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. 1996 Nov;70(11):8175–8181. doi: 10.1128/jvi.70.11.8175-8181.1996

Bovine viral diarrhea virus: characterization of a cytopathogenic defective interfering particle with two internal deletions.

H Kupfermann 1, H J Thiel 1, E J Dubovi 1, G Meyers 1
PMCID: PMC190898  PMID: 8892949

Abstract

Molecular characterization of bovine viral diarrhea virus pair 13 revealed that isolate CP13 is composed of a cytopathogenic (cp) defective interfering particle (DI13) and a noncytopathogenic (noncp) helper virus. The DI13 genome possesses two internal deletions of 1,611 and 3,102 nucleotides. Except for a small fragment of the gene coding for glycoprotein E1, all structural protein genes are deleted together with most of the Npro gene, the region coding for nonstructural proteins p7 and NS2. While the amino terminus of NS3 seems to be strictly conserved for all other cp bovine viral diarrhea viruses, NS3 of DI13 is amino-terminally truncated and fused to 23 amino acids derived from Npro and E1. Characterization of the DI-helper virus system revealed a striking discrepancy between RNA production and generation of infectious viruses.

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Selected References

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  1. Baker J. C. Bovine viral diarrhea virus: a review. J Am Vet Med Assoc. 1987 Jun 1;190(11):1449–1458. [PubMed] [Google Scholar]
  2. Barrett A. D., Dimmock N. J. Defective interfering viruses and infections of animals. Curr Top Microbiol Immunol. 1986;128:55–84. doi: 10.1007/978-3-642-71272-2_2. [DOI] [PubMed] [Google Scholar]
  3. Bartenschlager R., Ahlborn-Laake L., Mous J., Jacobsen H. Kinetic and structural analyses of hepatitis C virus polyprotein processing. J Virol. 1994 Aug;68(8):5045–5055. doi: 10.1128/jvi.68.8.5045-5055.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bartenschlager R., Lohmann V., Wilkinson T., Koch J. O. Complex formation between the NS3 serine-type proteinase of the hepatitis C virus and NS4A and its importance for polyprotein maturation. J Virol. 1995 Dec;69(12):7519–7528. doi: 10.1128/jvi.69.12.7519-7528.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bolin S. R., McClurkin A. W., Cutlip R. C., Coria M. F. Severe clinical disease induced in cattle persistently infected with noncytopathic bovine viral diarrhea virus by superinfection with cytopathic bovine viral diarrhea virus. Am J Vet Res. 1985 Mar;46(3):573–576. [PubMed] [Google Scholar]
  6. Brownlie J., Clarke M. C., Howard C. J. Experimental production of fatal mucosal disease in cattle. Vet Rec. 1984 Jun 2;114(22):535–536. doi: 10.1136/vr.114.22.535. [DOI] [PubMed] [Google Scholar]
  7. Bruton C. J., Kennedy S. I. Defective-interfering particles of Semliki Forest Virus: structural differences between standard virus and defective-interfering particles. J Gen Virol. 1976 Jun;31(3):383–395. doi: 10.1099/0022-1317-31-3-383. [DOI] [PubMed] [Google Scholar]
  8. Cole C. N. Defective interfering (di) particles of poliovirus. Prog Med Virol. 1975;20:180–207. [PubMed] [Google Scholar]
  9. Colett M. S., Larson R., Gold C., Strick D., Anderson D. K., Purchio A. F. Molecular cloning and nucleotide sequence of the pestivirus bovine viral diarrhea virus. Virology. 1988 Jul;165(1):191–199. doi: 10.1016/0042-6822(88)90672-1. [DOI] [PubMed] [Google Scholar]
  10. Collett M. S., Larson R., Belzer S. K., Retzel E. Proteins encoded by bovine viral diarrhea virus: the genomic organization of a pestivirus. Virology. 1988 Jul;165(1):200–208. doi: 10.1016/0042-6822(88)90673-3. [DOI] [PubMed] [Google Scholar]
  11. Collett M. S., Wiskerchen M., Welniak E., Belzer S. K. Bovine viral diarrhea virus genomic organization. Arch Virol Suppl. 1991;3:19–27. doi: 10.1007/978-3-7091-9153-8_3. [DOI] [PubMed] [Google Scholar]
  12. Corapi W. V., Donis R. O., Dubovi E. J. Monoclonal antibody analyses of cytopathic and noncytopathic viruses from fatal bovine viral diarrhea virus infections. J Virol. 1988 Aug;62(8):2823–2827. doi: 10.1128/jvi.62.8.2823-2827.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Deng R., Brock K. V. Molecular cloning and nucleotide sequence of a pestivirus genome, noncytopathic bovine viral diarrhea virus strain SD-1. Virology. 1992 Dec;191(2):867–869. doi: 10.1016/0042-6822(92)90262-n. [DOI] [PubMed] [Google Scholar]
  14. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Elbers K., Tautz N., Becher P., Stoll D., Rümenapf T., Thiel H. J. Processing in the pestivirus E2-NS2 region: identification of proteins p7 and E2p7. J Virol. 1996 Jun;70(6):4131–4135. doi: 10.1128/jvi.70.6.4131-4135.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Failla C., Tomei L., De Francesco R. An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A. J Virol. 1995 Mar;69(3):1769–1777. doi: 10.1128/jvi.69.3.1769-1777.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fuerst T. R., Niles E. G., Studier F. W., Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122–8126. doi: 10.1073/pnas.83.21.8122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Greiser-Wilke I., Dittmar K. E., Liess B., Moennig V. Heterogeneous expression of the non-structural protein p80/p125 in cells infected with different pestiviruses. J Gen Virol. 1992 Jan;73(Pt 1):47–52. doi: 10.1099/0022-1317-73-1-47. [DOI] [PubMed] [Google Scholar]
  19. Henikoff S. Unidirectional digestion with exonuclease III in DNA sequence analysis. Methods Enzymol. 1987;155:156–165. doi: 10.1016/0076-6879(87)55014-5. [DOI] [PubMed] [Google Scholar]
  20. Huang A. S., Baltimore D. Defective viral particles and viral disease processes. Nature. 1970 Apr 25;226(5243):325–327. doi: 10.1038/226325a0. [DOI] [PubMed] [Google Scholar]
  21. Johnston R. E., Tovell D. R., Brown D. T., Faulkner P. Interfering passages of Sindbis virus: concomitant appearance of interference, morphological variants, and trucated viral RNA. J Virol. 1975 Oct;16(4):951–958. doi: 10.1128/jvi.16.4.951-958.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kennedy S. I., Bruton C. J., Weiss B., Schlesinger S. Defective interfering passages of Sindbis virus: nature of the defective virion RNA. J Virol. 1976 Sep;19(3):1034–1043. doi: 10.1128/jvi.19.3.1034-1043.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kessler S. W. Use of protein A-bearing staphylococci for the immunoprecipitation and isolation of antigens from cells. Methods Enzymol. 1981;73(Pt B):442–459. doi: 10.1016/0076-6879(81)73084-2. [DOI] [PubMed] [Google Scholar]
  24. Khan S. R., Lazzarini R. A. The relationship between autointerference and the replication of defective interfering particle. Virology. 1977 Mar;77(1):189–201. doi: 10.1016/0042-6822(77)90417-2. [DOI] [PubMed] [Google Scholar]
  25. Kirkegaard K., Baltimore D. The mechanism of RNA recombination in poliovirus. Cell. 1986 Nov 7;47(3):433–443. doi: 10.1016/0092-8674(86)90600-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kunkel T. A., Roberts J. D., Zakour R. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987;154:367–382. doi: 10.1016/0076-6879(87)54085-x. [DOI] [PubMed] [Google Scholar]
  27. Lazzarini R. A., Keene J. D., Schubert M. The origins of defective interfering particles of the negative-strand RNA viruses. Cell. 1981 Oct;26(2 Pt 2):145–154. doi: 10.1016/0092-8674(81)90298-1. [DOI] [PubMed] [Google Scholar]
  28. McClurkin A. W., Bolin S. R., Coria M. F. Isolation of cytopathic and noncytopathic bovine viral diarrhea virus from the spleen of cattle acutely and chronically affected with bovine viral diarrhea. J Am Vet Med Assoc. 1985 Mar 15;186(6):568–569. [PubMed] [Google Scholar]
  29. Meyers G., Rümenapf T., Thiel H. J. Molecular cloning and nucleotide sequence of the genome of hog cholera virus. Virology. 1989 Aug;171(2):555–567. doi: 10.1016/0042-6822(89)90625-9. [DOI] [PubMed] [Google Scholar]
  30. Meyers G., Rümenapf T., Thiel H. J. Ubiquitin in a togavirus. Nature. 1989 Oct 12;341(6242):491–491. doi: 10.1038/341491a0. [DOI] [PubMed] [Google Scholar]
  31. Meyers G., Tautz N., Dubovi E. J., Thiel H. J. Viral cytopathogenicity correlated with integration of ubiquitin-coding sequences. Virology. 1991 Feb;180(2):602–616. doi: 10.1016/0042-6822(91)90074-L. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Meyers G., Tautz N., Stark R., Brownlie J., Dubovi E. J., Collett M. S., Thiel H. J. Rearrangement of viral sequences in cytopathogenic pestiviruses. Virology. 1992 Nov;191(1):368–386. doi: 10.1016/0042-6822(92)90199-Y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Meyers G., Thiel H. J. Cytopathogenicity of classical swine fever virus caused by defective interfering particles. J Virol. 1995 Jun;69(6):3683–3689. doi: 10.1128/jvi.69.6.3683-3689.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Moormann R. J., Warmerdam P. A., van der Meer B., Schaaper W. M., Wensvoort G., Hulst M. M. Molecular cloning and nucleotide sequence of hog cholera virus strain Brescia and mapping of the genomic region encoding envelope protein E1. Virology. 1990 Jul;177(1):184–198. doi: 10.1016/0042-6822(90)90472-4. [DOI] [PubMed] [Google Scholar]
  35. Perrault J. Origin and replication of defective interfering particles. Curr Top Microbiol Immunol. 1981;93:151–207. doi: 10.1007/978-3-642-68123-3_7. [DOI] [PubMed] [Google Scholar]
  36. Pettersson R. F. 5'-Terminal nucleotide sequence of Semliki forest virus 18S defective interfering RNA is heterogeneous and different from the genomic 42S RNA. Proc Natl Acad Sci U S A. 1981 Jan;78(1):115–119. doi: 10.1073/pnas.78.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pocock D. H., Howard C. J., Clarke M. C., Brownlie J. Variation in the intracellular polypeptide profiles from different isolates of bovine virus diarrhoea virus. Arch Virol. 1987;94(1-2):43–53. doi: 10.1007/BF01313724. [DOI] [PubMed] [Google Scholar]
  38. Purchio A. F., Larson R., Collett M. S. Characterization of bovine viral diarrhea virus proteins. J Virol. 1984 May;50(2):666–669. doi: 10.1128/jvi.50.2.666-669.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Purchio A. F., Larson R., Collett M. S. Characterization of virus-specific RNA synthesized in bovine cells infected with bovine viral diarrhea virus. J Virol. 1983 Oct;48(1):320–324. doi: 10.1128/jvi.48.1.320-324.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Qi F., Ridpath J. F., Lewis T., Bolin S. R., Berry E. S. Analysis of the bovine viral diarrhea virus genome for possible cellular insertions. Virology. 1992 Jul;189(1):285–292. doi: 10.1016/0042-6822(92)90704-s. [DOI] [PubMed] [Google Scholar]
  41. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  42. Roux L., Simon A. E., Holland J. J. Effects of defective interfering viruses on virus replication and pathogenesis in vitro and in vivo. Adv Virus Res. 1991;40:181–211. doi: 10.1016/S0065-3527(08)60279-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Rümenapf T., Meyers G., Stark R., Thiel H. J. Hog cholera virus--characterization of specific antiserum and identification of cDNA clones. Virology. 1989 Jul;171(1):18–27. doi: 10.1016/0042-6822(89)90506-0. [DOI] [PubMed] [Google Scholar]
  44. Rümenapf T., Unger G., Strauss J. H., Thiel H. J. Processing of the envelope glycoproteins of pestiviruses. J Virol. 1993 Jun;67(6):3288–3294. doi: 10.1128/jvi.67.6.3288-3294.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Schlesinger S., Weiss B., Dohner D. Defective particles in alphavirus infections. Med Biol. 1975 Oct;53(5):372–379. [PubMed] [Google Scholar]
  47. Stark R., Meyers G., Rümenapf T., Thiel H. J. Processing of pestivirus polyprotein: cleavage site between autoprotease and nucleocapsid protein of classical swine fever virus. J Virol. 1993 Dec;67(12):7088–7095. doi: 10.1128/jvi.67.12.7088-7095.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Tautz N., Meyers G., Thiel H. J. Processing of poly-ubiquitin in the polyprotein of an RNA virus. Virology. 1993 Nov;197(1):74–85. doi: 10.1006/viro.1993.1568. [DOI] [PubMed] [Google Scholar]
  49. Tautz N., Thiel H. J., Dubovi E. J., Meyers G. Pathogenesis of mucosal disease: a cytopathogenic pestivirus generated by an internal deletion. J Virol. 1994 May;68(5):3289–3297. doi: 10.1128/jvi.68.5.3289-3297.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Thiel H. J., Stark R., Weiland E., Rümenapf T., Meyers G. Hog cholera virus: molecular composition of virions from a pestivirus. J Virol. 1991 Sep;65(9):4705–4712. doi: 10.1128/jvi.65.9.4705-4712.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Volenec F. J., Sheffy B. E., Baker J. A. Immunobiologic hetertypic activity associated with viral and soluble components of bovine virus diarrhea virus. Arch Gesamte Virusforsch. 1972;36(3):275–283. doi: 10.1007/BF01249858. [DOI] [PubMed] [Google Scholar]
  52. Wiskerchen M., Belzer S. K., Collett M. S. Pestivirus gene expression: the first protein product of the bovine viral diarrhea virus large open reading frame, p20, possesses proteolytic activity. J Virol. 1991 Aug;65(8):4508–4514. doi: 10.1128/jvi.65.8.4508-4514.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Wiskerchen M., Collett M. S. Pestivirus gene expression: protein p80 of bovine viral diarrhea virus is a proteinase involved in polyprotein processing. Virology. 1991 Sep;184(1):341–350. doi: 10.1016/0042-6822(91)90850-b. [DOI] [PubMed] [Google Scholar]
  54. van der Werf S., Bradley J., Wimmer E., Studier F. W., Dunn J. J. Synthesis of infectious poliovirus RNA by purified T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2330–2334. doi: 10.1073/pnas.83.8.2330. [DOI] [PMC free article] [PubMed] [Google Scholar]

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