1887

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Volume 86, Issue 7

Tissue tropism of recombinant coxsackieviruses in an adult mouse model Free

Abstract

Recombinant viruses, constructed by exchanging the 5′ non-coding region (5′NCR), structural and non-structural protein coding sequences were used to investigate determinants responsible for differences between coxsackievirus A9 (CAV9) and coxsackievirus B3 (CBV3) infections in adult mice and two cell lines. Plaque assay titration of recombinant and parental viruses from different tissues from adult BALB/c mice demonstrated that the structural region of CBV3 determined tropism to the liver tissue due to receptor recognition, and the 5′NCR of CBV3 enhanced viral multiplication in the mouse pancreas. Infection with a chimeric virus, containing the structural region from CBV3 and the rest of the genome from CAV9, and the parental CBV3 strain, caused high levels of viraemia in adult mice. The ability of these viruses to infect the central nervous system suggested that neurotropism is associated with high replication levels and the presence of the CBV3 capsid proteins, which also enhanced formation of neutralizing antibodies. Moreover, the appearance of neutralizing antibodies correlated directly with the clearance of the viruses from the tissues. These results demonstrate potential pathogenicity of intraspecies recombinant coxsackieviruses, and the complexity of the genetic determinants underlying tissue tropism.

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2005-07-01
2024-04-26
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References

  1. Bergelson J. M., Mohanty J. G., Crowell R. L., St John N. F., Lublin D. M., Fingerg R. W. 1995; Coxsackievirus B3 adapted to growth in RD cells binds to decay-accelerating factor (CD55). J Virol 69:1903–1906
     [Google Scholar]
  2. Bergelson J. M., Cunningham J. A., Droguett G., Kurt-Jones E. A., Krithivas A., Hong J. S., Horwitz M. S., Crowell R. L., Finberg R. W. 1997; Isolation of common receptor for coxsackie B viruses and adenovirus 2 and 5. Science 275:1320–1323 [CrossRef]
     [Google Scholar]
  3. Bergelson J. M., Krithivas A., Celi L., Droguett G., Horwitz M. S., Wickham T., Crowell R. L., Finberg R. W. 1998; The murine CAR homolog is a receptor for coxsackie B viruses and adenoviruses. J Virol 72:415–419
     [Google Scholar]
  4. Blaschuk K. L., Guerin C., Holland P. C. 1997; Myoblast α v β 3 integrin levels are controlled by transcriptional regulation of expression of the β 3 subunit and down-regulation of β 3 subunit expression is required for skeletal muscle cell differentiation. Dev Biol 184:266–277 [CrossRef]
     [Google Scholar]
  5. Bradrick S. S., Lieben E. A., Carden B. M., Romero J. R. 2001; A predicted secondary structural domain within the internal ribosome entry site of echovirus 12 mediates a cell-type-specific block to viral replication. J Virol 75:6472–6481 [CrossRef]
     [Google Scholar]
  6. Caggana M., Chan P., Ramsingh A. 1993; Identification of a single amino acid residue in the capsid protein VP1 of coxsackievirus B4 that determines the virulent phenotype. J Virol 67:4797–4803
     [Google Scholar]
  7. Cameron-Wilson C. L., Pandolfino Y. A., Zhang H. Y., Pozzeto B., Archard L. C. 1998; Nucleotide sequence of an attenuated mutant of coxsackievirus B3 compared with the cardiovirulent wildtype: assessment of candidate mutations by analysis of a revertant to cardiovirulence. Clin Diagn Virol 9:99–105 [CrossRef]
     [Google Scholar]
  8. Chang K. H., Auvinen P., Hyypiä T., Stanway G. 1989; The nucleotide sequence of coxsackievirus A9; implications for receptor binding and enterovirus classification. J Gen Virol 70:3269–3280 [CrossRef]
     [Google Scholar]
  9. Dalldorf G., Melnick J. L. 1965; Coxsackieviruses. Viral and Rickettsial Infections of Man . pp  472–512 Edited by Horsfall F. L., Tamm I. Philadelphia: Lippincott;
  10. Dunn J. J., Chapman N. M., Tracy S., Romero J. R. 2000; Genomic determinants of cardiovirulence in coxsackievirus B3 clinical isolates: localization to the 5′ nontranslated region. J Virol 74:4787–4794 [CrossRef]
     [Google Scholar]
  11. Dunn J. J., Bradrick S. S., Chapman N. M., Tracy S. M., Romero J. R. 2003; The stem loop II within the 5′ nontranslated region of clinical coxsackievirus B3 genomes determines cardiovirulence phenotype in a murine model. J Infect Dis 187:1552–1561 [CrossRef]
     [Google Scholar]
  12. Evans J. D., Almond J. W. 1998; Cell receptors for picornaviruses as determinants of cell tropism and pathogenesis. Trends Microbiol 6:198–202 [CrossRef]
     [Google Scholar]
  13. Evans D. M. A., Dunn G., Minor P. D., Schild G. C., Cann A. J., Stanway G., Almond J. W., Currey K., Maizel J. V. Jr 1985; Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. Nature 314:548–550 [CrossRef]
     [Google Scholar]
  14. Feuer R., Mena I., Pagarigan R. R., Harkins S., Hassett D. E., Whitton J. L. 2003; Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. Am J Pathol 163:1379–1393 [CrossRef]
     [Google Scholar]
  15. Geller T. J., Condie D. 1995; A case of protracted coxsackievirus meningoencephalitis in a marginally immunodeficient child treated successfully with intravenous immunoglobulin. J Neurol Sci 129:131–133
     [Google Scholar]
  16. Grist N. R., Bell E. J., Assaad F. 1978; Enteroviruses in human disease. Prog Med Virol 24:114–157
     [Google Scholar]
  17. Gromeier M., Bossert B., Arita M., Nomoto A., Wimmer E. 1999; Dual stem loops within the poliovirus internal ribosomal entry site control neurovirulence. J Virol 73:958–964
     [Google Scholar]
  18. Harvala H., Kalimo H., Dahllund L., Santti J., Hughes P., Hyypiä T., Stanway G. 2002; Mapping of tissue tropism determinants in coxsackievirus genomes. J Gen Virol 83:1697–1706
     [Google Scholar]
  19. Harvala H., Kalimo H., Stanway G., Hyypiä T. 2003; Pathogenesis of coxsackievirus A9 in mice: role of the viral arginine-glycine-aspartic acid motif. J Gen Virol 84:2375–2379 [CrossRef]
     [Google Scholar]
  20. Hertel N. T., Pedersen F. K., Heilmann C. 1989; Coxsackie B3 virus encephalitis in a patient with agammaglobulinaemia. Eur J Pediatr 148:642–643 [CrossRef]
     [Google Scholar]
  21. Hodes D. S., Espinoza D. V. 1981; Temperature sensitivity of isolates of echovirus type II causing chronic meningoencephalitis in an agammaglobulinemic patient. J Infect Dis 144:377 [CrossRef]
     [Google Scholar]
  22. Hughes P., Horsnell C., Hyypiä T., Stanway G. 1995; The coxsackievirus A9 RGD motif is not essential for virus viability. J Virol 69:8035–8040
     [Google Scholar]
  23. Hughes S. A., Thaker H. M., Racaniello V. R. 2003; Transgenic mouse model for echovirus myocarditis and paralysis. Proc Natl Acad Sci U S A 100:15906–15911 [CrossRef]
     [Google Scholar]
  24. Hyöty H., Taylor K. W. 2002; The role of viruses in human diabetes. Diabetologia 45:1353–1361 [CrossRef]
     [Google Scholar]
  25. Hyypiä T., Kallajoki M., Maaronen M., Stanway G., Kandolf R., Auvinen P., Kalimo H. 1993; Pathogenetic differences between coxsackie A and B virus infections in newborn mice. Virus Res 27:71–78 [CrossRef]
     [Google Scholar]
  26. Hyypiä T., Hovi T., Knowles N. J., Stanway G. 1997; Classification of enteroviruses based on molecular and biological properties. J Gen Virol 78:1–11
     [Google Scholar]
  27. Jongen P. J., Heessen F. W., ter Laak H. J., Galama J. M., Gabreels F. J. 1994; Coxsackie B1 virus-induced murine myositis: relationship of disease severity to virus dose and antiviral antibody response. Neuromuscul Disord 4:17–23 [CrossRef]
     [Google Scholar]
  28. Kandolf R., Hofschneider P. H. 1985; Molecular cloning of the genome of a cardiotropic coxsackie B3 virus: full-length reverse-transcribed recombinant cDNA generates infectious virus in mammalian cells. Proc Natl Acad Sci U S A 82:4818–4822 [CrossRef]
     [Google Scholar]
  29. Kang Y., Chatterjee N. K., Nodwell M. J., Yoon J. W. 1994; Complete nucleotide sequence of a strain of coxsackie B4 virus of human origin that induces diabetes in mice and its comparison with nondiabetogenic coxsackie B4 JBV strain. J Med Virol 44:353–361 [CrossRef]
     [Google Scholar]
  30. Kimura E., Maeda Y., Arima T., Nishida Y., Yamashita S., Hara A., Uyama E., Mita S., Uchino M. 2001; Efficient repetitive gene delivery to skeletal muscle using recombinant adenovirus vector containing the coxsackievirus and adenovirus receptor cDNA. Gene Ther 8:20–27 [CrossRef]
     [Google Scholar]
  31. Klingel K., Stephan S., Sauter M., Zell R., McManus B. M., Bultmann B., Kandolf R. 1996; Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets. J Virol 70:8888–8895
     [Google Scholar]
  32. Klump W. M., Bergmann I., Muller B. C., Ameis D., Kandolf R. 1990; Complete nucleotide sequence of infectious coxsackievirus B3 cDNA: two initial 5′ uridine residues are regained during plus-strand RNA synthesis. J Virol 64:1573–1583
     [Google Scholar]
  33. Knowlton K. U., Jeon E. S., Berkley N., Wessely R., Huber S. 1996; A mutation in the puff region of VP2 attenuates the myocarditic phenotype of an infectious cDNA of the Woodruff variant of coxsackievirus B3. J Virol 70:7811–7818
     [Google Scholar]
  34. Mena I., Perry C. M., Harkins S., Robriquez F., Gebhard J., Whitton L. J. 1999; The role of B lymphocytes in coxsackievirus B3 infection. Am J Pathol 155:1205–1215 [CrossRef]
     [Google Scholar]
  35. Mena I., Fischer C., Gebhard J. R., Perry C. M., Harkins S., Whitton J. L. 2000; Coxsackievirus infection of the pancreas: evaluation of receptor expression, pathogenesis, and immunopathology. Virology 271:276–288 [CrossRef]
     [Google Scholar]
  36. Menko A. S., Boettiger D. 1987; Occupation of the extracellular matrix receptor, integrin, is a control point myogenic differentiation. Cell 51:51–57 [CrossRef]
     [Google Scholar]
  37. Minor P. D. 1992; The molecular biology of poliovaccines. J Gen Virol 73:3065–3077 [CrossRef]
     [Google Scholar]
  38. Nalbantoglu J., Pari G., Karpati G., Holland P. C. 1999; Expression of the primary coxsackie and adenovirus receptor is downregulated during skeletal muscle maturation and limits the efficacy of adenovirus-mediated gene delivery to muscle cells. Hum Gene Ther 10:1009–1019 [CrossRef]
     [Google Scholar]
  39. Pulli T., Koskimies P., Hyypiä T. 1995; Molecular comparison of coxsackie A virus serotypes. Virology 212:30–38 [CrossRef]
     [Google Scholar]
  40. Ramsingh A. I., Collins D. N. 1995; A point mutation in the VP4 coding sequence of coxsackievirus B4 influences virulence. J Virol 69:7278–7281
     [Google Scholar]
  41. Ren R. B., Moss E. G., Racaniello V. R. 1991; Identification of two determinants that attenuate vaccine-related type 2 poliovirus. J Virol 65:1377–1382
     [Google Scholar]
  42. Rinehart J. E., Gómez R. M., Roos R. P. 1997; Molecular determinants for virulence in coxsackievirus B1 infection. J Virol 71:3986–3991
     [Google Scholar]
  43. Roivainen M., Hyypiä T., Piirainen L., Kalkkinen N., Stanway G., Hovi T. 1991; RGD-dependent entry of coxsackievirus A9 into host cell and its bypass after cleavage of VP1 protein by intestinal proteases. J Virol 65:4735–4740
     [Google Scholar]
  44. Roivainen M., Piirainen L., Hovi T., Virtanen I., Riikonen T., Heino J., Hyypiä T. 1994; Entry of coxsackievirus A9 into host cells: specific interactions with α v β 3 integrin, the vitronectin receptor. Virology 203:357–365 [CrossRef]
     [Google Scholar]
  45. Roivainen M., Piirainen L., Hovi T. 1996; Efficient RGD-independent entry process of coxsackievirus A9. Arch Virol 141:1909–1919 [CrossRef]
     [Google Scholar]
  46. Roivainen M., Knip M., Hyöty H., Kulmala P., Hiltunen M., Vahasalo P., Hovi T., Åkerblom H. K. 1998; Several different enterovirus serotypes can be associated with prediabetic autoimmune episodes and onset of overt IDDM. Childhood Diabetes in Finland (DiMe) Study Group. J Med Virol 56:74–78 [CrossRef]
     [Google Scholar]
  47. Spiller O. B., Goodfellow I. G., Evans D. J., Almond J. W., Morgan B. P. 2002; Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind the rodent analogues of DAF. J Infect Dis 181:340–343
     [Google Scholar]
  48. Stanway G. 1990; Structure, function and evolution of picornaviruses. J Gen Virol 71:2483–2501 [CrossRef]
     [Google Scholar]
  49. Svitkin Y. V., Cammack N., Minor P. D., Almond J. 1990; Translation deficiency of the Sabin type 3 poliovirus genome: association with an attenuating mutation C472→U. Virology 175:103–109 [CrossRef]
     [Google Scholar]
  50. Tam P. E., Weber-Sanders M. L., Messner R. P. 2003; Multiple viral determinants mediate myopathogenicity in coxsackievirus B1-induced chronic inflammatory myopathy. J Virol 77:11849–11854 [CrossRef]
     [Google Scholar]
  51. Tracy S., Höfling K., Pirruccello S., Lane P. H., Reyna S. M., Gauntt C. J. 2000; Group B coxsackievirus myocarditis and pancreatitis: connection between viral virulence phenotypes in mice. J Med Virol 62:70–81 [CrossRef]
     [Google Scholar]
  52. Triantafilou M., Triantafilou K., Wilson K. M., Takada Y., Fernandez N. 2000; High affinity interactions of coxsackievirus A9 with integrin α v β 3 (CD51/61) require the CYDMKTTC sequence of β 3, but do not require the RGD sequence of the CAV-9 VP1 protein. Human Immunol 61:453–459 [CrossRef]
     [Google Scholar]
  53. Tu Z., Chapman N. M., Hufnagel G., Tracy S., Romero J. R., Barry W. H., Zhao L., Currey K., Shapiro B. 1995; The cardiovirulent phenotype of coxsackievirus B3 is determined at a single site in the genomic 5′ nontranslated region. J Virol 69:4607–4618
     [Google Scholar]
  54. Vuorinen T., Kallajoki M., Hyypiä T., Vainionpää R. 1989; Coxsackievirus B3-induced acute pancreatitis: analysis of histopathological and viral parameters in a mouse model. Br J Exp Pathol 70:395–403
     [Google Scholar]
  55. Vuorinen T., Vainionpää R., Kettinen H., Hyypiä T. 1994; Coxsackievirus B3 infection in human leukocytes and lymphoid cell lines. Blood 84:823–829
     [Google Scholar]
  56. Waris M., Ziegler T., Kivivirta M., Ruuskanen O. 1990; Rapid detection of respiratory syncytial virus and influenza A virus in cell cultures by immunoperoxidase staining with monoclonal antibodies. J Clin Microbiol 28:1159–1162
     [Google Scholar]
  57. Wilfert C. M., Buckley R. H., Mohanakumar T. 8 other authors 1977; Persistent and fatal central-nervous-system ECHOvirus infections in patients with agammaglobulinemia. N Engl J Med 296:1485–1489 [CrossRef]
     [Google Scholar]
  58. Williams C. H., Kajander T., Hyypiä T., Jackson T., Sheppard D., Stanway G. 2004; Integrin α v β 6 is an RGD-dependent receptor for coxsackievirus A9. J Virol 78:6967–6973 [CrossRef]
     [Google Scholar]
  59. Yin H., Berg A. K., Westman J., Hellerstrom C., Frisk G. 2002; Complete nucleotide sequence of a Coxsackievirus B-4 strain capable of establishing persistent infection in human pancreatic islet cells: effects on insulin release, proinsulin synthesis, and cell morphology. J Med Virol 68:544–557 [CrossRef]
     [Google Scholar]
  60. Ylipaasto P., Klingel K., Lindberg A. M., Otonkoski T., Kandolf R., Hovi T., Roivainen M. 2004; Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells. Diabetologia 47:225–239 [CrossRef]
     [Google Scholar]
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Tissue tropism of recombinant coxsackieviruses in an adult mouse model
J. Gen. Virol. 86, 1897 (2005); https://doi.org/10.1099/vir.0.80603-0
/content/journal/jgv/10.1099/vir.0.80603-0
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