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Genetic bases of the temperature-sensitive phenotype of a master donor virus used in live attenuated influenza vaccines: A/Leningrad/134/17/57 (H2N2).

Identifieur interne : 000C60 ( Main/Exploration ); précédent : 000C59; suivant : 000C61

Genetic bases of the temperature-sensitive phenotype of a master donor virus used in live attenuated influenza vaccines: A/Leningrad/134/17/57 (H2N2).

Auteurs : Irina Isakova-Sivak [États-Unis] ; Li-Mei Chen ; Yumiko Matsuoka ; J Theo M. Voeten ; Irina Kiseleva ; Jacco G M. Heldens ; Han Van Den Bosch ; Alexander Klimov ; Larisa Rudenko ; Nancy J. Cox ; Ruben O. Donis

Source :

RBID : pubmed:21315402

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English descriptors

Abstract

Trivalent live attenuated influenza vaccines whose type A components are based on cold-adapted A/Leningrad/134/17/57 (H2N2) (caLen17) master donor virus (MDV) have been successfully used in Russia for decades to control influenza. The vaccine virus comprises hemagglutinin and neuraminidase genes from the circulating viruses and the remaining six genes from the MDV. The latter confer temperature-sensitive (ts) and attenuated (att) phenotypes. The ts phenotype of the vaccine virus is a critical biological determinant of attenuation of virulence. We developed a plasmid-based reverse genetics system for MDV caLen17 to study the genetic basis of its ts phenotype. Mutations in the polymerase proteins PB1 and PB2 played a crucial role in the ts phenotype of MDV caLen17. In addition, we show that caLen17-specific ts mutations could impart the ts phenotype to the divergent PR8 virus, suggesting the feasibility of transferring the ts phenotype to new viruses of interest for vaccine development.

DOI: 10.1016/j.virol.2011.01.004
PubMed: 21315402


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<term>Influenza A Virus, H2N2 Subtype (growth & development)</term>
<term>Influenza Vaccines (genetics)</term>
<term>Mutation, Missense</term>
<term>Phenotype</term>
<term>Plasmids</term>
<term>RNA Replicase (genetics)</term>
<term>RNA Replicase (metabolism)</term>
<term>Russia</term>
<term>Temperature</term>
<term>Vaccines, Attenuated (genetics)</term>
<term>Viral Plaque Assay</term>
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<term>Viral Proteins (metabolism)</term>
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<term>Méthode des plages virales</term>
<term>Phénotype</term>
<term>Plasmides</term>
<term>Protéines virales (génétique)</term>
<term>Protéines virales (métabolisme)</term>
<term>RNA replicase (génétique)</term>
<term>RNA replicase (métabolisme)</term>
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<term>Sous-type H2N2 du virus de la grippe A (croissance et développement)</term>
<term>Sous-type H2N2 du virus de la grippe A (génétique)</term>
<term>Température</term>
<term>Vaccins antigrippaux (génétique)</term>
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<div type="abstract" xml:lang="en">Trivalent live attenuated influenza vaccines whose type A components are based on cold-adapted A/Leningrad/134/17/57 (H2N2) (caLen17) master donor virus (MDV) have been successfully used in Russia for decades to control influenza. The vaccine virus comprises hemagglutinin and neuraminidase genes from the circulating viruses and the remaining six genes from the MDV. The latter confer temperature-sensitive (ts) and attenuated (att) phenotypes. The ts phenotype of the vaccine virus is a critical biological determinant of attenuation of virulence. We developed a plasmid-based reverse genetics system for MDV caLen17 to study the genetic basis of its ts phenotype. Mutations in the polymerase proteins PB1 and PB2 played a crucial role in the ts phenotype of MDV caLen17. In addition, we show that caLen17-specific ts mutations could impart the ts phenotype to the divergent PR8 virus, suggesting the feasibility of transferring the ts phenotype to new viruses of interest for vaccine development.</div>
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