TY - JOUR

T1 - Passage in egg culture is a major cause of apparent positive selection in influenza B hemagglutinin

AU - Gatherer, Derek

PY - 2010/1

Y1 - 2010/1

N2 - Several studies have identified residues apparently under positive selection in influenza B virus hemagglutinin. Host immune evasion is the main mechanism proposed to exert this selection pressure. However, these reports have not considered the culture history of the strains used to calculate positive selection. This article shows that passage of influenza B virus through egg culture is a strong contributory factor to the strength and statistical significance of positive selection on hemagglutinin. Non-synonymous mutations resulting in the loss of the N-glycosylation site at positions 197-199 of hemagglutinin have been positively selected to a far greater degree in egg-cultured strains than in other strains. Once egg-cultured strains are removed from the analysis, positive selection is found to be far weaker, less statistically significant, and more diffusely localized along the protein. Caution should therefore be exercised both in claims for the existence of positive selection in influenza B hemagglutinin, and in attribution of host immune evasion as its cause. The major cause of molecular adaptation in influenza B hemagglutinin proteins may well be laboratory eggs rather than natural hosts. J. Med. Virol. 82:123127, 2010. (C) 2009 Wiley-Liss, Inc.

AB - Several studies have identified residues apparently under positive selection in influenza B virus hemagglutinin. Host immune evasion is the main mechanism proposed to exert this selection pressure. However, these reports have not considered the culture history of the strains used to calculate positive selection. This article shows that passage of influenza B virus through egg culture is a strong contributory factor to the strength and statistical significance of positive selection on hemagglutinin. Non-synonymous mutations resulting in the loss of the N-glycosylation site at positions 197-199 of hemagglutinin have been positively selected to a far greater degree in egg-cultured strains than in other strains. Once egg-cultured strains are removed from the analysis, positive selection is found to be far weaker, less statistically significant, and more diffusely localized along the protein. Caution should therefore be exercised both in claims for the existence of positive selection in influenza B hemagglutinin, and in attribution of host immune evasion as its cause. The major cause of molecular adaptation in influenza B hemagglutinin proteins may well be laboratory eggs rather than natural hosts. J. Med. Virol. 82:123127, 2010. (C) 2009 Wiley-Liss, Inc.

KW - N-glycosylation

KW - immune evasion

KW - non-synonymous substitution

KW - codeml

KW - omega

KW - adaptation

KW - EPIDEMIC ACTIVITY

KW - VIRUS

KW - ADAPTATION

KW - REAPPEARANCE

KW - EVOLUTION

KW - PRESSURE

U2 - 10.1002/jmv.21648

DO - 10.1002/jmv.21648

M3 - Journal article

VL - 82

SP - 123

EP - 127

JO - Journal of Medical Virology

JF - Journal of Medical Virology

SN - 0146-6615

IS - 1

ER -