Loss in Virulence of Yellow Fever Virus Serially Passed in HeLa Cells

Hearn, Henry J.; Soper, William T.; MILLER, WILLIAM

doi:10.3181/00379727-119-30167

Cited by 12 publications

(8 citation statements)

References 1 publication

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“…This observation was later confirmed and extended (Hearn et al, 1965(Hearn et al, , 1966Converse et al, 1971). This paper reports the effects of six HeLa cell passages on other members of the Flaviviridae.…”

Section: Discussionsupporting

confidence: 65%

“…In contrast, the 17D virus for use in YF vaccines was first shown to have a lowered viscerotropism after 176 passages in whole and minced chick embryo (Theiler & Smith, 1937). The original work was later confirmed and extended (Hearn et al, 1965;Converse et al, 1971). Since these studies some 20 years ago very little work has been done on the effect of passage of flaviviruses in HeLa cells.…”

Section: Introductionmentioning

confidence: 53%

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Attenuation of virulence of flaviviruses following passage in HeLa cells

Dunster

Gibson

Stephenson

et al. 1990

Journal of General Virology

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 53%

Attenuation of virulence of flaviviruses following passage in HeLa cells

Dunster

Gibson

Stephenson

et al. 1990

Journal of General Virology

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“…In the 1960s it was reported that wild-type YF strain Asibi could be attenuated by passage in HeLa cells (Hardy, 1963;Hearn et al, 1965Hearn et al, , 1966Converse et al, 1971). Attenuation was seen as decreased viscerotropic (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…As an alternative approach to analysing attenuation/ virulence of YF virus we have repeated and extended the observation that passaging of YF-Asibi virus in HeLa cells resulted in the loss of the ability to cause viscerotropic disease in monkeys (Hardy, 1963;Hearn et al, 1965Hearn et al, , 1966Converse et al, 1971). Reduced virulence was seen after a single passage in HeLa cells and as few as six passages were required to make YF-Asibi virus avirulent for monkeys [0-04 compared to >700000 mouse intracerebral (i.c.)…”

Section: A D T Barrett and Othersmentioning

confidence: 99%

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

Barrett

Monath

Cropp

et al. 1990

Journal of General Virology

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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 YFAsibi-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-typespecific, recognized YF-Asibi-LP virus but not YFAsibi-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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“…This property, described first for YF by Theiler in 1930, can be modified by passage of the virus. Serial passage in mouse brain increases neurovirulence (Theiler, 1951;Meers, 1959;reviewed in Schlesinger, 1980), whereas passage in cell culture has been associated with reduction of virulence properties (Hardy, 1963;Hearn et al, 1965Hearn et al, , 1966Converse et al, 1971;Barrett et al, 1990). Although *Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

Replication of yellow fever virus in the mouse central nervous system: comparison of neuroadapted and non-neuroadapted virus and partial sequence analysis of the neuroadapted strain

Schlesinger

Chapman

Nestorowicz

et al. 1996

Journal of General Virology

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Serial passage of yellow fever virus (YF17D) in mouse brain enhances neurovirulence, causing a reduction in survival time after intracerebral inoculation of adult mice. To study the biological and genetic basis for this phenomenon, we compared neurovirulence properties of the neuroadapted Porterfield strain (PYF) to a YF17D strain generated from a full-length YF cDNA template (YF5.2iv). Adult mice were infected by olfactory bulb inoculation, which results in widespread distribution of virus throughout the central nervous system. Although PYF and YF5.2iv spread rapidly throughout the neuraxis, maximal titres of PYF in the brain and spinal cord were 1000-to 10 000-fold higher than those of YF5.2iv. Paralysis and death occurred earlier with the PYF strain. Several cDNA clones of the E/NS1 region of the PYF strain were sequenced. Three predicted amino acid changes were consistently observed in the envelope protein of the PYF strain compared to YF5.2iv. Common substitutions were also identified in NS1 and NS2A. The potential contribution of these genetic differences to neurovirulence was evaluated by generating recombinant, intertypie PYF/YFS.2iv viruses. Physical signs of disease and mean spinal cord titres after inoculation of one recombinant were not different from the YF5.2iv parent. Our data indicate that PYF and YF5.2iv differ significantly in their virulence properties, however, common amino acid substitutions in the E/NS1 region of the PYF strain do not determine its enhanced neurovirulence. Other regions of the viral genome may contribute dominant effects on the virulence properties of the PYF strain.

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Loss in Virulence of Yellow Fever Virus Serially Passed in HeLa Cells

Cited by 12 publications

References 1 publication

Attenuation of virulence of flaviviruses following passage in HeLa cells

Attenuation of virulence of flaviviruses following passage in HeLa cells

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

Replication of yellow fever virus in the mouse central nervous system: comparison of neuroadapted and non-neuroadapted virus and partial sequence analysis of the neuroadapted strain

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