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MeSH Review

Enterovirus B, Human

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Disease relevance of Enterovirus B, Human


High impact information on Enterovirus B, Human

  • Identification of the integrin VLA-2 as a receptor for echovirus 1 [6].
  • Echovirus 16 was recovered from a throat swab of one hospitalized player and from the CSF of another [7].
  • HBB alone also protects Coxsackie A 9, but not echo virus 9-infected animals, whereas guanidine alone is ineffective in either case [8].
  • Mouse cells transfected with the CD55 clone bind echovirus 7, and this binding is blocked by the anti-receptor mAb [9].
  • Integrins are cell surface receptors for several microbial pathogens including echovirus 1 (EV1), a picornavirus [10].

Chemical compound and disease context of Enterovirus B, Human

  • This was accompanied by a large rise in the creatine phosphokinase level and a rise in echovirus 9 titers from 1:16 to greater than 1:256 during a two-week period [11].
  • The arginine at position 17 of VPg could not be exchanged with any other amino acid without loss of viability, whereas the lysine at position 20, an amino acid conserved among all known polioviruses, coxsackieviruses, and echoviruses, was replaceable with several neutral amino acids and even with glutamic acid [12].
  • Echoviruses bind heparan sulfate at the cell surface [13].
  • This possibility was confirmed by the clinical course of ECG change, with elevated CPK and lactate dehydrogenase and a slightly elevated antibody titer for echovirus [14].
  • Purified recombinant protein containing SCR domains 2, 3, and 4, but lacking the serine/threonine rich region, was shown to block infection of susceptible cells by echovirus 7 [15].

Biological context of Enterovirus B, Human

  • Binding sites for both collagen and echovirus 1 have been mapped to the I domain within the alpha2 subunit of the VLA-2 alpha2beta1 heterodimer [16].
  • In this study, we use surface plasmon resonance to study the affinity and kinetics of the interaction of echovirus 11 with its cellular receptor decay-accelerating factor (CD55) [17].
  • Nucleotide sequences of nine epidemic strains [belonging to echovirus serotypes 4 (E4), 7 (E7) and 30 (E30)] in the two genomic regions (300 nt of VP1 and 520 nt of 3D polymerase) were compared to prototype and field strains, and phylogenetic trees were generated from alignments [18].
  • In this study, RNA extracts of CNS tissue from 28 patients with ALS-MND and 7 controls were assayed by nested polymerase chain reaction (PCR) using primers to the 5'-untranslated region (UTR) of the enterovirus (EV) genome which is highly conserved between EVs including PV, echovirus and coxsackie viruses [19].
  • In particular, there was no evidence for associations between ICA status at diagnosis and either sex, race, family history of IDDM, HLA-DR phenotype, antibody titers to Coxsackie B viruses, immunoglobulin levels, C-peptide and glycosylated hemoglobin concentrations, or insulin requirements [20].

Anatomical context of Enterovirus B, Human

  • HeLa cells specifically lost the capacity to bind echovirus 7 when treated with phosphatidylinositol-specific phospholipase C, an enzyme that releases GPI-anchored proteins from the cell surface, indicating that the virus receptor, like DAF, is a GPI-anchored protein [21].
  • Despite great similarity in the structure and replication of coxsackievirus B3 (CBV3), echovirus 1 (EV1), and poliovirus 1 (PV1), the ability of these viruses to infect human peripheral blood mononuclear cells (PBMC), and B (Raji), T (Molt-4) and monocytic (U-937) cell lines differed markedly [22].
  • Since E9/Barty does not replicate or replicates only poorly in mice older than about 5 days, and expression of the vitronectin receptor is reported to be down-regulated in striated muscle tissue during development, it is suggested that susceptibility of mice to this echovirus infection is controlled by the availability of alpha(v)beta3 integrin [23].
  • Primary endothelial cells were highly susceptible to several serotypes of enteroviruses (coxsackievirus A13, echoviruses 6, 7, 11, 30, and poliovirus 1) [24].
  • Lymphocytotoxicity power, as well as the ability of each drug to influence secondary humoral (against sheep red blood cells or diphtheria anatoxin) or cell-mediated (against PPD and Coxsackie A9 virus) immunity were searched [25].

Gene context of Enterovirus B, Human

  • Human cardiac inflammatory responses triggered by Coxsackie B viruses are mainly Toll-like receptor (TLR) 8-dependent [26].
  • In contrast to FAC localization and collagen adhesion results, VLA-2-dependent binding and infection by echovirus were unaffected by either alpha 2 cytoplasmic domain deletion or exchange with other cytoplasmic domains [27].
  • Remarkably, RasGAP is cleaved during infections with different strains of coxsackievirus B3 as well as with echovirus 11 and echovirus 12, yielding a 104-kDa protein fragment [28].
  • Specifically, it was found that CAV1, -11, -13, -15, -17 to -22, and -24 are classified together with polioviruses and enterovirus 70, whereas the rest of the CAVs are classified along with coxsackie B viruses, echoviruses, and the rest of the other enteroviruses [29].
  • This latter finding was supported by a greater frequency of antibodies to Coxsackie-B viruses in the DR4 cases at presentation [30].

Analytical, diagnostic and therapeutic context of Enterovirus B, Human

  • We present here a structure for echovirus (EV) type 12 bound to DAF using cryo-negative stain transmission electron microscopy and three-dimensional image reconstruction to 16-A resolution, which we interpreted using the atomic structures of EV11 and DAF [31].
  • Recent sequence analysis revealed that the human pathogen echovirus 22 (EV22) is genetically distant from all the other picornaviruses studied to date (T. Hyypiä, C. Horsnell, M. Maaronen, M. Khan, N. Kalkkinen, P. Auvinen, L. Kinnunen, and G. Stanway, Proc. Natl. Acad. Sci. USA 89:8847-8851, 1992) [32].
  • Filters containing diatomaceous earth modified by in situ precipitation of a combination of ferric chloride and aluminum chloride adsorbed greater than 80% of enteroviruses (poliovirus 1, echovirus 5, and coxsackievirus B5) and coliphage MS2 present in tap water at ambient pH (7.8 to 8.3), even after filtration of 100 liters of tap water [33].
  • The virus isolates were initially identified as echovirus 4 (E4) on the basis of immunofluorescence staining with anti-E4 and anti-E30 (Bastianni prototype) monoclonal antibodies [34].
  • The echovirus type 11 IgM ELISA appears to have considerable laboratory diagnostic potential when a rising antibody level cannot be demonstrated in paired sera or when virus is not cultured [35].


  1. Maternal first-trimester enterovirus infection and future risk of type 1 diabetes in the exposed fetus. Viskari, H.R., Roivainen, M., Reunanen, A., Pitkäniemi, J., Sadeharju, K., Koskela, P., Hovi, T., Leinikki, P., Vilja, P., Tuomilehto, J., Hyöty, H. Diabetes (2002) [Pubmed]
  2. Echovirus 1 endocytosis into caveosomes requires lipid rafts, dynamin II, and signaling events. Pietiäinen, V., Marjomäki, V., Upla, P., Pelkmans, L., Helenius, A., Hyypiä, T. Mol. Biol. Cell (2004) [Pubmed]
  3. A monoclonal antibody specific for the cellular receptor for the group B coxsackieviruses. Hsu, K.H., Lonberg-Holm, K., Alstein, B., Crowell, R.L. J. Virol. (1988) [Pubmed]
  4. Tyrosine phosphorylation events during coxsackievirus B3 replication. Huber, M., Selinka, H.C., Kandolf, R. J. Virol. (1997) [Pubmed]
  5. Absence of germline infection in male mice following intraventricular injection of adenovirus. Peters, A.H., Drumm, J., Ferrell, C., Roth, D.A., Roth, D.M., McCaman, M., Novak, P.L., Friedman, J., Engler, R., Braun, R.E. Mol. Ther. (2001) [Pubmed]
  6. Identification of the integrin VLA-2 as a receptor for echovirus 1. Bergelson, J.M., Shepley, M.P., Chan, B.M., Hemler, M.E., Finberg, R.W. Science (1992) [Pubmed]
  7. Aseptic meningitis among members of a high school football team. An outbreak associated with echovirus 16 infection. Baron, R.C., Hatch, M.H., Kleeman, K., MacCormack, J.N. JAMA (1982) [Pubmed]
  8. Successful treatment of enterovirus-infected mice by 2-(alpha-hydroxybenzyl)-benzimidazole and guanidine. Eggers, H.J. J. Exp. Med. (1976) [Pubmed]
  9. Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method. Ward, T., Pipkin, P.A., Clarkson, N.A., Stone, D.M., Minor, P.D., Almond, J.W. EMBO J. (1994) [Pubmed]
  10. Structural and functional analysis of integrin alpha2I domain interaction with echovirus 1. Xing, L., Huhtala, M., Pietiäinen, V., Käpylä, J., Vuorinen, K., Marjomäki, V., Heino, J., Johnson, M.S., Hyypiä, T., Cheng, R.H. J. Biol. Chem. (2004) [Pubmed]
  11. Acute rhabdomyolysis associated with an echovirus 9 infection. Josselson, J., Pula, T., Sadler, J.H. Arch. Intern. Med. (1980) [Pubmed]
  12. Mutational analysis of the genome-linked protein VPg of poliovirus. Kuhn, R.J., Tada, H., Ypma-Wong, M.F., Semler, B.L., Wimmer, E. J. Virol. (1988) [Pubmed]
  13. Echoviruses bind heparan sulfate at the cell surface. Goodfellow, I.G., Sioofy, A.B., Powell, R.M., Evans, D.J. J. Virol. (2001) [Pubmed]
  14. A case of myocarditis associated with IDDM. Mokuno, T., Sawai, Y., Oda, N., Mano, T., Hayakawa, N., Kato, R., Itoh, Y., Shimazaki, K., Kotake, M., Nakai, A., Hiramitsu, S., Itoh, M., Morimoto, S., Nagasaka, A. Diabetes Care (1996) [Pubmed]
  15. Interaction between echovirus 7 and its receptor, decay-accelerating factor (CD55): evidence for a secondary cellular factor in A-particle formation. Powell, R.M., Ward, T., Evans, D.J., Almond, J.W. J. Virol. (1997) [Pubmed]
  16. Echovirus 1 interaction with the human very late antigen-2 (integrin alpha2beta1) I domain. Identification of two independent virus contact sites distinct from the metal ion-dependent adhesion site. King, S.L., Kamata, T., Cunningham, J.A., Emsley, J., Liddington, R.C., Takada, Y., Bergelson, J.M. J. Biol. Chem. (1997) [Pubmed]
  17. Determination of the affinity and kinetic constants for the interaction between the human virus echovirus 11 and its cellular receptor, CD55. Lea, S.M., Powell, R.M., McKee, T., Evans, D.J., Brown, D., Stuart, D.I., van der Merwe, P.A. J. Biol. Chem. (1998) [Pubmed]
  18. Natural genetic recombination between co-circulating heterotypic enteroviruses. Oprisan, G., Combiescu, M., Guillot, S., Caro, V., Combiescu, A., Delpeyroux, F., Crainic, R. J. Gen. Virol. (2002) [Pubmed]
  19. Search for persistent infection with poliovirus or other enteroviruses in amyotrophic lateral sclerosis-motor neurone disease. Swanson, N.R., Fox, S.A., Mastaglia, F.L. Neuromuscul. Disord. (1995) [Pubmed]
  20. Analyses on possible heterogeneity of IDDM based on presence of islet cell cytoplasmic antibody at diagnosis. Cavender, D.E., Rabin, B.S., Dorman, J.S., Eberhardt, M.S., Laporte, R.E., Orchard, T.J., Wagener, D.K., Becker, D.J., Atchison, R.W., Drash, A.L. Autoimmunity (1989) [Pubmed]
  21. Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses. Bergelson, J.M., Chan, M., Solomon, K.R., St John, N.F., Lin, H., Finberg, R.W. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  22. Enterovirus receptors and virus replication in human leukocytes. Vuorinen, T., Vainionpää, R., Heino, J., Hyypiä, T. J. Gen. Virol. (1999) [Pubmed]
  23. Integrin alpha(v)beta3 (vitronectin receptor) is a candidate receptor for the virulent echovirus 9 strain Barty. Nelsen-Salz, B., Eggers, H.J., Zimmermann, H. J. Gen. Virol. (1999) [Pubmed]
  24. Enterovirus infection and activation of human umbilical vein endothelial cells. Saijets, S., Ylipaasto, P., Vaarala, O., Hovi, T., Roivainen, M. J. Med. Virol. (2003) [Pubmed]
  25. Experimental study of antibiotic-induced immunosuppression in mice. 1. Humoral and cell-mediated immune responsiveness related to in vivo antibiotic treatment. Voiculescu, C., Stanciu, L., Voiculescu, M., Rogoz, S., Dumitriu, I. Comp. Immunol. Microbiol. Infect. Dis. (1983) [Pubmed]
  26. Human cardiac inflammatory responses triggered by Coxsackie B viruses are mainly Toll-like receptor (TLR) 8-dependent. Triantafilou, K., Orthopoulos, G., Vakakis, E., Ahmed, M.A., Golenbock, D.T., Lepper, P.M., Triantafilou, M. Cell. Microbiol. (2005) [Pubmed]
  27. Integrin alpha 2 cytoplasmic domain deletion effects: loss of adhesive activity parallels ligand-independent recruitment into focal adhesions. Kawaguchi, S., Bergelson, J.M., Finberg, R.W., Hemler, M.E. Mol. Biol. Cell (1994) [Pubmed]
  28. Cleavage of RasGAP and phosphorylation of mitogen-activated protein kinase in the course of coxsackievirus B3 replication. Huber, M., Watson, K.A., Selinka, H.C., Carthy, C.M., Klingel, K., McManus, B.M., Kandolf, R. J. Virol. (1999) [Pubmed]
  29. Molecular classification of coxsackie A viruses on the basis of the 5'-UTR: structural and evolutionary aspects. Siafakas, N., Markoulatos, P., Stanway, G. J. Mol. Evol. (2002) [Pubmed]
  30. HLA heterogeneity of insulin-dependent diabetes mellitus at diagnosis. The Pittsburgh IDDM study. Eberhardt, M.S., Wagener, D.K., Orchard, T.J., LaPorte, R.E., Cavender, D.E., Rabin, B.S., Atchison, R.W., Kuller, L.H., Drash, A.L., Becker, D.J. Diabetes (1985) [Pubmed]
  31. Structural and functional insights into the interaction of echoviruses and decay-accelerating factor. Pettigrew, D.M., Williams, D.T., Kerrigan, D., Evans, D.J., Lea, S.M., Bhella, D. J. Biol. Chem. (2006) [Pubmed]
  32. Molecular and biological characteristics of echovirus 22, a representative of a new picornavirus group. Stanway, G., Kalkkinen, N., Roivainen, M., Ghazi, F., Khan, M., Smyth, M., Meurman, O., Hyypiä, T. J. Virol. (1994) [Pubmed]
  33. Use of modified diatomaceous earth for removal and recovery of viruses in water. Farrah, S.R., Preston, D.R., Toranzos, G.A., Girard, M., Erdos, G.A., Vasuhdivan, V. Appl. Environ. Microbiol. (1991) [Pubmed]
  34. Laboratory diagnosis and genetic analysis of an echovirus 30-associated outbreak of aseptic meningitis in Taiwan in 2001. Wang, J.R., Tsai, H.P., Huang, S.W., Kuo, P.H., Kiang, D., Liu, C.C. J. Clin. Microbiol. (2002) [Pubmed]
  35. Immunoglobulin responses to echovirus type 11 by enzyme linked immunosorbent assay: single-serum diagnosis of acute infection by specific IgM antibody. Gong, C.M., Ho, D.W., Field, P.R., Murphy, A.M. J. Virol. Methods (1984) [Pubmed]
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