Sequence analysis of the haemagglutinin (HA) of influenza A (H1N1) viruses present in clinical material and comparison with the HA of laboratory-derived virus.
We used the polymerase chain reaction to amplify the HA1 coding region of influenza A (H1N1) viruses present in clinical material from recent cases of influenza in the U.K. Previously, we have demonstrated that isolation of human influenza viruses in embryonated hens' eggs selects variants which have amino acid substitutions in their haemagglutinin (HA) clustering around the receptor-binding site. Such egg-selected variants are often antigenically distinct from each other and from corresponding viruses isolated on mammalian cells. Since in general the virus used for vaccine production is an egg-adapted virus, it is important to determine the extent to which these variants are present in the natural virus which causes disease in man. To achieve this, amplified products from clinical material were cloned and many individual clones sequenced. Our results indicate that the HA of the naturally occurring virus is relatively homogeneous and represented by virus isolated in the laboratory on MDCK cells, whereas the variants isolated in eggs are present only at low levels in clinical material.
National Institute for Biological Standards and Control, Hertfordshire, U.K.
J S
JS
Robertson
C
C
Nicolson
J S
JS
Bootman
D
D
Major
E W
EW
Robertson
J M
JM
Wood
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002642:Chick Embryo; D003001:Cloning, Molecular; D004279:DNA, Viral; D014644:Genetic Variation; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics*; D053118:Influenza A Virus, H1N1 Subtype; D009980:Influenza A virus / Q000235:genetics*; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment
D004279:DNA, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral