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Virus Res. 2005 May;109(2):149-57. Epub 2004 Dec 29.

Mutational pattern of influenza B viruses adapted to high growth replication in embryonated eggs.

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  • 1Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, USA. lugovtsev@cber.fda.gov

Abstract

Improved replication of influenza viruses in embryonated chicken eggs (CE) permits increased vaccine production and availability. We investigated the growth properties of influenza B viruses in relation to specific mutations occurring after serial passage in CE. In serial passage experiments yielding high growth variants of B/Victoria/504/2000, mutations predicted to alter amino acid (AA) composition occurred only near the receptor-binding pocket of the hemagglutinins (HA) and in no other genes. Two B/Victoria/504/2000 high growth variants had the same AA substitutions in HA (R162M and D196Y), but the higher yield variant had a third substitution (G141E), which also altered antigenic characteristics. In a serial passage experiment yielding a high growth variant of B/Hong Kong/330/2001, mutations predicted to alter AA composition occurred only in PB2 and NP in domains predicted to relate to RNP formation and function. Our results indicate that adaptation of influenza B viruses to high-yield replication by serial passage in CE requires few mutations either in internal or external genes. Specific modifications of genes or a combination of genes could be used to optimize or create influenza B viruses for specific growth substrates.

[PubMed - indexed for MEDLINE]
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