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Molecular changes associated with adaptation of human influenza A virus in embryonated chicken eggs.
Virology. 2006 Jun 20; 350(1):137-45.V

Abstract

Failure to isolate A/Fujian/411/2002 (H3N2) in embryonated chicken eggs resulted in its absence from the 2003/2004 vaccine. We analyzed the adaptation of this virus in eggs during serial passages in the amniotic then allantoic cavities. Amniotic passage allowed the virus to grow in the allantoic cavity. During adaptation, 6 amino acid substitutions occurred: 4 in HA (G186V, S219F, V226I, V309I) and 2 in NA (E119Q, Q136K). These substitutions allowed binding to SAalpha2,3Gal- and SAalpha2,6Gal-containing receptors, conferred SAalpha2,3Gal specificity, and preserved antigenicity. Two HA substitutions (G186V, V226I) were sufficient to improve growth. Changing 2 NA residues (E119Q, Q136K) did not improve growth, and adaptation did not result in the HA changes H183L, D188Y, and V226A found by others. These findings suggest that viral adaptation in eggs involves multiple strategies. Vaccine manufacture will benefit from increased understanding of adaptation and strategies to improve human influenza A virus replication in eggs.

Authors+Show Affiliations

Division of Virology, Department of Infectious Diseases, Mail Stop 330, St. Jude Children's Research Hospital, and Integrated Program in Biomedical Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16545416

Citation

Widjaja, Linda, et al. "Molecular Changes Associated With Adaptation of Human Influenza a Virus in Embryonated Chicken Eggs." Virology, vol. 350, no. 1, 2006, pp. 137-45.
Widjaja L, Ilyushina N, Webster RG, et al. Molecular changes associated with adaptation of human influenza A virus in embryonated chicken eggs. Virology. 2006;350(1):137-45.
Widjaja, L., Ilyushina, N., Webster, R. G., & Webby, R. J. (2006). Molecular changes associated with adaptation of human influenza A virus in embryonated chicken eggs. Virology, 350(1), 137-45.
Widjaja L, et al. Molecular Changes Associated With Adaptation of Human Influenza a Virus in Embryonated Chicken Eggs. Virology. 2006 Jun 20;350(1):137-45. PubMed PMID: 16545416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular changes associated with adaptation of human influenza A virus in embryonated chicken eggs. AU - Widjaja,Linda, AU - Ilyushina,Natalia, AU - Webster,Robert G, AU - Webby,Richard J, Y1 - 2006/03/20/ PY - 2005/12/02/received PY - 2006/01/04/revised PY - 2006/02/13/accepted PY - 2006/3/21/pubmed PY - 2006/8/3/medline PY - 2006/3/21/entrez SP - 137 EP - 45 JF - Virology JO - Virology VL - 350 IS - 1 N2 - Failure to isolate A/Fujian/411/2002 (H3N2) in embryonated chicken eggs resulted in its absence from the 2003/2004 vaccine. We analyzed the adaptation of this virus in eggs during serial passages in the amniotic then allantoic cavities. Amniotic passage allowed the virus to grow in the allantoic cavity. During adaptation, 6 amino acid substitutions occurred: 4 in HA (G186V, S219F, V226I, V309I) and 2 in NA (E119Q, Q136K). These substitutions allowed binding to SAalpha2,3Gal- and SAalpha2,6Gal-containing receptors, conferred SAalpha2,3Gal specificity, and preserved antigenicity. Two HA substitutions (G186V, V226I) were sufficient to improve growth. Changing 2 NA residues (E119Q, Q136K) did not improve growth, and adaptation did not result in the HA changes H183L, D188Y, and V226A found by others. These findings suggest that viral adaptation in eggs involves multiple strategies. Vaccine manufacture will benefit from increased understanding of adaptation and strategies to improve human influenza A virus replication in eggs. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/16545416/Molecular_changes_associated_with_adaptation_of_human_influenza_A_virus_in_embryonated_chicken_eggs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(06)00111-5 DB - PRIME DP - Unbound Medicine ER -