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. 1995 Mar;69(3):1959–1963. doi: 10.1128/jvi.69.3.1959-1963.1995

Characterization of a live, attenuated human parainfluenza type 3 virus candidate vaccine strain.

R Ray 1, K Meyer 1, F K Newman 1, R B Belshe 1
PMCID: PMC188817  PMID: 7853542

Abstract

Characterization of a temperature-sensitive and live, attenuated human parainfluenza type 3 virus strain (cp45) grown at a permissive temperature (32 degrees C) suggested that the virus efficiently multiplies in cell lines and retains antigenic and functional properties of the envelope glycoproteins. When grown at a nonpermissive temperature (39.5 degrees C), the cp45 virus exhibited poor replication; however, shifting to a permissive temperature allowed virus growth. Although at a nonpermissive temperature virus polypeptide synthesis was significantly reduced, the hemagglutinin-neuraminidase and fusion glycoproteins were transported to cell surfaces and retained their characteristic biologic activities. Studies on mRNA synthesis from the P protein gene suggested a poor transcriptional activity of the cp45 virus at a nonpermissive temperature. Results from this study indicate that the temperature sensitivity of cp45 virus is related to altered transcriptional activity and a marked reduction in virus polypeptide synthesis.

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Selected References

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  1. Al-Ahdal M. N., Nakamura I., Flanagan T. D. Cytotoxic T-lymphocyte reactivity with individual Sendai virus glycoproteins. J Virol. 1985 Apr;54(1):53–57. doi: 10.1128/jvi.54.1.53-57.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Belshe R. B., Hissom F. K. Cold adaptation of parainfluenza virus type 3: induction of three phenotypic markers. J Med Virol. 1982;10(4):235–242. doi: 10.1002/jmv.1890100403. [DOI] [PubMed] [Google Scholar]
  3. Belshe R. B., Karron R. A., Newman F. K., Anderson E. L., Nugent S. L., Steinhoff M., Clements M. L., Wilson M. H., Hall S. L., Tierney E. L. Evaluation of a live attenuated, cold-adapted parainfluenza virus type 3 vaccine in children. J Clin Microbiol. 1992 Aug;30(8):2064–2070. doi: 10.1128/jcm.30.8.2064-2070.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Clements M. L., Belshe R. B., King J., Newman F., Westblom T. U., Tierney E. L., London W. T., Murphy B. R. Evaluation of bovine, cold-adapted human, and wild-type human parainfluenza type 3 viruses in adult volunteers and in chimpanzees. J Clin Microbiol. 1991 Jun;29(6):1175–1182. doi: 10.1128/jcm.29.6.1175-1182.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crookshanks-Newman F. K., Belshe R. B. Protection of weanling hamsters from experimental infection with wild-type parainfluenza virus type 3 (para 3) by cold-adapted mutants of para 3. J Med Virol. 1986 Feb;18(2):131–137. doi: 10.1002/jmv.1890180205. [DOI] [PubMed] [Google Scholar]
  7. Ebata S. N., Côté M. J., Kang C. Y., Dimock K. The fusion and hemagglutinin-neuraminidase glycoproteins of human parainfluenza virus 3 are both required for fusion. Virology. 1991 Jul;183(1):437–441. doi: 10.1016/0042-6822(91)90162-5. [DOI] [PubMed] [Google Scholar]
  8. Hall S. L., Sarris C. M., Tierney E. L., London W. T., Murphy B. R. A cold-adapted mutant of parainfluenza virus type 3 is attenuated and protective in chimpanzees. J Infect Dis. 1993 Apr;167(4):958–962. doi: 10.1093/infdis/167.4.958. [DOI] [PubMed] [Google Scholar]
  9. Herlocher M. L., Maassab H. F., Webster R. G. Molecular and biological changes in the cold-adapted "master strain" A/AA/6/60 (H2N2) influenza virus. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6032–6036. doi: 10.1073/pnas.90.13.6032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hu X. L., Ray R., Compans R. W. Functional interactions between the fusion protein and hemagglutinin-neuraminidase of human parainfluenza viruses. J Virol. 1992 Mar;66(3):1528–1534. doi: 10.1128/jvi.66.3.1528-1534.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kasel J. A., Frank A. L., Keitel W. A., Taber L. H., Glezen W. P. Acquisition of serum antibodies to specific viral glycoproteins of parainfluenza virus 3 in children. J Virol. 1984 Dec;52(3):828–832. doi: 10.1128/jvi.52.3.828-832.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Peeples M. E., Bratt M. A. Virion functions of RNA+ temperature-sensitive mutants of Newcastle disease virus. J Virol. 1982 May;42(2):440–446. doi: 10.1128/jvi.42.2.440-446.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Peeples M. E., Rasenas L. L., Bratt M. A. RNA synthesis by Newcastle disease virus temperature-sensitive mutants in two RNA-negative complementation groups. J Virol. 1982 Jun;42(3):996–1006. doi: 10.1128/jvi.42.3.996-1006.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Portner A., Scroggs R. A., Marx P. S., Kingsbury D. W. A temperature-sensitive mutant of Sendai virus with an altered hemagglutinin-neuraminidase polypeptide: consequences for virus assembly and cytopathology. Virology. 1975 Sep;67(1):179–187. doi: 10.1016/0042-6822(75)90415-8. [DOI] [PubMed] [Google Scholar]
  15. Randall R. E., Young D. F. Humoral and cytotoxic T cell immune responses to internal and external structural proteins of simian virus 5 induced by immunization with solid matrix-antibody-antigen complexes. J Gen Virol. 1988 Oct;69(Pt 10):2505–2516. doi: 10.1099/0022-1317-69-10-2505. [DOI] [PubMed] [Google Scholar]
  16. Ray R., Brown V. E., Compans R. W. Glycoproteins of human parainfluenza virus type 3: characterization and evaluation as a subunit vaccine. J Infect Dis. 1985 Dec;152(6):1219–1230. doi: 10.1093/infdis/152.6.1219. [DOI] [PubMed] [Google Scholar]
  17. Ray R., Compans R. W. Glycoproteins of human parainfluenza virus type 3: affinity purification, antigenic characterization and reconstitution into lipid vesicles. J Gen Virol. 1987 Feb;68(Pt 2):409–418. doi: 10.1099/0022-1317-68-2-409. [DOI] [PubMed] [Google Scholar]
  18. Ray R., Compans R. W. Monoclonal antibodies reveal extensive antigenic differences between the hemagglutinin-neuraminidase glycoproteins of human and bovine parainfluenza 3 viruses. Virology. 1986 Jan 15;148(1):232–236. doi: 10.1016/0042-6822(86)90420-4. [DOI] [PubMed] [Google Scholar]
  19. Ray R., Glaze B. J., Compans R. W. Role of individual glycoproteins of human parainfluenza virus type 3 in the induction of a protective immune response. J Virol. 1988 Mar;62(3):783–787. doi: 10.1128/jvi.62.3.783-787.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ray R., Jameel S., Manivel V., Ray R. Indian hepatitis E virus shows a major deletion in the small open reading frame. Virology. 1992 Jul;189(1):359–362. doi: 10.1016/0042-6822(92)90716-3. [DOI] [PubMed] [Google Scholar]
  21. Ren R. B., Moss E. G., Racaniello V. R. Identification of two determinants that attenuate vaccine-related type 2 poliovirus. J Virol. 1991 Mar;65(3):1377–1382. doi: 10.1128/jvi.65.3.1377-1382.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shibata S., Yamamoto-Goshima F., Maeno K., Hanaichi T., Fujita Y., Nakajima K., Imai M., Komatsu T., Sugiura S. Characterization of a temperature-sensitive influenza B virus mutant defective in neuraminidase. J Virol. 1993 Jun;67(6):3264–3273. doi: 10.1128/jvi.67.6.3264-3273.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sieg S., Muro-Cacho C., Robertson S., Huang Y., Kaplan D. Infection and immunoregulation of T lymphocytes by parainfluenza virus type 3. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6293–6297. doi: 10.1073/pnas.91.14.6293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Spriggs M. K., Collins P. L. Human parainfluenza virus type 3: messenger RNAs, polypeptide coding assignments, intergenic sequences, and genetic map. J Virol. 1986 Sep;59(3):646–654. doi: 10.1128/jvi.59.3.646-654.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Spriggs M. K., Collins P. L. Sequence analysis of the P and C protein genes of human parainfluenza virus type 3: patterns of amino acid sequence homology among paramyxovirus proteins. J Gen Virol. 1986 Dec;67(Pt 12):2705–2719. doi: 10.1099/0022-1317-67-12-2705. [DOI] [PubMed] [Google Scholar]
  26. Stokes A., Tierney E. L., Sarris C. M., Murphy B. R., Hall S. L. The complete nucleotide sequence of two cold-adapted, temperature-sensitive attenuated mutant vaccine viruses (cp12 and cp45) derived from the JS strain of human parainfluenza virus type 3 (PIV3). Virus Res. 1993 Oct;30(1):43–52. doi: 10.1016/0168-1702(93)90014-e. [DOI] [PubMed] [Google Scholar]
  27. Storey D. G., Dimock K., Kang C. Y. Structural characterization of virion proteins and genomic RNA of human parainfluenza virus 3. J Virol. 1984 Dec;52(3):761–766. doi: 10.1128/jvi.52.3.761-766.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sánchez A., Banerjee A. K. Cloning and gene assignment of mRNAs of human parainfluenza virus 3. Virology. 1985 Nov;147(1):177–186. doi: 10.1016/0042-6822(85)90237-5. [DOI] [PubMed] [Google Scholar]
  29. Thompson S. D., Portner A. Localization of functional sites on the hemagglutinin-neuraminidase glycoprotein of Sendai virus by sequence analysis of antigenic and temperature-sensitive mutants. Virology. 1987 Sep;160(1):1–8. doi: 10.1016/0042-6822(87)90037-7. [DOI] [PubMed] [Google Scholar]
  30. Tsipis J. E., Bratt M. A. Isolation and preliminary characterization of temperature-sensitive mutants of Newcastle disease virus. J Virol. 1976 Jun;18(3):848–855. doi: 10.1128/jvi.18.3.848-855.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Westrop G. D., Wareham K. A., Evans D. M., Dunn G., Minor P. D., Magrath D. I., Taffs F., Marsden S., Skinner M. A., Schild G. C. Genetic basis of attenuation of the Sabin type 3 oral poliovirus vaccine. J Virol. 1989 Mar;63(3):1338–1344. doi: 10.1128/jvi.63.3.1338-1344.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. van Wyke Coelingh K. L., Winter C., Murphy B. R. Antigenic variation in the hemagglutinin-neuraminidase protein of human parainfluenza type 3 virus. Virology. 1985 Jun;143(2):569–582. doi: 10.1016/0042-6822(85)90395-2. [DOI] [PubMed] [Google Scholar]
  33. van Wyke Coelingh K., Tierney E. L. Antigenic and functional organization of human parainfluenza virus type 3 fusion glycoprotein. J Virol. 1989 Jan;63(1):375–382. doi: 10.1128/jvi.63.1.375-382.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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