title: Mutational pattern of influenza B viruses adapted to high growth replication in embryonated eggs.
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.
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, USA. lugovtsev@cber.fda.gov
authors.forename: Vladimir Y
authors.initials: VY
authors.lastname: Lugovtsev
authors.forename: Galina M
authors.initials: GM
authors.lastname: Vodeiko
authors.forename: Roland A
authors.initials: RA
authors.lastname: Levandowski
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000502:physiology; D002642:Chick Embryo; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D004279:DNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D005814:Genes, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics*; D009981:Influenza B virus / Q000235:genetics* / Q000254:growth & development*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D009698:Nucleoproteins / Q000235:genetics; D012367:RNA, Viral / Q000302:isolation & purification / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014779:Virus Replication / Q000235:genetics; D015053:Zygote / Q000821:virology
chemical_list: D000956:Antigens, Viral; D018076:DNA, Complementary; D004279:DNA, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009698:Nucleoproteins; D012367:RNA, Viral