Attenuation of wild-type yellow fever virus by passage in HeLa cells

Alan Barrett, T. P. Monath, C. B. Cropp, J. A. Adkins, T. N. Ledger, E. A. Gould, J. J. Schlesinger, R. M. Kinney, D. W. Trent

Research output: Contribution to journalArticle

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Abstract

During the 1960s three different research groups reported that passage of wild-type yellow fever (YF) virus [strain Asibi (YF-Asibi)] in HeLa cells resulted in attenuation of the virus for monkeys so that the virus no longer caused viscerotropic disease. We have repeated and extended this observation to analyse the process of attenuation of YF virus during cell culture passage. A large plaque (LP) variant of YF-Asibi virus became attenuated for both monkeys and mice following six serial subcultures in HeLa cells (YF-Asibi-LP HeLa p6). Thus, attenuation was probably due to a genetic change in the virus population rather than to selective enrichment of a pre-existing variant of YF-Asibi-LP virus. No evidence was obtained to implicate defective interfering particles in the attenuation process. Comparison of the YF-Asibi-LP viruses before and after passage in HeLa cells, using a panel of envelope protein-reactive monoclonal antibodies (MAbs), showed that MAbs which specifically neutralize YF-Asibi-LP virus, and not YF 17D-204 vaccine virus, also neutralized YF-Asibi-LP HeLa p6. This indicated that the epitopes involved in the biological process of neutralization were not altered during attenuation. However, two MAbs that recognize envelope protein epitopes did distinguish between HeLa- and non-HeLa-passaged YF-Asibi-LP virus. One of these (MAb 117) which is YF wild-type-specific, recognized YF-Asibi-LP virus but not YF-Asibi-LP HeLa p6 virus, whereas the other (MAb 411), which is YF vaccine-specific, recognized YF-Asibi-LP HeLa p6 virus but not YF-Asibi-LP virus. These results suggest that antigenic changes in the viral envelope protein may determine the relative virulence or attenuation of YF virus.

Original languageEnglish (US)
Pages (from-to)2301-2306
Number of pages6
JournalJournal of General Virology
Volume71
Issue number10
StatePublished - 1990
Externally publishedYes

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Yellow fever virus
Yellow Fever
HeLa Cells
Viruses
Monoclonal Antibodies
Haplorhini
Epitopes
Yellow Fever Vaccine
Viral Envelope Proteins
Defective Viruses
Biological Phenomena
Virulence
Proteins
Vaccines
Cell Culture Techniques

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Barrett, A., Monath, T. P., Cropp, C. B., Adkins, J. A., Ledger, T. N., Gould, E. A., ... Trent, D. W. (1990). Attenuation of wild-type yellow fever virus by passage in HeLa cells. Journal of General Virology, 71(10), 2301-2306.

Attenuation of wild-type yellow fever virus by passage in HeLa cells. / Barrett, Alan; Monath, T. P.; Cropp, C. B.; Adkins, J. A.; Ledger, T. N.; Gould, E. A.; Schlesinger, J. J.; Kinney, R. M.; Trent, D. W.

In: Journal of General Virology, Vol. 71, No. 10, 1990, p. 2301-2306.

Research output: Contribution to journalArticle

Barrett, A, Monath, TP, Cropp, CB, Adkins, JA, Ledger, TN, Gould, EA, Schlesinger, JJ, Kinney, RM & Trent, DW 1990, 'Attenuation of wild-type yellow fever virus by passage in HeLa cells', Journal of General Virology, vol. 71, no. 10, pp. 2301-2306.
Barrett A, Monath TP, Cropp CB, Adkins JA, Ledger TN, Gould EA et al. Attenuation of wild-type yellow fever virus by passage in HeLa cells. Journal of General Virology. 1990;71(10):2301-2306.
Barrett, Alan ; Monath, T. P. ; Cropp, C. B. ; Adkins, J. A. ; Ledger, T. N. ; Gould, E. A. ; Schlesinger, J. J. ; Kinney, R. M. ; Trent, D. W. / Attenuation of wild-type yellow fever virus by passage in HeLa cells. In: Journal of General Virology. 1990 ; Vol. 71, No. 10. pp. 2301-2306.
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abstract = "During the 1960s three different research groups reported that passage of wild-type yellow fever (YF) virus [strain Asibi (YF-Asibi)] in HeLa cells resulted in attenuation of the virus for monkeys so that the virus no longer caused viscerotropic disease. We have repeated and extended this observation to analyse the process of attenuation of YF virus during cell culture passage. A large plaque (LP) variant of YF-Asibi virus became attenuated for both monkeys and mice following six serial subcultures in HeLa cells (YF-Asibi-LP HeLa p6). Thus, attenuation was probably due to a genetic change in the virus population rather than to selective enrichment of a pre-existing variant of YF-Asibi-LP virus. No evidence was obtained to implicate defective interfering particles in the attenuation process. Comparison of the YF-Asibi-LP viruses before and after passage in HeLa cells, using a panel of envelope protein-reactive monoclonal antibodies (MAbs), showed that MAbs which specifically neutralize YF-Asibi-LP virus, and not YF 17D-204 vaccine virus, also neutralized YF-Asibi-LP HeLa p6. This indicated that the epitopes involved in the biological process of neutralization were not altered during attenuation. However, two MAbs that recognize envelope protein epitopes did distinguish between HeLa- and non-HeLa-passaged YF-Asibi-LP virus. One of these (MAb 117) which is YF wild-type-specific, recognized YF-Asibi-LP virus but not YF-Asibi-LP HeLa p6 virus, whereas the other (MAb 411), which is YF vaccine-specific, recognized YF-Asibi-LP HeLa p6 virus but not YF-Asibi-LP virus. These results suggest that antigenic changes in the viral envelope protein may determine the relative virulence or attenuation of YF virus.",
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AU - Adkins, J. A.

AU - Ledger, T. N.

AU - Gould, E. A.

AU - Schlesinger, J. J.

AU - Kinney, R. M.

AU - Trent, D. W.

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