti-DAF MAbs inhibited EV70 binding to HeLa cells and protected them against EV70 infection. Transient expression of human DAF in murine NIH 3T3 cells resulted in binding of labelled EV70 and stably, transformed NIH 3T3 cells expressing DAF were able to support virus replication. These data indicate that the HeLa cell receptor for EV70 is DAF.

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Selected References

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  • Abraham G, Colonno RJ. Many rhinovirus serotypes share the same cellular receptor. J Virol. 1984 Aug;51(2):340–345. [PMC free article] [PubMed]
  • Bass DM, Greenberg HB. Strategies for the identification of icosahedral virus receptors. J Clin Invest. 1992 Jan;89(1):3–9. [PMC free article] [PubMed]
  • Bergelson JM, Chan M, Solomon KR, St John NF, Lin H, Finberg RW. Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6245–6248. [PubMed]
  • Bergelson JM, Finberg RW. Integrins as receptors for virus attachment and cell entry. Trends Microbiol. 1993 Nov;1(8):287–288. [PubMed]
  • Bergelson JM, Mohanty JG, Crowell RL, St John NF, Lublin DM, Finberg RW. Coxsackievirus B3 adapted to growth in RD cells binds to decay-accelerating factor (CD55). J Virol. 1995 Mar;69(3):1903–1906. [PMC free article] [PubMed]
  • Bergelson JM, Shepley MP, Chan BM, Hemler ME, Finberg RW. Identification of the integrin VLA-2 as a receptor for echovirus 1. Science. 1992 Mar 27;255(5052):1718–1720. [PubMed]
  • Bergelson JM, St John N, Kawaguchi S, Chan M, Stubdal H, Modlin J, Finberg RW. Infection by echoviruses 1 and 8 depends on the alpha 2 subunit of human VLA-2. J Virol. 1993 Nov;67(11):6847–6852. [PMC free article] [PubMed]
  • Berinstein A, Roivainen M, Hovi T, Mason PW, Baxt B. Antibodies to the vitronectin receptor (integrin alpha V beta 3) inhibit binding and infection of foot-and-mouth disease virus to cultured cells. J Virol. 1995 Apr;69(4):2664–2666. [PMC free article] [PubMed]
  • Clarkson NA, Kaufman R, Lublin DM, Ward T, Pipkin PA, Minor PD, Evans DJ, Almond JW. Characterization of the echovirus 7 receptor: domains of CD55 critical for virus binding. J Virol. 1995 Sep;69(9):5497–5501. [PMC free article] [PubMed]
  • Coyne KE, Hall SE, Thompson S, Arce MA, Kinoshita T, Fujita T, Anstee DJ, Rosse W, Lublin DM. Mapping of epitopes, glycosylation sites, and complement regulatory domains in human decay accelerating factor. J Immunol. 1992 Nov 1;149(9):2906–2913. [PubMed]
  • Darougar S, Monnickendam MA, Woodland RM. Management and prevention of ocular viral and chlamydial infections. Crit Rev Microbiol. 1989;16(5):369–418. [PubMed]
  • Davitz MA, Low MG, Nussenzweig V. Release of decay-accelerating factor (DAF) from the cell membrane by phosphatidylinositol-specific phospholipase C (PIPLC). Selective modification of a complement regulatory protein. J Exp Med. 1986 May 1;163(5):1150–1161. [PMC free article] [PubMed]
  • Dimock K, Harnish DG, Sisson G, Leung WC, Rawls WE. Synthesis of virus-specific polypeptides and genomic RNA during the replicative cycle of Pichinde virus. J Virol. 1982 Jul;43(1):273–283. [PMC free article] [PubMed]
  • Engvall E, Perlmann P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry. 1971 Sep;8(9):871–874. [PubMed]
  • Greve JM, Davis G, Meyer AM, Forte CP, Yost SC, Marlor CW, Kamarck ME, McClelland A. The major human rhinovirus receptor is ICAM-1. Cell. 1989 Mar 10;56(5):839–847. [PubMed]
  • Hansen MB, Nielsen SE, Berg K. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods. 1989 May 12;119(2):203–210. [PubMed]
  • Higgins PG. Enteroviral conjunctivitis and its neurological complications. Arch Virol. 1982;73(2):91–101. [PubMed]
  • Hofer F, Gruenberger M, Kowalski H, Machat H, Huettinger M, Kuechler E, Blaas D. Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1839–1842. [PubMed]
  • Huber SA. VCAM-1 is a receptor for encephalomyocarditis virus on murine vascular endothelial cells. J Virol. 1994 Jun;68(6):3453–3458. [PMC free article] [PubMed]
  • Johnson RT. The Soriano Award Lecture. Emerging infections of the nervous system. J Neurol Sci. 1994 Jun;124(1):3–14. [PubMed]
  • King SL, Cunningham JA, Finberg RW, Bergelson JM. Echovirus 1 interaction with the isolated VLA-2 I domain. J Virol. 1995 May;69(5):3237–3239. [PMC free article] [PubMed]
  • Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. [PubMed]
  • Kono R, Sasagawa A, Ishii K, Sugiura S, Ochi M. Pandemic of new type of conjunctivitis. Lancet. 1972 Jun 3;1(7762):1191–1194. [PubMed]
  • Kono R, Tajiri E, Miyamura K, Sasagawa A, Tsuruhara T. Hemoagglutination and hemagglutination inhibition tests with enterovirus type 70. J Clin Microbiol. 1978 Jun;7(6):595–598. [PMC free article] [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Lublin DM, Atkinson JP. Decay-accelerating factor: biochemistry, molecular biology, and function. Annu Rev Immunol. 1989;7:35–58. [PubMed]
  • Lublin DM, Coyne KE. Phospholipid-anchored and transmembrane versions of either decay-accelerating factor or membrane cofactor protein show equal efficiency in protection from complement-mediated cell damage. J Exp Med. 1991 Jul 1;174(1):35–44. [PMC free article] [PubMed]
  • Medof ME, Lublin DM, Holers VM, Ayers DJ, Getty RR, Leykam JF, Atkinson JP, Tykocinski ML. Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2007–2011. [PubMed]
  • Medof ME, Walter EI, Roberts WL, Haas R, Rosenberry TL. Decay accelerating factor of complement is anchored to cells by a C-terminal glycolipid. Biochemistry. 1986 Nov 4;25(22):6740–6747. [PubMed]
  • Medof ME, Walter EI, Rutgers JL, Knowles DM, Nussenzweig V. Identification of the complement decay-accelerating factor (DAF) on epithelium and glandular cells and in body fluids. J Exp Med. 1987 Mar 1;165(3):848–864. [PMC free article] [PubMed]
  • Mendelsohn CL, Wimmer E, Racaniello VR. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell. 1989 Mar 10;56(5):855–865. [PubMed]
  • Mims CA. Virus receptors and cell tropisms. J Infect. 1986 May;12(3):199–203. [PubMed]
  • Nicholson-Weller A. Decay accelerating factor (CD55). Curr Top Microbiol Immunol. 1992;178:7–30. [PubMed]
  • Nicholson-Weller A, Burge J, Austen KF. Purification from guinea pig erythrocyte stroma of a decay-accelerating factor for the classical c3 convertase, C4b,2a. J Immunol. 1981 Nov;127(5):2035–2039. [PubMed]
  • Nicholson-Weller A, Burge J, Fearon DT, Weller PF, Austen KF. Isolation of a human erythrocyte membrane glycoprotein with decay-accelerating activity for C3 convertases of the complement system. J Immunol. 1982 Jul;129(1):184–189. [PubMed]
  • Nicholson-Weller A, Wang CE. Structure and function of decay accelerating factor CD55. J Lab Clin Med. 1994 Apr;123(4):485–491. [PubMed]
  • Norkin LC. Virus receptors: implications for pathogenesis and the design of antiviral agents. Clin Microbiol Rev. 1995 Apr;8(2):293–315. [PMC free article] [PubMed]
  • de Verdugo UR, Selinka HC, Huber M, Kramer B, Kellermann J, Hofschneider PH, Kandolf R. Characterization of a 100-kilodalton binding protein for the six serotypes of coxsackie B viruses. J Virol. 1995 Nov;69(11):6751–6757. [PMC free article] [PubMed]
  • Roivainen M, Piirainen L, Hovi T, Virtanen I, Riikonen T, Heino J, Hyypiä T. Entry of coxsackievirus A9 into host cells: specific interactions with alpha v beta 3 integrin, the vitronectin receptor. Virology. 1994 Sep;203(2):357–365. [PubMed]
  • Shafren DR, Bates RC, Agrez MV, Herd RL, Burns GF, Barry RD. Coxsackieviruses B1, B3, and B5 use decay accelerating factor as a receptor for cell attachment. J Virol. 1995 Jun;69(6):3873–3877. [PMC free article] [PubMed]
  • Shepley MP, Racaniello VR. A monoclonal antibody that blocks poliovirus attachment recognizes the lymphocyte homing receptor CD44. J Virol. 1994 Mar;68(3):1301–1308. [PMC free article] [PubMed]
  • Shulman M, Wilde CD, Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. [PubMed]
  • Spicer AP, Seldin MF, Gendler SJ. Molecular cloning and chromosomal localization of the mouse decay-accelerating factor genes. Duplicated genes encode glycosylphosphatidylinositol-anchored and transmembrane forms. J Immunol. 1995 Sep 15;155(6):3079–3091. [PubMed]
  • Stanway G. Structure, function and evolution of picornaviruses. J Gen Virol. 1990 Nov;71(Pt 11):2483–2501. [PubMed]
  • Staunton DE, Merluzzi VJ, Rothlein R, Barton R, Marlin SD, Springer TA. A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses. Cell. 1989 Mar 10;56(5):849–853. [PubMed]
  • Sugita Y, Uzawa M, Tomita M. Isolation of decay-accelerating factor (DAF) from rabbit erythrocyte membranes. J Immunol Methods. 1987 Nov 23;104(1-2):123–130. [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PubMed]
  • Utagawa ET, Miyamura K, Mukoyama A, Kono R. Neuraminidase-sensitive erythrocyte receptor for enterovirus type 70. J Gen Virol. 1982 Nov;63(Pt 1):141–148. [PubMed]
  • Ward T, Pipkin PA, Clarkson NA, Stone DM, Minor PD, Almond JW. Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method. EMBO J. 1994 Nov 1;13(21):5070–5074. [PubMed]
  • White DJ, Oglesby T, Liszewski MK, Tedja I, Hourcade D, Wang MW, Wright L, Wallwork J, Atkinson JP. Expression of human decay accelerating factor or membrane cofactor protein genes on mouse cells inhibits lysis by human complement. Transplant Proc. 1992 Apr;24(2):474–476. [PubMed]
  • White JM, Littman DR. Viral receptors of the immunoglobulin superfamily. Cell. 1989 Mar 10;56(5):725–728. [PubMed]
  • Wright PW, Strauss GH, Langford MP. Acute hemorrhagic conjunctivitis. Am Fam Physician. 1992 Jan;45(1):173–178. [PubMed]
  • Yoshii T, Natori K, Kono R. Replication of enterovirus 70 in non-primate cell cultures. J Gen Virol. 1977 Sep;36(3):377–384. [PubMed]

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