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Molecular and biological changes associated with HeLa cell attenuation of wild-type yellow fever virus

L M Dunster1, H Wang, K D Ryman

  • 1WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Kenya Medical Research Institute, Nairobi, Kenya.

Virology
|September 25, 1999
PubMed

Insights

Passaging yellow fever virus (YF) in HeLa cells can attenuate its virulence in animal models and reduce mosquito transmission. However, not all YF virus strains are attenuated by this method, suggesting strain-specific responses.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Yellow fever virus (YF) is a mosquito-borne flavivirus causing significant global health concerns.
  • Attenuating YF virus is crucial for vaccine development and controlling outbreaks.
  • Previous studies have explored various methods for YF virus attenuation.

Purpose of the Study:

  • To investigate the effect of HeLa cell passage on the attenuation of different yellow fever virus strains.
  • To identify viral changes associated with attenuation and loss of mosquito competence.
  • To explore the role of specific viral mutations and epitope changes in the attenuation process.

Main Methods:

  • Passaging wild-type and vaccine strains of yellow fever virus (YF) in HeLa cells.
  • Assessing viral attenuation in monkeys and newborn mice.
  • Evaluating mosquito competence after HeLa cell passage.
  • Analyzing antigenic and biological properties, including envelope protein epitopes.
  • Sequencing the viral genome to identify nucleotide and amino acid substitutions.

Main Results:

  • Six passages in HeLa cells attenuated YF virus strains Asibi and French viscerotropic virus for monkeys and mice, and reduced mosquito competence.
  • HeLa cell passage did not attenuate YF virus strains Dakar 1279 and French neurotropic vaccine virus.
  • Attenuation was associated with changes in viral antigenic properties and acquisition of a vaccine-specific envelope protein epitope (H5).
  • The Asibi HeLa p6 virus genome showed 29 nucleotide differences encoding 10 amino acid substitutions, including one at NS4B-95, implicated in attenuation.

Conclusions:

  • HeLa cell passage can attenuate specific yellow fever virus strains, impacting virulence and mosquito transmission.
  • The acquisition of the H5 epitope during HeLa passage may contribute to viral attenuation.
  • Not all YF virus strains are amenable to attenuation by HeLa cell passage, highlighting strain-specific characteristics.
  • The NS4B-95 substitution is a potential key factor in the attenuation of YF virus virulence.

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